0 Patent citations 102 Scholarly citations Reference Count: 57
Joung Hee Baek;Jun Hatakeyama;Susumu Sakamoto;Toshiyuki Ohtsuka;Ryoichiro Kageyama
The developing central nervous system is partitioned into compartments byboundary cells, which have different properties than compartment cells, suchas forming neuron-free zones, proliferating more slowly and acting asorganizing centers. We now report that in mice the bHLH factor Hes1 ispersistently expressed at high levels by boundary cells but at variable levelsby non-boundary cells. Expression levels of Hes1 display an inversecorrelation to those of the proneural bHLH factor Mash1, suggesting thatdownregulation of Hes1 leads to upregulation of Mash1 in non-boundary regions,whereas persistent and high Hes1 expression constitutively represses Mash1 inboundary regions. In agreement with this notion, in the absence of Hes1 and its related genes Hes3 and Hes5 , proneuralbHLH genes are ectopically expressed in boundaries, resulting in ectopicneurogenesis and disruption of the organizing centers. Conversely, persistentHes1 expression in neural progenitors prepared from compartment regions blocksneurogenesis and reduces cell proliferation rates. These results indicate thatthe mode of Hes1 expression is different between boundary and non-boundarycells, and that persistent and high levels of Hes1 expression constitutivelyrepress proneural bHLH gene expression and reduce cell proliferation rates,thereby forming boundaries that act as the organizing centers.
Kyoto University;Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Kyoto 606-8507, Japan.Kyoto UniversityKyoto UniversityKyoto UniversityKyoto University