Id sustains Hes1 expression to inhibit precocious neurogenesis by releasing negative autoregulation of Hes1.
Negative bHLH transcription factor Hes1 can inhibit neural stem cells (NSCs) from precocious neurogenesis through repressing proneural gene expression; therefore, sustenance of Hes1 expression is crucial for NSC pool maintenance. Here we find that Ids, the dominant-negative regulators of proneural proteins, are expressed prior to proneural genes and share an overlapping expression pattern with Hes1 in the early neural tube of chick embryos. Overexpression of Id2 in the chick hindbrain upregulates Hes1 expression and inhibits proneural gene expression and neuronal differentiation. By contrast, Hes1 expression decreases, proneural gene expression expands, and neurogenesis occurs precociously in Id1;Id3 double knockout mice and in Id1-3 RNAi-electroporated chick embryos. Mechanistic studies show that Id proteins interact directly with Hes1 and release the negative feedback autoregulation of Hes1 without interfering with its ability to affect other target genes. These results indicate that Id proteins participate in NSC maintenance through sustaining Hes1 expression in early embryos.
Laboratory of Molecular Cell Biology, Key Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Ge
G
Bai
Nengyin
N
Sheng
Zhihui
Z
Xie
Wei
W
Bian
Yoshifumi
Y
Yokota
Robert
R
Benezra
Ryoichiro
R
Kageyama
Francois
F
Guillemot
Naihe
N
Jing
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002454:Cell Differentiation; D002642:Chick Embryo; D015536:Down-Regulation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D051798:Inhibitor of Differentiation Protein 1 / Q000172:deficiency / Q000378:metabolism; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015854:Up-Regulation / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D051798:Inhibitor of Differentiation Protein 1; D051796:Inhibitor of Differentiation Proteins; C497455:Idb1 protein, mouse; C067679:Idb3 protein, mouse