Roles of Hes genes in neural development.
Hes genes are mammalian homologues of Drosophila hairy and Enhancer of split, which encode basic helix-loop-helix (bHLH) transcriptional repressors. In the developing central nervous system, Hes1, Hes3 and Hes5 are highly expressed by neural stem cells. Inactivation of these Hes genes leads to upregulation of proneural genes, acceleration of neurogenesis and premature depletion of neural stem cells. Conversely, overexpression of Hes genes leads to inhibition of neurogenesis and maintenance of neural stem cells. At later stages of development, Hes genes promote gliogenesis. Furthermore, Hes genes regulate maintenance of boundaries, which partition the nervous system into many compartments and endow the neighboring compartments with regional identities by secreting morphogens. Boundary cells usually proliferate slowly and do not give rise to neurons, unlike neural stem cells in compartments. Interestingly, these different characteristics between boundary cells and compartmental neural stem cells are regulated by different modes of Hes1 expression, which is variable in neural stem cells in compartments and persistent and high in boundary cells. Thus, Hes genes play an essential role in neural development by regulating proliferation, differentiation and specification of neural stem cells.
Kageyama
Ryoichiro
R
Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, and Japan Science and Technology Agency, CREST, Kyoto 606-8507, Japan. rkageyam@virus.kyoto-u.ac.jp
Ohtsuka
Toshiyuki
T
Kobayashi
Taeko
T
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015509:Developmental Biology / Q000379:methods*; D029721:Drosophila Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008957:Models, Genetic; D009420:Nervous System / Q000196:embryology*; D009474:Neurons / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D008024:Ligands; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C489235:hairy protein, Drosophila; C077478:HES5 protein, human; C078493:HES1 protein, human