Mash1 is required for generic and subtype differentiation of hypothalamic neuroendocrine cells

David McNay, Michelle Pelling, Suzanne Claxton, François Guillemot, Siew-Lan Ang

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The neuroendocrine hypothalamus regulates a number of critical biological processes and underlies a range of diseases from growth failure to obesity. Although the elucidation of hypothalamic function has progressed well, knowledge of hypothalamic development is poor. In particular, little is known about the processes underlying the neurogenesis and specification of neurons of the ventral nuclei, the arcuate and ventromedial nuclei. The proneural gene Mash1 is expressed throughout the basal retrochiasmatic neuroepithelium and loss of Mash1 results in hypoplasia of both the arcuate and ventromedial nuclei. These defects are due to a failure of neurogenesis and apoptosis, a defect that can be rescued by ectopic Ngn2 under the control of the Mash1 promoter. In addition to its role in neurogenesis, analysis of Mash1(-/-), Mash1(+/-), Mash1(KINgn2/KINgn2), and Mash1(KINgn2/+) mice demonstrates that Mash1 is specifically required for Gsh1 expression and subsequent GHRH expression, positively regulates SF1 expression, and suppresses both tyrosine hydroxylase (TH) and neuropeptide Y (NPY) expression. Although Mash1 is not required for propiomelanocortin (POMC) expression, it is required for normal development of POMC(+) neurons. These data demonstrate that Mash1 is both required for the generation of ventral neuroendocrine neurons as well as playing a central role in subtype specification of these neurons.
Original languageEnglish
Pages (from-to)1623-1632
Number of pages10
JournalMolecular Endocrinology
Volume20
Issue number7
Early online date9 Feb 2006
DOIs
Publication statusPublished - 1 Jul 2006

Keywords

  • animals
  • arcuate nucleus
  • basic helix-loop-helix transcription factors
  • body weight
  • cell differentiation
  • DNA-binding proteins
  • gene expression
  • growth hormone-releasing hormone
  • hypothalamus
  • loss of heterozygosity
  • mice
  • neuroepithelial cells
  • neurons
  • neuropeptide Y
  • optic chiasm
  • organ specificity
  • pro-opiomelanocortin
  • transcription factors
  • tyrosine 3-monooxygenase
  • up-regulation
  • ventral thalamic nuclei
  • ventromedial hypothalamic nucleus

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