HeyL promotes neuronal differentiation of neural progenitor cells.
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.
Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Ali
A
Jalali
Alexander G
AG
Bassuk
Lixin
L
Kan
Nipan
N
Israsena
Abhishek
A
Mukhopadhyay
Tammy
T
McGuire
John A
JA
Kessler
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000235:genetics; D001253:Astrocytes / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000254:growth & development; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D018797:Cell Cycle Proteins; D049452:Green Fluorescent Proteins; D011509:Proteoglycans; D014404:Tubulin; D000099216:Chondroitin Sulfate Proteoglycan 4; C525810:Bmp4 protein, mouse; C120420:Hey1 protein, mouse; C402588:Heyl protein, mouse; C462941:beta3 tubulin, mouse; C485184:enhanced green fluorescent protein
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