Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms

Carina Hanashima, Lijian Shen, Suzanne C. Li, Eseng Lai

研究成果: Article

131 引用 (Scopus)

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The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1NHAA. The BF1NHAA protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1 NHAA protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.

元の言語English
ページ(範囲)6526-6536
ページ数11
ジャーナルJournal of Neuroscience
22
発行部数15
DOI
出版物ステータスPublished - 2002 8 1
外部発表Yes

ASJC Scopus subject areas

  • Neuroscience(all)

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