Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system.
The developing central nervous system is partitioned into compartments by boundary cells, which have different properties than compartment cells, such as forming neuron-free zones, proliferating more slowly and acting as organizing centers. We now report that in mice the bHLH factor Hes1 is persistently expressed at high levels by boundary cells but at variable levels by non-boundary cells. Expression levels of Hes1 display an inverse correlation to those of the proneural bHLH factor Mash1, suggesting that downregulation of Hes1 leads to upregulation of Mash1 in non-boundary regions, whereas persistent and high Hes1 expression constitutively represses Mash1 in boundary regions. In agreement with this notion, in the absence of Hes1 and its related genes Hes3 and Hes5, proneural bHLH genes are ectopically expressed in boundaries, resulting in ectopic neurogenesis and disruption of the organizing centers. Conversely, persistent Hes1 expression in neural progenitors prepared from compartment regions blocks neurogenesis and reduces cell proliferation rates. These results indicate that the mode of Hes1 expression is different between boundary and non-boundary cells, and that persistent and high levels of Hes1 expression constitutively repress proneural bHLH gene expression and reduce cell proliferation rates, thereby forming boundaries that act as the organizing centers.
Baek
Joung Hee
JH
Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Kyoto 606-8507, Japan.
Hatakeyama
Jun
J
Sakamoto
Susumu
S
Ohtsuka
Toshiyuki
T
Kageyama
Ryoichiro
R
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D018929:Cell Culture Techniques; D002455:Cell Division; D047108:Embryonic Development; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009424:Nervous System Physiological Phenomena; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology* / Q000254:growth & development*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D000072056:Transcription Factor HES-1
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse