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372 results on '"Louvi A"'

1. Dysregulation of mTOR signalling is a converging mechanism in lissencephaly

Author

Zhang, Ce, Liang, Dan, Ercan-Sencicek, A. Gulhan, Bulut, Aybike S., Cortes, Joelly, Cheng, Iris Q., Henegariu, Octavian, Nishimura, Sayoko, Wang, Xinyuan, Peksen, A. Buket, Takeo, Yutaka, Caglar, Caner, Lam, TuKiet T., Koroglu, Merve Nur, Narayanan, Anand, Lopez-Giraldez, Francesc, Miyagishima, Danielle F., Mishra-Gorur, Ketu, Barak, Tanyeri, Yasuno, Katsuhito, Erson-Omay, E. Zeynep, Yalcinkaya, Cengiz, Wang, Guilin, Mane, Shrikant, Kaymakcalan, Hande, Guzel, Aslan, Caglayan, A. Okay, Tuysuz, Beyhan, Sestan, Nenad, Gunel, Murat, Louvi, Angeliki, and Bilguvar, Kaya

Published
2025
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2. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas

Author

Mark W. Youngblood, Zeynep Erson-Omay, Chang Li, Hinda Najem, Süleyman Coșkun, Evgeniya Tyrtova, Julio D. Montejo, Danielle F. Miyagishima, Tanyeri Barak, Sayoko Nishimura, Akdes Serin Harmancı, Victoria E. Clark, Daniel Duran, Anita Huttner, Timuçin Avşar, Yasar Bayri, Johannes Schramm, Julien Boetto, Matthieu Peyre, Maximilien Riche, Roland Goldbrunner, Nduka Amankulor, Angeliki Louvi, Kaya Bilgüvar, M. Necmettin Pamir, Koray Özduman, Türker Kilic, James R. Knight, Matthias Simon, Craig Horbinski, Michel Kalamarides, Marco Timmer, Amy B. Heimberger, Ketu Mishra-Gorur, Jennifer Moliterno, Katsuhito Yasuno, and Murat Günel

Subjects
Science
Abstract

Abstract Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway in neoplasia.

Published
2023
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3. Microcephaly-associated protein WDR62 shuttles from the Golgi apparatus to the spindle poles in human neural progenitors

Author

Claudia Dell'Amico, Marilyn M Angulo Salavarria, Yutaka Takeo, Ichiko Saotome, Maria Teresa Dell'Anno, Maura Galimberti, Enrica Pellegrino, Elena Cattaneo, Angeliki Louvi, and Marco Onorati

Subjects
microcephaly, MCPH, WDR62, neurodevelopmental disorders, iPSCs, disease modeling, Medicine, Science, Biology (General), QH301-705.5
Abstract

WDR62 is a spindle pole-associated scaffold protein with pleiotropic functions. Recessive mutations in WDR62 cause structural brain abnormalities and account for the second most common cause of autosomal recessive primary microcephaly (MCPH), indicating WDR62 as a critical hub for human brain development. Here, we investigated WDR62 function in corticogenesis through the analysis of a C-terminal truncating mutation (D955AfsX112). Using induced Pluripotent Stem Cells (iPSCs) obtained from a patient and his unaffected parent, as well as isogenic corrected lines, we generated 2D and 3D models of human neurodevelopment, including neuroepithelial stem cells, cerebro-cortical progenitors, terminally differentiated neurons, and cerebral organoids. We report that WDR62 localizes to the Golgi apparatus during interphase in cultured cells and human fetal brain tissue, and translocates to the mitotic spindle poles in a microtubule-dependent manner. Moreover, we demonstrate that WDR62 dysfunction impairs mitotic progression and results in alterations of the neurogenic trajectories of iPSC neuroderivatives. In summary, impairment of WDR62 localization and function results in severe neurodevelopmental abnormalities, thus delineating new mechanisms in the etiology of MCPH.

Published
2023
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4. Interferon-γ resistance and immune evasion in glioma develop via Notch-regulated co-evolution of malignant and immune cells

Author

Parmigiani, Elena, Ivanek, Robert, Rolando, Chiara, Hafen, Katrin, Turchinovich, Gleb, Lehmann, Frank Michael, Gerber, Alexandra, Brkic, Sime, Frank, Stephan, Meyer, Sara C., Wakimoto, Hiroaki, Günel, Murat, Louvi, Angeliki, Mariani, Luigi, Finke, Daniela, Holländer, Georg, Hutter, Gregor, Tussiwand, Roxane, Taylor, Verdon, and Giachino, Claudio

Published
2022
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6. PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans

Author

Barak, Tanyeri, Ristori, Emma, Ercan-Sencicek, A. Gulhan, Miyagishima, Danielle F., Nelson-Williams, Carol, Dong, Weilai, Jin, Sheng Chih, Prendergast, Andrew, Armero, William, Henegariu, Octavian, Erson-Omay, E. Zeynep, Harmancı, Akdes Serin, Guy, Mikhael, Gültekin, Batur, Kilic, Deniz, Rai, Devendra K., Goc, Nükte, Aguilera, Stephanie Marie, Gülez, Burcu, Altinok, Selin, Ozcan, Kent, Yarman, Yanki, Coskun, Süleyman, Sempou, Emily, Deniz, Engin, Hintzen, Jared, Cox, Andrew, Fomchenko, Elena, Jung, Su Woong, Ozturk, Ali Kemal, Louvi, Angeliki, Bilgüvar, Kaya, Connolly, Jr., E. Sander, Khokha, Mustafa K., Kahle, Kristopher T., Yasuno, Katsuhito, Lifton, Richard P., Mishra-Gorur, Ketu, Nicoli, Stefania, and Günel, Murat

Published
2021
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23. Performance of modified and low complexity pulse shaping filters for IEEE 802.11 OFDM transmission

Author

Tulsi Pawan Fowdur and Louvi Doorganah

Subjects
OFDM, pulse shaping filters, complexity, ISI, fading, Telecommunication, TK5101-6720, Information technology, T58.5-58.64
Abstract

The most commonly used multicarrier modulation method in 802.11 wireless communication systems is Orthogonal Frequency Division Multiplexing (OFDM). However, OFDM is easily affected by Inter Symbol Interference (ISI). In this paper, different pulse shaping filters are employed in the OFDM system and three new filters are presented to further reduce ISI effects. The first one is a Modified Parametric Exponential Pulse (MPEXP) filter which employs a different transfer function that is implemented at the transmitter side. The second one is a Better Than Modified Flipped Exponential Pulse (BTMFEXP) filter which is derived by modifying the transfer function of Modified Flipped Exponential Pulse (MFEXP). The third one is a hybrid of BTMFEXP and MPEXP (HBTMFPEXP). Lastly, low complexity forms of the MFEXP and BTMFEXP, derived from Taylor Series, are implemented. The OFDM system was tested with the existing and proposed pulses over AWGN and Fading channels. The proposed filters show better Bit Error Rate (BER) performance. Under a high ISI level, BTMFEXP and HBTMFPEXP showed a gain of 0.23 and 0.57 dB respectively over MFEXP with AWGN channel. With a fading channel at high ISI level, the proposed BTMFEXP and HBTMFPEXP demonstrated a gain of 2.33 and 5.33 dB respectively over MFEXP.

Published
2019
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26. Sequence Variants in SLITRK1 Are Associated with Tourette's Syndrome

Author

Abelson, Jesse F., Kwan, Kenneth Y., O'Roak, Brian J., Baek, Danielle Y., Stillman, Althea A., Morgan, Thomas M., Mathews, Carol A., Pauls, David L., Rašin, Mladen-Roko, Gunel, Murat, Davis, Nicole R., Ercan-Sencicek, A. Gulhan, Guez, Danielle H., Spertus, John A., Leckman, James F., Dure, Leon S., Kurlan, Roger, Singer, Harvey S., Gilbert, Donald L., Farhi, Anita, Louvi, Angeliki, Lifton, Richard P., Šestan, Nenad, and State, Matthew W.

Published
2005

27. Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations.

Author

Bilgüvar, Kaya, Oztürk, Ali Kemal, Louvi, Angeliki, Kwan, Kenneth Y, Choi, Murim, Tatli, Burak, Yalnizoğlu, Dilek, Tüysüz, Beyhan, Cağlayan, Ahmet Okay, Gökben, Sarenur, Kaymakçalan, Hande, Barak, Tanyeri, Bakircioğlu, Mehmet, Yasuno, Katsuhito, Ho, Winson, Sanders, Stephan, Zhu, Ying, Yilmaz, Sanem, Dinçer, Alp, Johnson, Michele H, Bronen, Richard A, Koçer, Naci, Per, Hüseyin, Mane, Shrikant, Pamir, Mehmet Necmettin, Yalçinkaya, Cengiz, Kumandaş, Sefer, Topçu, Meral, Ozmen, Meral, Sestan, Nenad, Lifton, Richard P, State, Matthew W, and Günel, Murat

Subjects
Brain, Animals, Humans, Mice, Microcephaly, Brain Diseases, Nerve Tissue Proteins, Pedigree, DNA Mutational Analysis, Base Sequence, Genes, Recessive, Mutation, Molecular Sequence Data, Female, Male, Genes, Recessive, General Science & Technology
Abstract

The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.

Published
2010

29. Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas

Author

Youngblood, Mark W., primary, Erson-Omay, Zeynep, additional, Li, Chang, additional, Najem, Hinda, additional, Coșkun, Süleyman, additional, Tyrtova, Evgeniya, additional, Montejo, Julio D., additional, Miyagishima, Danielle F., additional, Barak, Tanyeri, additional, Nishimura, Sayoko, additional, Harmancı, Akdes Serin, additional, Clark, Victoria E., additional, Duran, Daniel, additional, Huttner, Anita, additional, Avşar, Timuçin, additional, Bayri, Yasar, additional, Schramm, Johannes, additional, Boetto, Julien, additional, Peyre, Matthieu, additional, Riche, Maximilien, additional, Goldbrunner, Roland, additional, Amankulor, Nduka, additional, Louvi, Angeliki, additional, Bilgüvar, Kaya, additional, Pamir, M. Necmettin, additional, Özduman, Koray, additional, Kilic, Türker, additional, Knight, James R., additional, Simon, Matthias, additional, Horbinski, Craig, additional, Kalamarides, Michel, additional, Timmer, Marco, additional, Heimberger, Amy B., additional, Mishra-Gorur, Ketu, additional, Moliterno, Jennifer, additional, Yasuno, Katsuhito, additional, and Günel, Murat, additional

Published
2023
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33. Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease

Author

Mishra-Gorur, Ketu, primary, Barak, Tanyeri, additional, Kaulen, Leon D., additional, Henegariu, Octavian, additional, Jin, Sheng Chih, additional, Aguilera, Stephanie Marie, additional, Yalbir, Ezgi, additional, Goles, Gizem, additional, Nishimura, Sayoko, additional, Miyagishima, Danielle, additional, Djenoune, Lydia, additional, Altinok, Selin, additional, Rai, Devendra K., additional, Viviano, Stephen, additional, Prendergast, Andrew, additional, Zerillo, Cynthia, additional, Ozcan, Kent, additional, Baran, Burcin, additional, Sencar, Leman, additional, Goc, Nukte, additional, Yarman, Yanki, additional, Ercan-Sencicek, A. Gulhan, additional, Bilguvar, Kaya, additional, Lifton, Richard P., additional, Moliterno, Jennifer, additional, Louvi, Angeliki, additional, Yuan, Shiaulou, additional, Deniz, Engin, additional, Brueckner, Martina, additional, and Gunel, Murat, additional

Published
2023
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34. Author response: Microcephaly-associated protein WDR62 shuttles from the Golgi apparatus to the spindle poles in human neural progenitors

Author

Dell'Amico, Claudia, primary, Angulo Salavarria, Marilyn M, additional, Takeo, Yutaka, additional, Saotome, Ichiko, additional, Dell'Anno, Maria Teresa, additional, Galimberti, Maura, additional, Pellegrino, Enrica, additional, Cattaneo, Elena, additional, Louvi, Angeliki, additional, and Onorati, Marco, additional

Published
2023
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35. Pleiotropic role of TRAF7 in skull-base meningiomas and congenital heart disease

Author

Ketu Mishra-Gorur, Tanyeri Barak, Leon D. Kaulen, Octavian Henegariu, Sheng Chih Jin, Stephanie Marie Aguilera, Ezgi Yalbir, Gizem Goles, Sayoko Nishimura, Danielle Miyagishima, Lydia Djenoune, Selin Altinok, Devendra K. Rai, Stephen Viviano, Andrew Prendergast, Cynthia Zerillo, Kent Ozcan, Burcin Baran, Leman Sencar, Nukte Goc, Yanki Yarman, A. Gulhan Ercan-Sencicek, Kaya Bilguvar, Richard P. Lifton, Jennifer Moliterno, Angeliki Louvi, Shiaulou Yuan, Engin Deniz, Martina Brueckner, and Murat Gunel

Subjects
Multidisciplinary
Abstract

While somatic variants of TRAF7 (Tumor necrosis factor receptor-associated factor 7) underlie anterior skull-base meningiomas, here we report the inherited mutations of TRAF7 that cause congenital heart defects. We show that TRAF7 mutants operate in a dominant manner, inhibiting protein function via heterodimerization with wild-type protein. Further, the shared genetics of the two disparate pathologies can be traced to the common origin of forebrain meninges and cardiac outflow tract from the TRAF7- expressing neural crest. Somatic and inherited mutations disrupt TRAF7–IFT57 interactions leading to cilia degradation. TRAF7 -mutant meningioma primary cultures lack cilia, and TRAF7 knockdown causes cardiac, craniofacial, and ciliary defects in Xenopus and zebrafish, suggesting a mechanistic convergence for TRAF7 -driven meningiomas and developmental heart defects.

Published
2023
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36. Architecture et pouvoir

Author

Louvi-Kizi, Aspasia

Subjects
Christliche Kunst, art byzantin, crusade, arte cristiano, arte cristiana, HBLC, crociata, Impero bizantino, Byzantinische Kunst, croisade, Architecture, Byzantine art, HIS037010, art chrétien, arte bizantina, art gothique, Cantacuzene, Lusignan, Gothic art, ACK, Cantacuzène, Arts & Humanities, Cultural studies, cruzada, Byzantinische Reich, Byzantine Empire, arte bizantino, arte gótico, Imperio bizantino, Kunst der Gotik, Christian art, Empire byzantin, ART015070, Art
Abstract

L’œuvre de bâtisseurs de Manuel Cantacuzène et d’Isabelle de Lusignan Pendant ses trente ans de despotat à Mistra, Manuel Cantacuzène accomplit une œuvre considérable de bâtisseur : en fait, il donna forme à la cité de Mistra. Et sa femme Isabelle joua un grand rôle dans cette entreprise. Son arrivée à Mistra en 1355, date à laquelle elle épousa Manuel Cantacuzène, et les données archéologiques permettent d’établir la chronologie de leur œuvre de bâtisseurs. Quand Isabelle revendiquait l’héri...

Published
2023

37. La vie d’Isabelle de Lusignan, dite aussi Ζαµπεας ντε Λεζηναω ou Marie-Marguerite

Author

Louvi-Kizi, Aspasia

Subjects
Christliche Kunst, art byzantin, crusade, arte cristiano, arte cristiana, HBLC, crociata, Impero bizantino, Byzantinische Kunst, croisade, Architecture, Byzantine art, HIS037010, art chrétien, arte bizantina, art gothique, Cantacuzene, Lusignan, Gothic art, ACK, Cantacuzène, Arts & Humanities, Cultural studies, cruzada, Byzantinische Reich, Byzantine Empire, arte bizantino, arte gótico, Imperio bizantino, Kunst der Gotik, Christian art, Empire byzantin, ART015070, Art
Abstract

Isabelle naît à Constantinople en 1333 ou 1334 du second mariage de Guy de Lusignan avec la fille du dignitaire byzantin Syrgiannis. Des lettres papales nous apprennent que la mère d’Isabelle, Théodora Syrgianni, était apparentée à la première épouse de Guy, née Cantacuzène, ainsi qu’à la famille des Paléologues. Le père d’Isabelle, Guy de Lusignan (1290-1344), également connu sous le nom de Syrgis dans les sources byzantines, était le fils d’une autre Isabelle, elle-même fille du roi de Peti...

Published
2023

38. Introduction

Author

Louvi-Kizi, Aspasia

Subjects
Christliche Kunst, art byzantin, crusade, arte cristiano, arte cristiana, HBLC, crociata, Impero bizantino, Byzantinische Kunst, croisade, Architecture, Byzantine art, HIS037010, art chrétien, arte bizantina, art gothique, Cantacuzene, Lusignan, Gothic art, ACK, Cantacuzène, Arts & Humanities, Cultural studies, cruzada, Byzantinische Reich, Byzantine Empire, arte bizantino, arte gótico, Imperio bizantino, Kunst der Gotik, Christian art, Empire byzantin, ART015070, Art
Abstract

Au regard des recherches potentielles qu’offre la cité forteresse de Mistra, le nombre d’études publiées jusqu’à présent est décevant. Elle attend encore des archéologues byzantinistes chevronnés qui mèneront des fouilles systématiques et approfondiront l’étude de chaque monument. En 1910, Gabriel Millet publiait son précieux Album, révélant l’image d’une cité en ruines à la fin du xixe siècle, après avoir vécu deux épisodes dévastateurs pendant la domination ottomane (fig. 1 ; 3a). Millet se...

Published
2023

39. Le monastère de la Pantanassa

Author

Louvi-Kizi, Aspasia

Subjects
Christliche Kunst, art byzantin, crusade, arte cristiano, arte cristiana, HBLC, crociata, Impero bizantino, Byzantinische Kunst, croisade, Architecture, Byzantine art, HIS037010, art chrétien, arte bizantina, art gothique, Cantacuzene, Lusignan, Gothic art, ACK, Cantacuzène, Arts & Humanities, Cultural studies, cruzada, Byzantinische Reich, Byzantine Empire, arte bizantino, arte gótico, Imperio bizantino, Kunst der Gotik, Christian art, Empire byzantin, ART015070, Art
Abstract

Selon la tradition, comme nous l’avons signalé, le monastère de la Pantanassa était en même temps dédié au Christ Zoodotis. Néanmoins, Manolis Chatzidakis a soutenu que le monastère Zoodotou devait être identifié à Agia Sophia, et ce, parce qu’il n’avait pas distingué de « trace d’aménagement ou de rénovation » dans la Pantanassa. Plus précisément, il dit : « L’identification de la Pantanassa avec le “monastère du Zoodotis”, dont nous savons par des textes et des sigilles (sceaux) qu’il fut f...

Published
2023

40. Altered Expression of Several Molecular Mediators of Cerebrospinal Fluid Production inHypMice

Author

Jared Kaplan, Steven Tommasini, Gang-Qing Yao, Meiling Zhu, Sayoko Nishimura, Sevanne Ghazarian, Angeliki Louvi, and Karl Insogna

Subjects
Endocrinology, Diabetes and Metabolism
Abstract

ContextX-linked hypophosphatemia (XLH) is a genetic disease, causing life-long hypophosphatemia due to overproduction of fibroblast growth factor 23 (FGF23). XLH is associated with Chiari malformations, cranial synostosis, and syringomyelia. FGF23 signals through FGFR1c and requires a coreceptor, α-Klotho, which is expressed in the renal distal convoluted tubules and the choroid plexus (ChP). In the ChP, α-Klotho participates in regulating cerebrospinal fluid (CSF) production by shuttling the sodium/potassium adenosine triphosphatase (Na+/K+-ATPase) to the luminal membrane. The sodium/potassium/chloride cotransporter 1 (NKCC1) also makes a substantial contribution to CSF production.ObjectiveSince CSF production has not been studied in XLH, we sought to determine if there are changes in the expression of these molecules in the ChP of Hyp mice, the murine model of XLH, as a first step toward testing the hypothesis that altered CSF production contributes to the cranial and spinal malformations seen this disease.MethodsSemi-quantitative real-time PCR was used to analyze the level of expression of transcripts for Fgfr1c, and thee key regulators of CSF production, Klotho, Atp1a1 and Slc12a2. In situ hybridization was used to provide anatomical localization for the encoded proteins.ResultsReal-time polymerase chain reaction (RT-PCR) demonstrated significant upregulation of Klotho transcripts in the fourth ventricle of Hyp mice compared to controls. Transcript levels for Fgfr1c were unchanged in Hyp mice. Atp1a1 transcripts encoding the alpha-1 subunit of Na+/K+-ATPase were significantly downregulated in the third and lateral ventricles (LV). Expression levels of the Slc12a2 transcript (which encodes NKCC1) were unchanged in Hyp mice compared to controls. In situ hybridization (ISH) confirmed the presence of all 4 transcripts in the LV ChP both of WT and Hyp mice.ConclusionThis is the first study to document a significant change in the level of expression of the molecular machinery required for CSF production in Hyp mice. Whether similar changes occur in patients with XLH, potentially contributing to the cranial and spinal cord abnormalities frequently seen in XLH, remains to be determined.

Published
2023
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42. Mutations in KATNB1 Cause Complex Cerebral Malformations by Disrupting Asymmetrically Dividing Neural Progenitors

Author

Mishra-Gorur, Ketu, Çağlayan, Ahmet Okay, Schaffer, Ashleigh E., Chabu, Chiswili, Henegariu, Octavian, Vonhoff, Fernando, Akgümüş, Gözde Tuğce, Nishimura, Sayoko, Han, Wenqi, Tu, Shu, Baran, Burçin, Gümüş, Hakan, Dilber, Cengiz, Zaki, Maha S., Hossni, Heba A.A., Rivière, Jean-Baptiste, Kayserili, Hülya, Spencer, Emily G., Rosti, Rasim Ö., Schroth, Jana, Per, Hüseyin, Çağlar, Caner, Çağlar, Çağri, Dölen, Duygu, Baranoski, Jacob F., Kumandaş, Sefer, Minja, Frank J., Erson-Omay, E. Zeynep, Mane, Shrikant M., Lifton, Richard P., Xu, Tian, Keshishian, Haig, Dobyns, William B., Chi, Neil C., Šestan, Nenad, Louvi, Angeliki, Bilgüvar, Kaya, Yasuno, Katsuhito, Gleeson, Joseph G., and Günel, Murat

Published
2014
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45. Microcephaly-associated WDR62 mutations hamper Golgi apparatus-to-spindle pole shuttling in human neural progenitors

Author

Claudia Dell’Amico, Marilyn M. Angulo Salavarria, Yutaka Takeo, Ichiko Saotome, Maria Teresa Dell’Anno, Maura Galimberti, Enrica Pellegrino, Elena Cattaneo, Angeliki Louvi, and Marco Onorati

Abstract

WDR62 is a spindle pole-associated scaffold protein with pleiotropic functions during corticogenesis. Recessive mutations in WDR62 are associated with structural brain abnormalities and account for the second most common cause of autosomal recessive primary microcephaly (MCPH), indicating WDR62 as a critical hub for human brain development. Here, we investigated a C-terminal truncating mutation (D955AfsX112) in WDR62 using induced pluripotent stem cells (iPSCs) obtained from a patient with MCPH2. We generated neuroepithelial stem (NES) cells and cerebro-cortical progenitors and neurons from patient-derived and isogenic retro-mutated iPSC lines. We found that WDR62 dysfunction resulted in impaired cell cycle progression and alterations of the neurogenic trajectories of iPSC neuroderivatives. Moreover, we report WDR62 localization at the Golgi apparatus during interphase, both in human neural progenitors in vitro and in human fetal brain tissue. WDR62 shuttling from the Golgi apparatus to spindle poles is dynamic and microtubule-dependent. Impairment of WDR62 function and localization results in severe neurodevelopmental abnormalities, thus delineating new mechanisms in MCPH etiology.

Published
2022
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46. Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration

Author

Bilguvar, Kaya, Tyagi, Navneet K., Ozkara, Cigdem, Tuysuz, Beyhan, Bakircioglu, Mehmet, Choi, Murim, Delil, Sakir, Caglayan, Ahmet O., Baranoski, Jacob F., Erturk, Ozdem, Yalcinkaya, Cengiz, Karacorlu, Murat, Dincer, Alp, Johnson, Michele H., Mane, Shrikant, Chandra, Sreeganga S., Louvi, Angeliki, Boggon, Titus J., Lifton, Richard P., Horwich, Arthur L., and Gunel, Murat

Published
2013

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