176 results on '"Niswander L"'
Search Results
2. Long-acting PGE2 and Lisinopril Mitigate H-ARS
- Author
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Saunders, J., primary, Niswander, L. M., additional, McGrath, K. E., additional, Koniski, A., additional, Catherman, S. C., additional, Ture, S. K., additional, Medhora, M., additional, Kingsley, P. D., additional, Calvi, L. M., additional, Williams, J. P., additional, Morrell, C. N., additional, and Palis, J., additional more...
- Published
- 2021
- Full Text
- View/download PDF
Catalog
3. Neural-Tube Defects
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Pyrgaki, C., primary and Niswander, L., additional
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- 2013
- Full Text
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4. Contributors
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Akshoomoff, N., primary, Bauer, P.J., additional, Beltz, A.M., additional, Berenbaum, S.A., additional, Blakemore, J.E.O., additional, Bowman, A.B., additional, Bramen, J.E., additional, Brooks-Kayal, A.R., additional, Casey, B.J., additional, Cohen, M.M., additional, Colby, J.B., additional, Colonnese, M., additional, Cordeaux, C., additional, Cubells, J.F., additional, Davis, E.P., additional, Decety, J., additional, Ess, K.C., additional, Feldman, D.E., additional, Fernandez, L., additional, Fitch, R.H., additional, Fox, N.A., additional, Franklin, N., additional, Gillespie, D.C., additional, Gunnar, M.R., additional, Gweon, H., additional, Hagerman, R.J., additional, Haist, F., additional, Hughes, C., additional, Johnson, M.H., additional, Johnson, S.P., additional, Kano, M., additional, Khazipov, R., additional, Kim, S.-J., additional, King, A.J., additional, Kumar, K.K., additional, Lahat, A., additional, Lany, J., additional, Leigh, M.J., additional, Lein, P.J., additional, Lepousez, G., additional, Lewis, M., additional, Lledo, P.-M., additional, Michalska, K.J., additional, Miller, M.W., additional, Minlebaev, M., additional, Molnár, Z., additional, Mooney, S.M., additional, Moreno-De-Luca, D., additional, Muller, D., additional, Nelson, C.A., additional, Nikonenko, I., additional, Niswander, L., additional, O'Hare, E.D., additional, Pelphrey, K., additional, Persico, A.M., additional, Polley, D.B., additional, Posner, M.I., additional, Pyrgaki, C., additional, Reiter, L.T., additional, Righi, G., additional, Rothbart, M.K., additional, Rubenstein, E., additional, Rueda, M.R., additional, Saffran, J.R., additional, Sanchez, J.T., additional, Saxe, R., additional, Seery, A.M., additional, Seidl, A.H., additional, Sherr, E.H., additional, Shulz, D.E., additional, Sowell, E.R., additional, Stanford, T.R., additional, Stein, B.E., additional, Stiles, J., additional, Summar, K.L., additional, Tager-Flusberg, H., additional, Thomas, A.X., additional, Tirrell, J., additional, Urraca, N., additional, Veenstra-VanderWeele, J., additional, Voos, A., additional, Wang, Y., additional, and Watanabe, M., additional more...
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- 2013
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5. Zic2 is required for enteric nervous system development and neurite outgrowth: a mouse model of enteric hyperplasia and dysplasia
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Zhang, Y. and Niswander, L.
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- 2013
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6. Expression of a constitutively active type I BMP receptor using a retroviral vector promotes the development of adrenergic cells in neural crest cultures
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Varley, J.E., McPherson, C.E., Zou, H., Niswander, L., and Maxwell, G.D.
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Morphogenesis -- Research ,Bones -- Genetic aspects ,Cell receptors -- Research ,Retroviruses -- Genetic aspects ,Neural receptors -- Research ,Biological sciences - Abstract
Previous work has demonstrated that the bone morphogenetic proteins (BMP)-2, BMP-4, and BMP-7 can promote the development of tyrosine hydroxylase (TH)-positive and catecholamine-positive cells in quail trunk neural crest cultures. In the present work, we showed that mRNA for the type I bone morphogenetic protein receptor IA (BMPR-IA) was present in neural crest cells grown in the absence or presence of BMP-4. We have used a replication-competent avian retrovirus to express a constitutively active form of BMPR-IA in neural crest cells in culture. Cultures grown in the absence of BMP-4 and infected with retrovirus containing a construct encoding this activated BMPR-IA developed five times more TH-immunoreactive and catecholamine-positive cells than uninfected control cultures or cultures infected with virus bearing the wild-type BMPR-IA cDNA. The number of TH-positive cells which developed was dependent on the concentration of virus bearing the activated receptor cDNA used in the experiments. Most TH-positive cells which developed also contained viral p19 protein. Total cell number was not affected by infection with the virus containing the activated receptor construct. The effect of the activated receptor was phenotype-specific since infection with the virus bearing the activated receptor cDNA did not alter the number or morphology of microtubule-associated protein (MAP)2-immunoreactive cells, which are distinct from the TH-positive cell population. These findings are consistent with the observation that MAP2-positive cells are not affected by the presence of BMP-4. Taken together, these results suggest that activity of BMPR-IA is an important element in promoting the development of the adrenergic phenotype in neural crest cultures. Key Words: bone morphogenetic protein; retroviral construct; neural crest; adrenergic; neural development. more...
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- 1998
7. S84 LINKS BETWEEN LUNG DEVELOPMENT AND DISEASE
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Dean, C. H., Hidalgo, N., and Niswander, L. A.
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- 2004
8. Long-acting PGE2 and Lisinopril Mitigate H-ARS.
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Saunders II, J., Niswander, L. M., McGrath, K. E., Koniski, A., Catherman, S. C., Ture, S. K., Medhora, M., Kingsley, P. D., Calvi, L. M., Williams, J. P., Morrell, C. N., and Palis, J.
- Subjects
RADIATION injuries ,ANGIOTENSIN converting enzyme ,LISINOPRIL ,RADIATION exposure ,HEMORRHAGE ,BONE marrow - Abstract
Thrombocytopenia is a major complication in hematopoietic-acute radiation syndrome (H-ARS) that increases the risk of mortality from uncontrolled hemorrhage. There is a great demand for new therapies to improve survival and mitigate bleeding in H-ARS. Thrombopoiesis requires interactions between megakaryocytes (MKs) and endothelial cells. 16, 16-dimethyl prostaglandin E
2 (dmPGE2 ), a longer-acting analogue of PGE2 , promotes hematopoietic recovery after total-body irradiation (TBI), and various angiotensin-converting enzyme (ACE) inhibitors mitigate endothelial injury after radiation exposure. Here, we tested a combination therapy of dmPGE2 and lisinopril to mitigate thrombocytopenia in murine models of H-ARS following TBI. After 7.75 Gy TBI, dmPGE2 and lisinopril each increased survival relative to vehicle controls. Importantly, combined dmPGE2 and lisinopril therapy enhanced survival greater than either individual agent. Studies performed after 4 Gy TBI revealed reduced numbers of marrow MKs and circulating platelets. In addition, sublethal TBI induced abnormalities both in MK maturation and in in vitro and in vivo platelet function. dmPGE2 , alone and in combination with lisinopril, improved recovery of marrow MKs and peripheral platelets. Finally, sublethal TBI transiently reduced the number of marrow Lin–CD45–CD31+ Sca-1– sinusoidal endothelial cells, while combined dmPGE2 and lisinopril treatment, but not single-agent treatment, accelerated their recovery. Taken together, these data support the concept that combined dmPGE2 and lisinopril therapy improves thrombocytopenia and survival by promoting recovery of the MK lineage, as well as the MK niche, in the setting of H-ARS. [ABSTRACT FROM AUTHOR] more...- Published
- 2021
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9. Msx and Dlx in Feather Development
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Rouzankina, I., Zikherman, J., and Niswander, L. A.
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Homeobox genes -- Physiological aspects ,Feathers -- Genetic aspects ,Animal genetics -- Research ,Biological sciences - Abstract
Homeobox-containing genes Msx and Dlx are involved in development of various tissues and organs. The developing feather array is a convenient system for studying cellular and molecular interactions as well as cell fate determination and pattern formation. During feather bud development, Msx1, Msx2, and Dlx5 genes are expressed in the buds. Their expression is regulated by BMP and altered expression of Msx1,2 causes loss of buds, whereas misexpression of Dlx causes bud fusions and loss. Preliminary analysis suggests that BMP and Msx may affect feather bud formation through the inhibition of Lef. Dlx genes act through a different mechanism which is induction of NCAM. At present we are working on identifying other target molecules and developing a model of how Msx and Dlx mediate feather morphogenesis. more...
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- 2001
10. Mechanism of Epidermal Growth Factor Action in Avian Skin Development
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Atit, R. P. and Niswander, L. A.
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Morphogenesis -- Physiological aspects ,Epidermal growth factor -- Physiological aspects ,Skin -- Physiological aspects ,Developmental biology -- Research ,Biological sciences - Abstract
The developing avian feather bud is an established model that facilitates the study of two major processes in development, cell fate determination, and pattern formation. The feather tract is a sequentially generated and reiterated pattern. The buds form in a hexagonal array and each bud is separated from its neighbors by an interbud region of smooth skin. Morphogenesis of the feather bud is a coordinated subdivision of the epidermis and dermis into bud versus interbud fates. Perturbations in cell fate decisions or cellular processes such as proliferation, migration, and cell-cell communication result in obvious changes to the pattern. Experiments in the 1960s found that epidermal growth factor (EGF) stimulates epithelial cell proliferation and perturbs bud development in explants of avian embryonic skin. We have confirmed and extended these results to determine the mechanism of action. In the presence of EGF, the entire epidermis proliferates rapidly and there is a loss of feather bud formation. Any existing feather bud primordia also disappear after 2 days in culture. The inhibition of feather buds also correlate with the loss of feather markers. EGF is expressed in the interbud regions of embryonic skin. Exposure to excess EGF may lead to conversion of the bud to the interbud fate. Alternatively, EGF may prevent bud formation by enhancing epidermal cell proliferation and diminishing mesenchymal proliferation or by disrupting the communication between these tissues. Current studies will differentiate between these possibilites and elucidate the mechanism of EGF action in feather bud development. more...
- Published
- 2001
11. Limb Development in the Short-Tailed Fruit Bat Carollia perspicillata
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Weatherbee, S. D., Cretekos, C. J., Behringer, R., Rasweiler, J. J. IV, and Niswander, L. A.
- Subjects
Developmental biology -- Research ,Cell research -- Analysis ,Vertebrates -- Physiological aspects ,Fruit bats ,Biological sciences - Abstract
Developmental biology strives to decipher how a single cell gives rise to a complex, multicellular organism. Most animals share specific families of genes that regulate major aspects of body pattern. At the same time, biologists recognize that the ontogenic path varies from species to species. Thus, dissecting the molecular genetic mechanisms underlying development in different species should elucidate common principles of development but may also shed some light on the evolution of diverse animal forms. Our labs share an interest in vertebrate limb development and while most of this research in this field has been limited to the chick and mouse, we would like to broaden the scope of this work to include bats. Why study bats? One of the most productive adaptations of the vertebrate limb has been for flight. Bats are the most successful mammals, contributing close to one-quarter of all mammalian species. Unlike bird wings, the lifting surface of bat wings is composed of a membrane that extends between the forelimb digits as well as between the limbs and body wall. In addition, bat limbs demonstrate several other unique characteristics including elongated zeugopod and autopod skeletal elements. We have begun cloning and characterizing the expression of a number of genes from Carollia, with particular interest in those known to regulate limb growth, patterning, or cell death in order to better understand the unique aspects of bat limb development. more...
- Published
- 2001
12. Bone Morphogenetic Protein (BMP) Control of Wnt Ligands, Secreted Inhibitors, and Receptors during Neural Development
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Chesnutt, C. R., Brown, A. M. C., and Niswander, L. A.
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Bone morphogenetic proteins -- Physiological aspects ,Neural networks -- Physiological aspects ,Neural tube -- Growth ,Biological sciences - Abstract
BMPs have been shown in our lab and others to regulate patterning along the dorsoventral (DV) axis of the developing neural tube. Wnt genes, their receptors, and secreted inhibitors display discrete and overlapping domains of expression along this DV axis. To determine the effect of BMP signaling on Wnt pathway components we altered BMP signaling. Misexpression of a constitutively activated BMP receptor, which causes dorsalization of the neural tube, expanded dorsal Wnts ventrally and reduced ventrally restricted Wnts to a smaller ventral domain. Conversely, misexpression of noggin, a secreted BMP inhibitor, diminishes dorsal Wnts while expanding the dorsal border of normally ventrally localized Wnts. Thus, BMPs appear to positively regulate dorsally restricted Wnt members while negatively regulating the dorsal border of ventral members. We are currently exploring the potential role these Wnt genes may have in dorsoventral patterning of the neural tube. These studies include misexpression of a secreted inhibitor of Wnt ligands and further downstream components, as well as inhibitors of both the BMP and Wnt pathways. more...
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- 2001
13. Chapter 27 - Neural-Tube Defects
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Pyrgaki, C. and Niswander, L.
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- 2013
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14. ALC ((a)under-bardjacent to (L)under-barMX1 in (c)under-barhick) is a novel dorsal limb mesenchyme marker
- Author
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Holmes, G., Crooijmans, R.P.M.A., Groenen, M.A.M., and Niswander, L.
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wnt7a ,chick ,expression ,WIAS ,lmx1 ,Fokkerij en Genomica ,Animal Breeding and Genomics ,vertebrate limb ,pattern ,transcription factor - Abstract
During dorsal¿ventral (DV) patterning of the vertebrate limb, WNT7A is expressed in dorsal limb ectoderm and activates the expression of LMX1 (in chick; Lmx1b in mouse) in dorsal limb mesenchyme, resulting in the appropriate development of dorsal cell fates. These two genes are the only known factors involved in directing dorsal patterning and the molecular events that link these two factors or that occur downstream of LMX1/1b are unknown. We have isolated a novel chick transcript, ALC (adjacent to LMX1 in chick). ALC is located 5.3 kb from the 5¿ end of LMX1 and is transcribed in the opposite direction. It is expressed in a sub-set of tissues expressing LMX1, most notably in the dorsal mesenchyme of the limb, and thus is the second gene discovered with such a distribution in the limb. Misexpression studies with viral constructs show that ALC is downstream of WNT7A but not of LMX1. ALC shows no homology to known genes and its function remains to be determined. However, similarly placed transcripts occur in the human and mouse genomes, and we demonstrate that a mouse transcript is also expressed in dorsal limb mesenchyme more...
- Published
- 2003
15. Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma
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Parker, J. J., primary, Dionne, K. R., additional, Massarwa, R., additional, Klaassen, M., additional, Foreman, N. K., additional, Niswander, L., additional, Canoll, P., additional, Kleinschmidt-DeMasters, B. K., additional, and Waziri, A., additional more...
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- 2013
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16. LAB-ANGIOGENESIS AND INVASION
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Proescholdt, M. A., primary, Merrill, M. J., additional, Stoerr, E.-M., additional, Lohmeier, A., additional, Brawanski, A., additional, Sim, H., additional, Hu, B., additional, Pineda, C. A., additional, Yoon, S.-O., additional, Viapiano, M. S., additional, Rajappa, P., additional, Cobb, W. S., additional, Huang, Y., additional, Lyden, D. C., additional, Bromberg, J., additional, Greenfield, J. P., additional, Li, M., additional, Mukasa, A., additional, Inda, M. d.-M., additional, Zhang, J., additional, Chin, L., additional, Cavenee, W., additional, Furnari, F., additional, Zheng, P.-P., additional, van der Weiden, M., additional, van der Spek, P. J., additional, Vincent, A. J., additional, Kros, J. M., additional, Fathallah-Shaykh, H. M., additional, Saut, O., additional, Lagaert, J.-B., additional, Colin, T., additional, Araysi, L., additional, Tang, Z., additional, Duck, K. A., additional, Ponnuru, P., additional, Neely, E. B., additional, Connor, J. R., additional, Esencay, M., additional, Gonzalez, P., additional, Gaziel, A., additional, Safraz, Y., additional, Mira, H., additional, Hernando, E., additional, Zagzag, D., additional, McDermott, R. A., additional, Ulasov, I., additional, Kaverina, N., additional, Gabikian, P., additional, Lesniak, M., additional, Iranmahboob, A., additional, Haber, M., additional, Fatterpekar, G., additional, Raz, E., additional, Placantonakis, D., additional, Eoli, M., additional, Rabascio, C., additional, Cuppini, L., additional, Anghileri, E., additional, Pellegatta, S., additional, Calleri, A., additional, Mancuso, P., additional, Porrati, P., additional, Bertolini, F., additional, Finocchiaro, G., additional, Seals, D. F., additional, Burger, K. L., additional, Gibo, D. M., additional, Debinski, W., additional, Tran, N. L., additional, Tuncali, S., additional, Kloss, J., additional, Yang, Z., additional, Schumacher, C. A., additional, Diegel, C., additional, Ross, J. T., additional, Williams, B. O., additional, Eschbacher, J. M., additional, Loftus, J. C., additional, Whiteman, M., additional, Dombovy-Johnson, M., additional, Vangellow, A., additional, Liu, Y., additional, Carson-Walter, E., additional, Walter, K. A., additional, Walter, K., additional, Cortes-Santiago, N., additional, Gabrusiewicz, K., additional, Liu, D., additional, Hossain, M. B., additional, Gumin, J., additional, Fan, X., additional, Conrad, C., additional, Aldape, K., additional, Gilbert, M., additional, Raghunathan, A., additional, Yung, W. K. A., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Bae, E., additional, Huang, P., additional, Burgett, M., additional, Muller-Greven, G., additional, Kar, N., additional, Gladson, C. L., additional, Engler, J. R., additional, Robinson, A. E., additional, Molinaro, A., additional, Phillips, J. J., additional, Zadeh, G., additional, Burrell, K., additional, Hill, R., additional, Piao, Y., additional, Liang, J., additional, Henry, V., additional, Holmes, L., additional, Sulman, E., additional, deGroot, J. F., additional, de Groot, J. F., additional, Rong, W., additional, Funato, K., additional, Georgala, P., additional, Shimizu, F., additional, Droms, L., additional, Tabar, V., additional, Parker, J. J., additional, Dionne, K. R., additional, Massarwa, R., additional, Klaassen, M., additional, Foreman, N. K., additional, Niswander, L., additional, Canoll, P., additional, Kleinschmidt-DeMasters, B. K., additional, and Waziri, A., additional more...
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- 2012
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17. ANGIOGENESIS AND INVASION
- Author
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Hu, Y.-L., primary, De Lay, M., additional, Rose, S. D., additional, Carbonell, W. S., additional, Aghi, M. K., additional, Hu, Y.-L., additional, Paquette, J., additional, Tokuyasu, T., additional, Tsao, S., additional, Chaumeil, M., additional, Ronen, S., additional, Matlaf, L. A., additional, Soroceanu, L., additional, Cobbs, C., additional, Matlaf, L., additional, Harkins, L., additional, Garzon-Muvdi, T., additional, Rhys, C. a., additional, Smith, C., additional, Kim, D.-H., additional, Kone, L., additional, Farber, H., additional, An, S., additional, Levchenko, A., additional, Quinones-Hinojosa, A., additional, Lemke, D., additional, Pfenning, P.-N., additional, Sahm, F., additional, Klein, A.-C., additional, Kempf, T., additional, Schnolzer, M., additional, Platten, M., additional, Wick, W., additional, Smith, S. J., additional, Rahman, R., additional, Rahman, C., additional, Barrow, J., additional, Macarthur, D., additional, Rose, F., additional, Grundy, R. G., additional, Kaley, T. J., additional, Huse, J., additional, Karimi, S., additional, Rosenblum, M., additional, Omuro, A., additional, DeAngelis, L. M., additional, de Groot, J. F., additional, Kong, L.-Y., additional, Wei, J., additional, Wang, T., additional, Piao, Y., additional, Liang, J., additional, Fuller, G. N., additional, Qiao, W., additional, Heimberger, A. B., additional, Jhaveri, N., additional, Cho, H., additional, Torres, S., additional, Wang, W., additional, Schonthal, A., additional, Petasis, N., additional, Louie, S. G., additional, Hofman, F., additional, Chen, T. C., additional, Yamada, R., additional, Sumual, S., additional, Buljan, V., additional, Bennett, M. R., additional, McDonald, K. L., additional, Weiler, M., additional, Thiepold, A.-L., additional, Jestaedt, L., additional, Gronych, J., additional, Dittmann, L. M., additional, Jugold, M., additional, Kosch, M., additional, Combs, S. E., additional, von Deimling, A., additional, Weller, M., additional, Bendszus, M., additional, Kwiatkowska, A., additional, Paulino, V., additional, Tran, N. L., additional, Symons, M., additional, Stockham, A. L., additional, Borden, E., additional, Peereboom, D., additional, Hu, Y., additional, Chaturbedi, A., additional, Hamamura, M., additional, Mark, E., additional, Zhou, Y.-H., additional, Abbadi, S., additional, Guerrero-Cazares, H., additional, Pistollato, F., additional, Smith, C. L., additional, Ruff, W., additional, Puppa, A. D., additional, Basso, G., additional, Monje, M., additional, Freret, M. E., additional, Masek, M., additional, Fisher, P. G., additional, Haddix, T., additional, Vogel, H., additional, Kijima, N., additional, Hosen, N., additional, Kagawa, N., additional, Hashimoto, N., additional, Fujimoto, Y., additional, Kinoshita, M., additional, Sugiyama, H., additional, Yoshimine, T., additional, Anneke, N., additional, Bob, H., additional, Pieter, W., additional, Arend, H., additional, William, L., additional, Eoli, M., additional, Calleri, A., additional, Cuppini, L., additional, Anghileri, E., additional, Pellegatta, S., additional, Prodi, E., additional, Bruzzone, M. G., additional, Bertolini, F., additional, Finocchiaro, G., additional, Zhu, D., additional, Hunter, S. B., additional, Vertino, P. M., additional, Van Meir, E. G., additional, Cork, S. M., additional, Kaur, B., additional, Cooper, L., additional, Saltz, J. H., additional, Sandberg, E. M., additional, Burrell, K., additional, Hill, R., additional, Zadeh, G., additional, Parker, J. J., additional, Dionne, K., additional, Massarwa, R., additional, Klaassen, M., additional, Niswander, L., additional, Kleinschmidt-DeMasters, B. K., additional, Waziri, A., additional, Jalali, S., additional, Wataya, T., additional, Salehi, F., additional, Croul, S., additional, Gentili, F., additional, Foltz, W., additional, Lee, J.-I., additional, Agnihorti, S., additional, Menard, C., additional, Chung, C., additional, Schonthal, A. H., additional, Hofman, F. M., additional, Elena, P., additional, Faivre, G., additional, Demopoulos, A., additional, Taillibert, S., additional, Kirsch, M., additional, Martin, K. D., additional, Bertram, A., additional, uckermann, O., additional, Leipnitz, E., additional, Weigel, P., additional, Temme, A., additional, Schackert, G., additional, Geiger, K., additional, Gerstner, E., additional, Jennings, D., additional, Chi, A. S., additional, Plotkin, S., additional, Kwon, S. J., additional, Pinho, M., additional, Polaskova, P., additional, Batchelor, T. T., additional, Sorensen, A. G., additional, Hossain, M. B., additional, Gururaj, A. E., additional, Cortes-Santiago, N., additional, Gabrusiewicz, K., additional, Yung, W. K. A., additional, Fueyo, J., additional, Gomez-Manzano, C., additional, Gil, O. D., additional, Noticewala, S., additional, Ivkovic, S., additional, Esencay, M., additional, Zagzagg, D., additional, Rosenfeld, S., additional, Bruce, J. N., additional, Canoll, P., additional, Chang, J. H., additional, Seol, H. J., additional, Weeks, A., additional, Smith, C. A., additional, Rutka, J. T., additional, Georges, J., additional, Samuelson, G., additional, Misra, A., additional, Joy, A., additional, Huang, Y., additional, McQuilkin, M., additional, Yoshihiro, A., additional, Carpenter, D., additional, Butler, L., additional, Feuerstein, B., additional, Murphy, S. F., additional, Vaghaiwalla, T., additional, Wotoczek-Obadia, M., additional, Albright, R., additional, Mack, D., additional, Lawn, S., additional, Henderson, F., additional, Jung, M., additional, Dakshanamurthy, S., additional, Brown, M., additional, Forsyth, P., additional, Brem, S., additional, Sadr, M. S., additional, Maret, D., additional, Sadr, E. S., additional, Siu, V., additional, Alshami, J., additional, Trinh, G., additional, Denault, J.-S., additional, Faury, D., additional, Jabado, N., additional, Nantel, A., additional, and Del Maestro, R., additional more...
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- 2011
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18. Effect of modulation of MET with the small molecule inhibitor PF-04217903 on osteosarcoma metastasis in vivo.
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Niswander, L. M., primary, Guenther, L. M., additional, Mendoza, A., additional, Khanna, C., additional, Christensen, J. G., additional, Helman, L. J., additional, and Kim, S., additional
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- 2010
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19. The correlated evolution of Runx2 tandem repeats, transcriptional activity, and facial length in Carnivora
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Sears, K. E., primary, Goswami, A., additional, Flynn, J. J., additional, and Niswander, L. A., additional
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- 2007
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20. The surface ectoderm is essential for nephric duct formation in intermediate mesoderm
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Obara-Ishihara, T., primary, Kuhlman, J., additional, Niswander, L., additional, and Herzlinger, D., additional
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- 1999
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21. Delta-1 negatively regulates the transition from prehypertrophic to hypertrophic chondrocytes during cartilage formation
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Crowe, R., primary, Zikherman, J., additional, and Niswander, L., additional
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- 1999
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22. BMPs negatively regulate structure and function of the limb apical ectodermal ridge
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Pizette, S., primary and Niswander, L., additional
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- 1999
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23. Involvement of T-box genes Tbx2-Tbx5 in vertebrate limb specification and development
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Gibson-Brown, J.J., primary, Agulnik, S.I., additional, Silver, L.M., additional, Niswander, L., additional, and Papaioannou, V.E., additional
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- 1998
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24. A new role for Notch and Delta in cell fate decisions: patterning the feather array
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Crowe, R., primary, Henrique, D., additional, Ish-Horowicz, D., additional, and Niswander, L., additional
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- 1998
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25. Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb
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Yang, Y., primary, Drossopoulou, G., additional, Chuang, P.T., additional, Duprez, D., additional, Marti, E., additional, Bumcrot, D., additional, Vargesson, N., additional, Clarke, J., additional, Niswander, L., additional, McMahon, A., additional, and Tickle, C., additional more...
- Published
- 1997
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26. Limb deformity proteins: role in mesodermal induction of the apical ectodermal ridge
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Kuhlman, J., primary and Niswander, L., additional
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- 1997
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27. FGF-4 regulates expression of Evx-1 in the developing mouse limb
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Niswander, L., primary and Martin, G.R., additional
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- 1993
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28. Molecular genetic studies of the Cdc7 protein kinase and induced mutagenesis in yeast.
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Hollingsworth, R E, primary, Ostroff, R M, additional, Klein, M B, additional, Niswander, L A, additional, and Sclafani, R A, additional
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- 1992
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29. Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse
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Niswander, L., primary and Martin, G.R., additional
- Published
- 1992
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30. BMP controls proximodistal outgrowth, via induction of the apical ectodermal ridge, and dorsoventral patterning in the vertebrate limb.
- Author
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Pizette, S, Abate-Shen, C, and Niswander, L
- Abstract
Dorsoventral (DV) patterning of the vertebrate limb requires the function of the transcription factor Engrailed 1 (EN1) in the ventral ectoderm. EN1 restricts, to the dorsal half of the limb, the expression of the two genes known to specify dorsal pattern. Limb growth along the proximodistal (PD) axis is controlled by the apical ectodermal ridge (AER), a specialized epithelium that forms at the distal junction between dorsal and ventral ectoderm. Using retroviral-mediated misexpression of the bone morphogenetic protein (BMP) antagonist Noggin or an activated form of the BMP receptor in the chick limb, we demonstrate that BMP plays a key role in both DV patterning and AER induction. Thus, the DV and PD axes are linked by a common signal. Loss and gain of BMP function experiments show that BMP signaling is both necessary and sufficient to regulate EN1 expression, and consequently DV patterning. Our results also indicate that BMPs are required during induction of the AER. Manipulation of BMP signaling results in either disruptions in the endogenous AER, leading to absent or severely truncated limbs or the formation of ectopic AERs that can direct outgrowth. Moreover, BMP controls the expression of the MSX transcription factors, and our results suggest that MSX acts downstream of BMP in AER induction. We propose that the BMP signal bifurcates at the level of EN1 and MSX to mediate differentially DV patterning and AER induction, respectively. more...
- Published
- 2001
31. Organization of a multifunctional protein in pyrimidine biosynthesis. A domain hypersensitive to proteolysis
- Author
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Rumsby, P C, Campbell, P C, Niswander, L A, and Davidson, J N
- Abstract
When the multifunctional protein that catalyses the first three steps of pyrimidine biosynthesis in hamster cells is treated with staphylococcal V8 proteinase, a single cleavage takes place. The activities of carbamoyl-phosphate synthetase (EC 6.3.5.5), aspartate carbamoyltransferase (EC 2.1.3.2) and dihydro-orotase (EC 3.5.2.3) and the allosteric inhibition by UTP are unaffected. One fragment, of Mr 182000, has the first and third enzyme activities, whereas the other fragment, of Mr 42000, has aspartate carbamoyltransferase activity and an aggregation site. A similar small fragment is observed in protein digested with low concentrations of trypsin. A similar large fragment is seen after digestion with trypsin and as the predominating form of this protein in certain mutants defective in pyrimidine biosynthesis. These results indicate that a region located adjacent to the aspartate carbamoyltransferase domain is hypersensitive to proteinase action in vitro and may also be sensitive to proteolysis in vivo. more...
- Published
- 1984
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32. Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage.
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Zou, H, Wieser, R, Massagué, J, and Niswander, L
- Abstract
The bone morphogenetic proteins (BMPs), TGF beta superfamily members, play diverse roles in embryogenesis, but how the BMPs exert their action is unclear and how different BMP receptors (BMPRs) contribute to this process is not known. Here we demonstrate that the two type I BMPRs, BMPR-IA and BMPR-IB, regulate distinct processes during chick limb development. BmpR-IB expression in the embryonic limb prefigures the future cartilage primordium, and its activity is necessary for the initial steps of chondrogenesis. During later chondrogenesis, BmpR-IA is specifically expressed in prehypertrophic chondrocytes. BMPR-IA regulates chondrocyte differentiation, serving as a downstream mediator of Indian Hedgehog (IHH) function in both a local signaling loop and a longer-range relay system to PTHrP. BMPR-IB also regulates apoptosis: Expression of activated BMPR-IB results in increased cell death, and we showed previously that dominant-negative BMPR-IB inhibits apoptosis. Our studies indicate that in TGF beta signaling systems, different type I receptor isoforms are dedicated to specific functions during embryogenesis. more...
- Published
- 1997
33. Construction of a cDNA to the hamster CAD gene and its application toward defining the domain for aspartate transcarbamylase
- Author
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Shigesada, K, Stark, G R, Maley, J A, Niswander, L A, and Davidson, J N
- Abstract
cDNA complementary to hamster mRNA encoding the CAD protein, a multifunctional protein which carries the first three enzymes of pyrimidine biosynthesis, was constructed. The longest of these recombinants (pCAD142) covers 82% of the 7.9-kilobase mRNA. Portions of the cDNA were excised and replaced by a lac promoter-operator-initiation codon segment. The resultant plasmids were transfected into an Escherichia coli mutant defective in aspartate transcarbamylase, the second enzyme of the pathway. Complementation of the bacterial defect was observed with as little as 2.2 kilobases of cDNA sequence, corresponding to the 3' region of the mRNA. DNA sequencing in this region of the hamster cDNA reveals stretches which are highly homologous to the E. coli gene for the catalytic subunit of aspartate transcarbamylase; other stretches show no homology. The highly conserved regions probably reflect areas of protein structure critical to catalysis, while the nonconserved regions may reflect differences between the quaternary structures of E. coli and mammalian aspartate transcarbamylases, one such difference being that the bacterial enzyme in its native form is allosterically regulated and the mammalian enzyme is not. more...
- Published
- 1985
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34. Partial cDNA sequence to a hamster gene corrects defect in Escherichia coli pyrB mutant.
- Author
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Davidson, J N and Niswander, L A
- Abstract
The first three enzymes of pyrimidine biosynthesis (carbamoyl-phosphate synthetase, aspartate carbamoyl-transferase, and dihydro-orotase) are carried on a multifunctional protein in mammalian cells and are on separate proteins in bacteria. A plasmid containing a cDNA sequence corresponding to 80% of a hamster mRNA for this protein was transformed into Escherichia coli mutants lacking aspartate carbamoyltransferase (pyrB) or dihydro-orotase (pyrC). Only pyrB transformants were able to grow in the absence of uracil. Plasmid recovered from primary transformants was similar in size to the original plasmid and could yield prototrophs after secondary transformation of E. coli pyrB mutants. When cell extracts were prepared from pyrB transformants, high levels of aspartate carbamoyltransferase activity were found, and the enzyme had properties identical to the mammalian enzyme, including lack of allosteric regulation, precipitation by antiserum specific to the hamster multifunctional protein, and presence of a strong aggregation center. These results demonstrate that (i) a partial hamster protein can complement E. coli defective in pyrimidine biosynthesis, (ii) the order of the enzyme domains of the multifunctional protein is likely to be NH2-dihydro-orotase-carbamoyl-phosphate synthetase-aspartate carbamoyltransferase-COOH, and (iii) the enzyme domains appear to be self-contained at the DNA and protein levels. The protocol described here may be a general means for studying the domains of multifunctional proteins and for isolating other mammalian genes for which bacterial mutants have been prepared. It also permits study of the structure and function of the same gene in both prokaryotic and eukaryotic cells and may provide new insight into the evolution of complex genes. more...
- Published
- 1983
- Full Text
- View/download PDF
35. Contributors
- Author
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Akshoomoff, N., Bauer, P.J., Beltz, A.M., Berenbaum, S.A., Blakemore, J.E.O., Bowman, A.B., Bramen, J.E., Brooks-Kayal, A.R., Casey, B.J., Cohen, M.M., Colby, J.B., Colonnese, M., Cordeaux, C., Cubells, J.F., Davis, E.P., Decety, J., Ess, K.C., Feldman, D.E., Fernandez, L., Fitch, R.H., Fox, N.A., Franklin, N., Gillespie, D.C., Gunnar, M.R., Gweon, H., Hagerman, R.J., Haist, F., Hughes, C., Johnson, M.H., Johnson, S.P., Kano, M., Khazipov, R., Kim, S.-J., King, A.J., Kumar, K.K., Lahat, A., Lany, J., Leigh, M.J., Lein, P.J., Lepousez, G., Lewis, M., Lledo, P.-M., Michalska, K.J., Miller, M.W., Minlebaev, M., Molnár, Z., Mooney, S.M., Moreno-De-Luca, D., Muller, D., Nelson, C.A., III, Nikonenko, I., Niswander, L., O'Hare, E.D., Pelphrey, K., Persico, A.M., Polley, D.B., Posner, M.I., Pyrgaki, C., Reiter, L.T., Righi, G., Rothbart, M.K., Rubenstein, E., Rueda, M.R., Saffran, J.R., Sanchez, J.T., Saxe, R., Seery, A.M., Seidl, A.H., Sherr, E.H., Shulz, D.E., Sowell, E.R., Stanford, T.R., Stein, B.E., Stiles, J., Summar, K.L., Tager-Flusberg, H., Thomas, A.X., Tirrell, J., Urraca, N., Veenstra-VanderWeele, J., Voos, A., Wang, Y., and Watanabe, M. more...
- Published
- 2013
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- View/download PDF
36. BMP signaling and vertebrate limb development
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Zou H, Km, Choe, Lu Y, Joan Massague, and Niswander L
- Subjects
Embryonic Induction ,Bone Morphogenetic Proteins ,Vertebrates ,Animals ,Extremities ,Receptors, Cell Surface ,Receptors, Growth Factor ,Bone Morphogenetic Protein Receptors ,Chick Embryo ,Body Patterning ,Signal Transduction
37. The albino deletion complex and early postimplantation survival in the mouse
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Niswander, L., primary, Yee, D., additional, Rinchik, E.M., additional, Russell, L.B., additional, and Magnuson, T., additional
- Published
- 1988
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- View/download PDF
38. The albino-deletion complex in the mouse defines genes necessary for development of embryonic and extraembryonic ectoderm
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Niswander, L., primary, Yee, D., additional, Rinchik, E.M., additional, Russell, L.B., additional, and Magnuson, T., additional
- Published
- 1989
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- View/download PDF
39. FGF-4 replaces the apical ectodermal ridge and directs outgrowth and patterning of the limb
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Niswander, L
- Published
- 1993
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40. Limb mutants: what can they tell us about normal limb development?
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Niswander, L
- Published
- 1997
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- View/download PDF
41. RSG1 is required for cilia-dependent neural tube closure.
- Author
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Engelhardt D, Marean A, McKean D, Petersen J, and Niswander L
- Subjects
- Animals, Mice, Hedgehog Proteins metabolism, Hedgehog Proteins genetics, Neural Tube Defects genetics, Neural Tube Defects metabolism, Point Mutation, Signal Transduction, Cilia metabolism, Cilia genetics, Neural Tube embryology, Neural Tube metabolism
- Abstract
Cilia play a key role in the regulation of signaling pathways required for embryonic development, including the proper formation of the neural tube, the precursor to the brain and spinal cord. Forward genetic screens were used to generate mouse lines that display neural tube defects (NTD) and secondary phenotypes useful in interrogating function. We describe here the L3P mutant line that displays phenotypes of disrupted Sonic hedgehog signaling and affects the initiation of cilia formation. A point mutation was mapped in the L3P line to the gene Rsg1, which encodes a GTPase-like protein. The mutation lies within the GTP-binding pocket and disrupts the highly conserved G1 domain. The mutant protein and other centrosomal and IFT proteins still localize appropriately to the basal body of cilia, suggesting that RSG1 GTPase activity is not required for basal body maturation but is needed for a downstream step in axonemal elongation., (© 2024 Wiley Periodicals LLC.) more...
- Published
- 2024
- Full Text
- View/download PDF
42. Author Correction: MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses.
- Author
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Devine J, Vidal-García M, Liu W, Neves A, Lo Vercio LD, Green RM, Richbourg HA, Marchini M, Unger CM, Nickle AC, Radford B, Young NM, Gonzalez PN, Schuler RE, Bugacov A, Rolian C, Percival CJ, Williams T, Niswander L, Calof AL, Lander AD, Visel A, Jirik FR, Cheverud JM, Klein OD, Birnbaum RY, Merrill AE, Ackermann RR, Graf D, Hemberger M, Dean W, Forkert ND, Murray SA, Westerberg H, Marcucio RS, and Hallgrímsson B more...
- Published
- 2023
- Full Text
- View/download PDF
43. Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure.
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Engelhardt DM, Martyr CA, and Niswander L
- Subjects
- Epigenesis, Genetic, Folic Acid metabolism, Humans, Neurulation genetics, Neural Tube abnormalities, Neural Tube Defects genetics
- Abstract
Neural tube closure (NTC) is crucial for proper development of the brain and spinal cord and requires precise morphogenesis from a sheet of cells to an intact three-dimensional structure. NTC is dependent on successful regulation of hundreds of genes, a myriad of signaling pathways, concentration gradients, and is influenced by epigenetic and environmental cues. Failure of NTC is termed a neural tube defect (NTD) and is a leading class of congenital defects in the United States and worldwide. Though NTDs are all defined as incomplete closure of the neural tube, the pathogenesis of an NTD determines the type, severity, positioning, and accompanying phenotypes. In this review, we survey pathogenesis of NTDs relating to disruption of cellular processes arising from genetic mutations, altered epigenetic regulation, and environmental influences by micronutrients and maternal condition. This article is categorized under: Congenital Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Genetics/Genomics/Epigenetics Neurological Diseases > Stem Cells and Development., (© 2022 Wiley Periodicals LLC.) more...
- Published
- 2022
- Full Text
- View/download PDF
44. MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses.
- Author
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Devine J, Vidal-García M, Liu W, Neves A, Lo Vercio LD, Green RM, Richbourg HA, Marchini M, Unger CM, Nickle AC, Radford B, Young NM, Gonzalez PN, Schuler RE, Bugacov A, Rolian C, Percival CJ, Williams T, Niswander L, Calof AL, Lander AD, Visel A, Jirik FR, Cheverud JM, Klein OD, Birnbaum RY, Merrill AE, Ackermann RR, Graf D, Hemberger M, Dean W, Forkert ND, Murray SA, Westerberg H, Marcucio RS, and Hallgrímsson B more...
- Subjects
- Animals, Brain, X-Ray Microtomography, Databases, Factual, Mice anatomy & histology
- Abstract
Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N = 10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase ( www.facebase.org , https://doi.org/10.25550/3-HXMC ) and GitHub ( https://github.com/jaydevine/MusMorph )., (© 2022. The Author(s).) more...
- Published
- 2022
- Full Text
- View/download PDF
45. Micronutrient imbalance and common phenotypes in neural tube defects.
- Author
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Kakebeen AD and Niswander L
- Subjects
- Animals, Gene-Environment Interaction, Humans, Neural Tube Defects genetics, Micronutrients metabolism, Neural Tube Defects metabolism
- Abstract
Neural tube defects (NTDs) are among the most common birth defects, with a prevalence of close to 19 per 10,000 births worldwide. The etiology of NTDs is complex involving the interplay of genetic and environmental factors. Since nutrient deficiency is a risk factor and dietary changes are the major preventative measure to reduce the risk of NTDs, a more detailed understanding of how common micronutrient imbalances contribute to NTDs is crucial. While folic acid has been the most discussed environmental factor due to the success that population-wide fortification has had on prevention of NTDs, folic acid supplementation does not prevent all NTDs. The imbalance of several other micronutrients has been implicated as risks for NTDs by epidemiological studies and in vivo studies in animal models. In this review, we highlight recent literature deciphering the multifactorial mechanisms underlying NTDs with an emphasis on mouse and human data. Specifically, we focus on advances in our understanding of how too much or too little retinoic acid, zinc, and iron alter gene expression and cellular processes contributing to the pathobiology of NTDs. Synthesis of the discussed literature reveals common cellular phenotypes found in embryos with NTDs resulting from several micronutrient imbalances. The goal is to combine knowledge of these common cellular phenotypes with mechanisms underlying micronutrient imbalances to provide insights into possible new targets for preventative measures against NTDs., (© 2021 Wiley Periodicals LLC.) more...
- Published
- 2021
- Full Text
- View/download PDF
46. Loss of Grhl3 is correlated with altered cellular protrusions in the non-neural ectoderm during neural tube closure.
- Author
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Jaffe E and Niswander L
- Subjects
- Animals, Ectoderm ultrastructure, Female, Male, Mice, Inbred C57BL, Mice, Knockout, Mice, Cell Surface Extensions, DNA-Binding Proteins physiology, Ectoderm physiology, Neural Tube ultrastructure, Neurulation, Transcription Factors physiology
- Abstract
Background: The transcription factor Grainyhead-like 3 (GRHL3) has multiple roles in a variety of tissues during development including epithelial patterning and actin cytoskeletal regulation. During neural tube closure (NTC) in the mouse embryo, GRHL3 is expressed and functions in the non-neural ectoderm (NNE). Two important functions of GRHL3 are regulating the actin cytoskeleton during NTC and regulating the boundary between the NNE and neural ectoderm. However, an open question that remains is whether these functions explain the caudally restricted neural tube defect (NTD) of spina bifida observed in Grhl3 mutants., Results: Using scanning electron microscopy and immunofluorescence based imaging on Grhl3 mutants and wildtype controls, we show that GRHL3 is dispensable for NNE identity or epithelial maintenance in the caudal NNE but is needed for regulation of cellular protrusions during NTC. Grhl3 mutants have decreased lamellipodia relative to wildtype embryos during caudal NTC, first observed at the onset of delays when lamellipodia become prominent in wildtype embryos. At the axial level of NTD, half of the mutants show increased and disorganized filopodia and half lack cellular protrusions., Conclusion: These data suggest that altered cellular protrusions during NTC contribute to the etiology of NTD in Grhl3 mutants., (© 2020 American Association of Anatomists.) more...
- Published
- 2021
- Full Text
- View/download PDF
47. Association between rare variants in specific functional pathways and human neural tube defects multiple subphenotypes.
- Author
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Zou J, Wang F, Yang X, Wang H, Niswander L, Zhang T, and Li H
- Subjects
- Child, Child, Preschool, Cohort Studies, Female, Fetus, High-Throughput Nucleotide Sequencing, Humans, Infant, Infant, Newborn, Male, Neural Tube Defects metabolism, Neural Tube Defects physiopathology, Phenotype, Pregnancy, Sequence Analysis, DNA, Genetic Association Studies, Neural Tube Defects classification, Neural Tube Defects genetics
- Abstract
Background: Neural tube defects (NTDs) are failure of neural tube closure, which includes multiple central nervous system phenotypes. More than 300 mouse mutant strains exhibits NTDs phenotypes and give us some clues to establish association between biological functions and subphenotypes. However, the knowledge about association in human remains still very poor., Methods: High throughput targeted genome DNA sequencing were performed on 280 neural tube closure-related genes in 355 NTDs cases and 225 ethnicity matched controls, RESULTS: We explored that potential damaging rare variants in genes functioning in chromatin modification, apoptosis, retinoid metabolism and lipid metabolism are associated with human NTDs. Importantly, our data indicate that except for planar cell polarity pathway, craniorachischisis is also genetically related with chromatin modification and retinoid metabolism. Furthermore, single phenotype in cranial or spinal regions displays significant association with specific biological function, such as anencephaly is associated with potentially damaging rare variants in genes functioning in chromatin modification, encephalocele is associated with apoptosis, retinoid metabolism and one carbon metabolism, spina bifida aperta and spina bifida cystica are associated with apoptosis; lumbar sacral spina bifida aperta and spina bifida occulta are associated with lipid metabolism. By contrast, complex phenotypes in both cranial and spinal regions display association with various biological functions given the different phenotypes., Conclusions: Our study links genetic variant to subphenotypes of human NTDs and provides a preliminary but direct clue to investigate pathogenic mechanism for human NTDs. more...
- Published
- 2020
- Full Text
- View/download PDF
48. Low folate concentration impacts mismatch repair deficiency in neural tube defects.
- Author
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Li H, Wang X, Zhao H, Wang F, Bao Y, Guo J, Chang S, Wu L, Cheng H, Chen S, Zou J, Cui X, Niswander L, Finnell RH, Wang H, and Zhang T
- Subjects
- Folic Acid metabolism, Folic Acid Deficiency metabolism, Genetic Variation, Histones metabolism, Humans, DNA Mismatch Repair genetics, Disease Susceptibility, Folic Acid Deficiency complications, Neural Tube Defects etiology, Neural Tube Defects metabolism
- Abstract
Aim: To know the cause of sequence variants in neural tube defect (NTD). Materials & methods: We sequenced genes implicated in neural tube closure (NTC) in a Chinese cohort and elucidated the molecular mechanism-driving mutations. Results: In NTD cases, an increase in specific variants was identified, potentially deleterious rare variants harbored in H3K36me3 occupancy regions that recruits mismatch repair (MMR) machinery. Lower folate concentrations in local brain tissues were also observed. In neuroectoderm cells, folic acid insufficiency attenuated association of Msh6 to H3K36me3, and reduced bindings to NTC genes. Rare variants in human NTDs were featured by MMR deficiency and more severe microsatellite instability. Conclusion: Our work suggests a mechanistic link between folate insufficiency and MMR deficiency that correlates with an increase of rare variants in NTC genes. more...
- Published
- 2020
- Full Text
- View/download PDF
49. An Injectable Reverse Thermal Gel for Minimally Invasive Coverage of Mouse Myelomeningocele.
- Author
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Bardill J, Williams SM, Shabeka U, Niswander L, Park D, and Marwan AI
- Subjects
- Acrylic Resins, Animals, Female, Male, Materials Testing, Mice, Minimally Invasive Surgical Procedures, Pregnancy, Biocompatible Materials therapeutic use, Fetoscopy, Meningomyelocele surgery
- Abstract
Background: Myelomeningocele (MMC) results in lifelong neurologic and functional deficits. Currently, prenatal repair of MMC closes the defect, resulting in a 50% reduction in postnatal ventriculoperitoneal shunting. However, this invasive fetal surgery is associated with significant morbidities to mother and baby. We have pioneered a novel reverse thermal gel (RTG) to cover MMC defects in a minimally invasive manner. Here, we test in-vitro RTG long-term stability in amniotic fluid and in vivo application in the Grainy head-like 3 (Grhl3) mouse MMC model., Materials and Methods: RTG stability in amniotic fluid (in-vitro) was monitored for 6 mo and measured using gel permeation chromatography and solution-gel transition temperature (lower critical solution temperature). E16.5 Grhl3 mouse fetuses were injected with the RTG or saline and harvested on E19.5. Tissue was assessed for RTG coverage of the gross defect and inflammatory response by immunohistochemistry for macrophages., Results: Polymer backbone molecular weight and lower critical solution temperature remain stable in amniotic fluid after 6 mo. Needle injection over the MMC of Grhl3 fetuses successfully forms a stable gel that covers the entire defect. On harvest, some animals demonstrate >50% RTG coverage. RTG injection is not associated with inflammation., Conclusions: Our results demonstrate that the RTG is a promising candidate for a minimally invasive approach to patch MMC. We are now poised to test our RTG patch in the large preclinical ovine model used to evaluate prenatal repair of MMC., (Copyright © 2018 Elsevier Inc. All rights reserved.) more...
- Published
- 2019
- Full Text
- View/download PDF
50. Intratumoral heterogeneity of endogenous tumor cell invasive behavior in human glioblastoma.
- Author
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Parker JJ, Canoll P, Niswander L, Kleinschmidt-DeMasters BK, Foshay K, and Waziri A
- Subjects
- Cell Movement drug effects, Cell Proliferation drug effects, Drug Screening Assays, Antitumor, Gefitinib pharmacology, Humans, Neoplasm Invasiveness, Primary Cell Culture, Tissue Culture Techniques, Tumor Cells, Cultured, Brain Neoplasms pathology, Glioblastoma pathology
- Abstract
Intratumoral genetic heterogeneity is a widely accepted characteristic of human cancer, including the most common primary malignant brain tumor, glioblastoma. However, the variability in biological behaviors amongst cells within individual tumors is not well described. Invasion into unaffected brain parenchyma is one such behavior, and a leading mechanism of tumor recurrence unaddressed by the current therapeutic armamentarium. Further, providing insight into variability of tumor cell migration within individual tumors may inform discovery of novel anti-invasive therapeutics. In this study, ex vivo organotypic slice cultures from EGFR-wild type and EGFR-amplified patient tumors were treated with the EGFR inhibitor gefitinib to evaluate potential sub-population restricted intratumoral drug-specific responses. High-resolution time-lapse microscopy and quantitative path tracking demonstrated migration of individual cells are punctuated by intermittent bursts of movement. Elevation of population aggregate mean speeds were driven by subpopulations of cells exhibiting frequent high-amplitude bursts, enriched within EGFR-amplified tumors. Treatment with gefitinib specifically targeted high-burst cell subpopulations only in EGFR-amplified tumors, decreasing bursting frequency and amplitude. We provide evidence of intratumoral subpopulations of cells with enhanced migratory behavior in human glioblastoma, selectively targeted via EGFR inhibition. These data justify use of direct human tumor slice cultures to investigate patient-specific therapies designed to limit tumor invasion. more...
- Published
- 2018
- Full Text
- View/download PDF
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