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HeyL promotes neuronal differentiation of neural progenitor cells
Author(s) -
Jalali Ali,
Bassuk Alexander G.,
Kan Lixin,
Israseipan,
Mukhopadhyay Abhishek,
McGuire Tammy,
Kessler John A.
Publication year - 2011
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/jnr.22562
Subject(s) - hes1 , proneural genes , biology , notch signaling pathway , progenitor cell , neurogenesis , microbiology and biotechnology , neural stem cell , progenitor , cellular differentiation , embryonic stem cell , stem cell , genetics , signal transduction , gene
Members of the Hes and Hey families of basic helix‐loop‐helix transcription factors are regarded as Notch target genes that generally inhibit neuronal differentiation of neural progenitor cells. We found that HeyL, contrary to the classic function of Hes and Hey factors, promotes neuronal differentiation of neural progenitor cells both in culture and in the embryonic brain in vivo. Furthermore, null mutation of HeyL decreased the rate of neuronal differentiation of cultured neural progenitor cells. HeyL binds to and activates the promoter of the proneural gene neurogenin2, which is inhibited by other Hes and Hey family members, and HeyL is a weak inhibitor of the Hes1 promoter. HeyL is able to bind other Hes and Hey family members, but it cannot bind the Groucho/Tle1 transcriptional corepressor, which mediates the inhibitory effects of the Hes family of factors. Furthermore, although HeyL expression is only weakly augmented by Notch signaling, we found that bone morphogenic protein signaling increases HeyL expression by neural progenitor cells. These observations suggest that HeyL promotes neuronal differentiation of neural progenitor cells by activating proneural genes and by inhibiting the actions of other Hes and Hey family members. ©2011 Wiley‐Liss, Inc.