Transcription factor Sox10 orchestrates activity of a neural crest-specific enhancer in the vicinity of its gene

The Sox10 transcription factor is a central regulator of vertebrate neural crest and nervous system development. Its expression is likely controlled by multiple enhancer elements, among them U3 (alternatively known as MCS4). Here we analyze U3 activity to obtain deeper insights into Sox10 function and expression in the neural crest and its derivatives. U3 activity strongly depends on the presence of Sox10 that regulates its own expression as commonly observed for important developmental regulators. Sox10 bound directly as monomer to at least three sites in U3, whereas a fourth site preferred dimers. Deletion of these sites efficiently reduced U3 activity in transfected cells and transgenic mice. In stimulating the U3 enhancer, Sox10 synergized with many other transcription factors present in neural crest and developing peripheral nervous system including Pax3, FoxD3, AP2α, Krox20 and Sox2. In case of FoxD3, synergism involved Sox10-dependent recruitment to the U3 enhancer, while Sox10 and AP2α each had to bind to the regulatory region. Our study points to the importance of autoregulatory activity and synergistic interactions for maintenance of Sox10 expression and functional activity of Sox10 in the neural crest regulatory network

Insights into olfactory ensheathing cell development from a laser-microdissection and transcriptome-profiling approach.

Olfactory ensheathing cells (OECs) are neural crest-derived glia that ensheath bundles of olfactory axons from their peripheral origins in the olfactory epithelium to their central targets in the olfactory bulb. We took an unbiased laser microdissection and differential RNA-seq approach, validated by in situ hybridization, to identify candidate molecular mechanisms underlying mouse OEC development and differences with the neural crest-derived Schwann cells developing on other peripheral nerves. We identified 25 novel markers for developing OECs in the olfactory mucosa and/or the olfactory nerve layer surrounding the olfactory bulb, of which 15 were OEC-specific (that is, not expressed by Schwann cells). One pan-OEC-specific gene, Ptprz1, encodes a receptor-like tyrosine phosphatase that blocks oligodendrocyte differentiation. Mutant analysis suggests Ptprz1 may also act as a brake on OEC differentiation, and that its loss disrupts olfactory axon targeting. Overall, our results provide new insights into OEC development and the diversification of neural crest-derived glia.Cambridge Commonwealth Trust Cambridge Philosophical Societ

Reporters for the analysis of N-glycosylation in Candida albicans

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Phox2b function in the enteric nervous system is conserved in zebrafish and is sox10-dependent

Zebrafish lacking functional sox10 have defects in non-ectomesenchymal neural crest derivatives including the enteric nervous system (ENS) and as such provide an animal model for human Waardenburg Syndrome IV. Here, we characterize zebrafish phox2b as a functionally conserved marker of the developing ENS. We show that morpholino-mediated knockdown of Phox2b generates fish modeling Hirschsprung disease. Using markers, including phox2b, we investigate the ontogeny of the sox10 ENS phenotype. As previously shown for melanophore development, ENS progenitor fate specification fails in these mutant fish. However, in addition, we trace back the sox10 mutant ENS defect to an even earlier time point, finding that most neural crest cells fail to migrate ventrally to the gut primordium. (c) 2005 Elsevier Ireland Ltd. All rights reserved.Medical Research Council [G0300415

GUDMAP - An Online GenitoUrinary Resource

The GenitoUrinary Development Molecular Anatomy Project (GUDMAP) is a consortium of laboratories working to provide the scientific and medical community with gene expression data and tools to facilitate research (see "www.gudmap.org":http://www.gudmap.org). The data provided by GUDMAP includes large _in situ_ hybridization screens (wholemount and section) and expression microarray analysis of components of the developing mouse urogenital system (including laser-captured material and FACS-isolated cells from transgenic reporter mice). In addition, a high-resolution anatomy ontology has been developed by members of the GUDMAP consortium to describe the subcompartments of the developing murine genitourinary tract. 

The GUDMAP Database Development Team and Editorial Office - both based in Edinburgh - function to ensure submission, curation, storage and presentation of the data submitted by the GUDMAP consortium. Our collective aim is twofold: 1) to simplify the process of submission so that data is publically available as soon as it is produced; and 2) to organize this information in a database and ensure that the online interface is continuously available and easy to use. Thus far, we have developed a range of tools that help both the submitter and the end user. These include: an online annotation tool that simplifies _in situ_ data submission through an ontology-based graphical user interface; a database interface that allows users to browse and query expression data, and to filter data by organ system; a heat-map display of microarray data and analyses. Furthermore, the Edinburgh team has developed a GUDMAP Disease Database that queries associations between genes, genitourinary diseases, and renal/urinary and reproductive phenotypes. In collaboration with GUDMAP consortium members at the CCHMC (Cincinnati Children's Hospital Medical Center), the Disease Database is being extended to include mammalian phenotypes mapped to OMIM entries. 

By virtue of its impressive dataset and its ease of use we hope that the GUDMAP Website will continue to serve as a powerful resource for biologists, clinicians and bioinformaticians with an interest in the urogenital system

A curated online resource for SOX10 and pigment cell molecular genetic pathways

We describe the creation of a specialized web-accessible database named the Pigment Cell Gene Resource, which contains information on the genetic pathways that regulate pigment cell development and function. This manually curated database is comprised of two sections, an annotated literature section and an interactive transcriptional network diagram. Initially, this database focuses on the transcription factor SOX10, which has essential roles in pigment cell development and function, but the database has been designed with the capacity to expand in the future, allowing inclusion of many more pigmentation genes

Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease

The transcription factor Sox5 modulates Sox10 function during melanocyte development

The transcription factor Sox5 has previously been shown in chicken to be expressed in early neural crest cells and neural crest-derived peripheral glia. Here, we show in mouse that Sox5 expression also continues after neural crest specification in the melanocyte lineage. Despite its continued expression, Sox5 has little impact on melanocyte development on its own as generation of melanoblasts and melanocytes is unaltered in Sox5-deficient mice. Loss of Sox5, however, partially rescued the strongly reduced melanoblast generation and marker gene expression in Sox10 heterozygous mice arguing that Sox5 functions in the melanocyte lineage by modulating Sox10 activity. This modulatory activity involved Sox5 binding and recruitment of CtBP2 and HDAC1 to the regulatory regions of melanocytic Sox10 target genes and direct inhibition of Sox10-dependent promoter activation. Both binding site competition and recruitment of corepressors thus help Sox5 to modulate the activity of Sox10 in the melanocyte lineage

Cranial neural crest cell contribution to craniofacial formation, pathology, and future directions in tissue engineering

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108634/1/bdrc21075.pd