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Regulation of hippocampal neuronal differentiation by the basic helix‐loop‐helix transcription factors HES‐1 and MASH‐1
Author(s) -
Castella Paul,
Wagner John A.,
Caudy Michael
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990501)56:3<229::aid-jnr2>3.0.co;2-z
Subject(s) - biology , neurite , microbiology and biotechnology , transcription factor , activator (genetics) , repressor , hippocampal formation , basic helix loop helix , cellular differentiation , proneural genes , nerve growth factor , dna binding protein , gene , genetics , neuroscience , receptor , in vitro
HES‐1 is a vertebrate homologue of the Drosophila basic helix‐loop‐helix (bHLH) protein Hairy, a transcriptional repressor that negatively regulates neuronal differentiation. HES‐1 expression in neuronal precursors precedes and represses the expression of the neuronal commitment gene MASH‐1, a bHLH activator homologous to the proneural Achaete‐Scute genes in Drosophila. Down‐regulation of HES‐1 expression in developing neuroblasts may be necessary for the induction of a regulatory cascade of bHLH activator proteins that controls the commitment and progression of neuronal differentiation. Here we show that the differentiation of embryonic day‐17 rat hippocampal neurons in culture was coincident with a decline in HES‐1 expression and DNA binding. Therefore, we examined the effect of forced expression of HES‐1 and MASH‐1 upon nerve growth factor (NGF) ‐induced differentiation in TrkA transfected hippocampal neurons. Expression of HES‐1 inhibited both the intrinsic and NGF‐induced neurite outgrowth, whereas MASH‐1 expression increased neurite outgrowth. Strikingly, the increased hippocampal differentiation observed with MASH‐1 expression is completely blocked by coexpression of HES‐1. Furthermore, both wild‐type HES‐1 and a non‐DNA binding mutant of HES‐1 repressed MASH‐1‐dependent transcription activation. These results suggest that down‐regulation of HES‐1 is necessary for autonomous, growth facto‐ induced and MASH‐1‐activated hippocampal differentiation. J. Neurosci. Res. 56:229–240, 1999. © 1999 Wiley‐Liss, Inc.