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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2005.07.021 Byline: Junfeng Wang (a), Gamze Kilic (a), Muge Aydin (b), Zoe Burke (c), Guillermo Oliver (a), Beatriz Sosa-Pineda (a) Keywords: Pancreas; Prox1; Mouse; Endocrine; Exocrine; Development; Ontogeny; Embryo; Cholecystokinin Abstract: The development of the mammalian pancreas is governed by various signaling processes and by a cascade of gene activation events controlled by different transcription factors. Here we show that the divergent homeodomain transcription factor Prox1 is a novel, crucial regulator of mouse pancreas organogenesis. Loss of Prox1 function severely disrupted epithelial pancreas morphology and hindered pancreatic growth without affecting significantly the genesis of endocrine cells before E11.5. Conversely, the lack of Prox1 activity substantially decreased the formation of islet cell precursors after E13.5, during a period known as the 'secondary transition'. Notably, this defect occurred concurrently with an abnormal increment of exocrine cells. Hence, it is possible that Prox1 contributes to the allocation of an adequate supply of islet cells throughout pancreas ontogeny by preventing exocrine cell differentiation of multipotent pancreatic progenitors. Prox1 thus appears to be an essential component of a genetic program destined to produce the cellular complexity of the mammalian pancreas. Author Affiliation: (a) Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA (b) Department of Genetics, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey (c) Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath BA27AY, UK Article History: Received 22 March 2005; Revised 15 July 2005; Accepted 18 July 2005

The anterior segment of the vertebrate eye consists of highly organized and specialized ocular tissues critical for normal vision. The periocular mesenchyme, originating from the neural crest, contributes extensively to the anterior segment. During chick eye morphogenesis, the homeobox gene Six3 is expressed in a subset of periocular mesenchymal cells and in differentiating anterior segment tissues. Retrovirus-mediated misexpression of Six3 causes eye anterior segment malformation, including corneal protrusion and opacification, ciliary body and iris hypoplasia, and trabecular meshwork dysgenesis. Histological and molecular marker analyses demonstrate that Six3 misexpression disrupts the integrity of the corneal endothelium and the expression of extracellular matrix components critical for corneal transparency. Six3 misexpression also leads to a reduction of the periocular mesenchymal cell population expressing Lmx1b, Pitx2, and Pax6, transcription factors critical for eye anterior segment morphogenesis. Moreover, elevated levels of Six3 attenuate proliferation of periocular mesenchymal cells in vitro and differentiating anterior segment tissues in vivo. These results suggest that, in addition to its function in eye primordium determination, Six3 plays a role in regulating the development of the vertebrate eye anterior segment. Keywords: eye; development; anterior segment; mesenchyme; Six3; misexpression; chick.

Old and new insights into the development and biological function of the lymphatic vasculature are discussed in this review article. The recent discovery of molecules that specifically control lymphatic development and lymphatic vessel growth and the identification of new lymphatic endothelium-specific markers have helped bring key scientific advances and given insights into the molecular mechanisms that control lymphatic development and function. Topics include developmental lymphangiogenesis and lymphatic markers, clinical implications, lymphatic regeneration, lymphedema, and tumor lymphangiogenesis.

Results demonstrate that synergistic regulation of vertebrate muscle development involves Drosophila gene dachshund2, vertebrate homologs Eya2 and Six1 and physical interaction between the respective gene encoded proteins. This study illustrates a new regulatory pathway for myogenic specification in the embryonic precursors of the skeletal muscle development.

Function of Prox1 (ital), a homeobox gene which is necessary for development of the murine lymphatic system, is discussed. The gene is expressed in a subpopulation of endothelial cells that give rise through budding and sprouting to the lymphatic system. The budding and sprouting is arrested in Prox1 (ital) null mice, but angiogenesis and vasculogenesis of the vascular system are not affected.

Proteinases from Lactobacillus plantarum release lysine, arginine, and leucine when hydrolyzing myofibrillar proteins but release alanine when hydrolyzing sarcoplasmic proteins. This bacterium is used to cure sausages, and manipulating the starter culture can affect the taste and aroma of the finished product.

Research was conducted to examine the hydrolysis of pork muscle sarcoplasmic proteins by Lactobacillus curvatus and Lactobacillus sake. The objective is to determine the proteolytic activities of various enzyme combinations from L. curvatus and L. sake strains on sarcoplasmic proteins to predict their suitability and their proteolytic enzymes as starter cultures or additives, respectively, for the processing of dry fermented sausages. Results suggest that the differences in proteolytic activities may result in distinct flavor profiles for final products.

Several genes involved in the regulation of eye development in different species have been identified. Structural and functional conservation have been found between some of these genes in organisms as diverse as Drosophila and mouse. One notable example is the relationship between the mouse Pax6 gene and eyeless of Drosophila. Ectopic expression of eyeless or mouse Pax6 in Drosophila results in the formation of additional eyes. Recently, another homeobox gene, Six3, was found to promote ectopic lens formation in fish embryos. The next step will be to unravel the associated regulatory pathways of these genes and assess the degree to which they display evolutionary conservation. This will be important in order to assimilate these findings with current anatomical and embryological models. It seems reasonable to believe that in the near future the characterization of the whole framework required for vertebrate eye development will be accomplished.

The early expression of the Pax4 gene, a member of the murine family of Pax genes, in a subset of endocrine progenitors is necessary for the differentiation of the beta and delta cell lineages. The gene is expressed in the early pancreas, but is later limited to beta cells. In the absence of Pax4, the presence of glucagon cells in considerably higher numbers indicates that in Pax4(super -1-) pancreas, a substantial amount of early endocrine precursors have acquired an alpha-cell phenotype. However, it may be possible that the absence of beta and delta cells leads to an increased proliferation of alpha-cell precursors.