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Orphan Nuclear Receptor, GCNF, Is Required for Early Neural Crest Cell Induction and Survival
Author(s) -
Munoz William A,
Bhatt Shachi,
CraneDennis Jennifer,
Achilleos Annita,
Sakai Daisuke,
Cooney Austin,
Trainor Paul
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.394.3
Subject(s) - neural crest , biology , cell fate determination , microbiology and biotechnology , nuclear receptor , population , neuroscience , genetics , embryo , transcription factor , gene , demography , sociology
Neural crest cells (NCC) are considered to be a vertebrate innovation that significantly contributed to the evolution, predation, radiation and adaptation of vertebrates to most niches of the planet. NCC comprise a unique vertebrate cell population that is frequently termed the “fourth germ layer” because they form in conjunction with the other germ layers and give rise to a diverse array of cell types and tissues including most of the craniofacial skeleton, peripheral nervous system, and pigment cells amongst many others. NCC development is dependent on gene regulatory network (GRN) control of several cellular mechanisms including induction, migration and differentiation. Defects in these processes result in clinical manifestations termed neurocristopathies. In contrast to aquatic and avian species, we currently have a very poor understanding of the factors that regulate mammalian neural crest cell induction and specification. Here we describe molecular analyses in mouse models that reveal a critical role for the orphan nuclear receptor, Germ cell nuclear factor ( Gcnf/Nr6a1 ) in mammalian neural crest cell formation and survival. Comparison of null and conditional Gcnf mutant embryos indicates that Gcnf is required prior to E8.0 for proper neural crest cell specification and induction. Furthermore, Gcnf functions as a bimodal switch to repress neural stem cell fate and promote the acquisition of neural crest cell identity. Thus our findings have identified a novel regulator of mammalian neural crest cell development and defined a temporal window for mammalian neural crest cell formation which is earlier than previously thought and raises important questions regarding the appropriateness of Wnt1Cre in studies of mammalian neural crest cell specification and induction. Support or Funding Information This work in the Trainor lab is supported by the Stowers Institute for Medical Research, the March of Dimes (#6‐FY08‐265) and the National Institute of Health ‐ National Institute for Dental and Craniofacial Research (DE016082). WIM is further supported by the American Association of Anatomist Postdoctoral Fellowship.