Abstract
In the embryonic neural plate, a subset of precursor cells with neurogenic potential differentiates into neurons. This process of primary neurogenesis requires both the specification of cells for neural differentiation, regulated by Notch signaling, and the activity of neurogenic transcription factors such as neurogenin and NeuroD which drive the program of neural gene expression. Here we study the role of Hes6, a member of the hairy enhancer of split family of transcription factors, in primary neurogenesis in Xenopus embryos. Hes6 is an atypical Hes gene in that it is not regulated by Notch signaling and promotes neural differentiation in mouse cell culture models. We show that depletion of Xenopus Hes6 (Xhes6) by morpholino antisense oligonucleotides results in a failure of neural differentiation, a phenotype rescued by both wild type Xhes6 and a Xhes6 mutant unable to bind DNA. However, an Xhes6 mutant that lacks the ability to bind Groucho/TLE transcriptional co-regulators is only partly able to rescue the phenotype. Further analysis reveals that Xhes6 is essential for the induction of neurons by both neurogenin and NeuroD, acting via at least two distinct mechanisms, the inhibition of antineurogenic Xhairy proteins and by interaction with Groucho/TLE family proteins. We conclude Xhes6 is essential for neurogenesis in vivo, acting via multiple mechanisms to relieve inhibition of proneural transcription factor activity within the neural plate.
Highlights
During development, neural specification delineates the neural plate from the surrounding ectoderm that is destined to form epidermis
By using antisense morpholino oligonucleotides to deplete Xenopus Hes6 (Xhes6) we demonstrate it is essential for neurogenesis early Xenopus embryos
Consistent with previous reports, we find that Xhes6 is expressed strongly in the posterior region of neurula stage embryos, but is present in the medial and lateral domains of the neural plate and at low levels anteriorly
Summary
Neural specification delineates the neural plate from the surrounding ectoderm that is destined to form epidermis. A key step in neurogenesis is expression and activity of the basic helix-loop-helix proneural transcription factors that both specify the neuronal lineage and drive neuronal differentiation. Neurogenin induces the transcription of a range of target genes implicated in neurogenesis [7], and is required for neural commitment in Xenopus, Zebra Fish and mouse, as when the protein is depleted or absent cells that would normally form neurons adopt glial fate [8,9,10]. Overexpression of Neurogenin drives cells into the neural lineage in Xenopus, chick shares four highly conserved domains with other Hes proteins: a basic domain required for DNA binding, a Helix loop helix domain required for protein dimerization, an orange domain by which it binds to other Hes proteins and a C-teminal WRPW motif that recruits the Groucho/TLE family transcriptional corepressor proteins (Fig. 1) [26]. The sequence of the Hes loop domain is distinct from other Hes proteins giving it distinctive
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
