Open AccessBcl-XL/Bax Proteins Direct the Fate of Embryonic Cortical Precursor Cells
Author(s) -
Mi-Yoon Chang,
Woong Sun,
Wataru Ochiai,
Kinichi Nakashima,
SooYoung Kim,
Chang-Hwan Park,
Jungu Kang,
Jae Kun Shim,
A-Young Jo,
Chun-Sik Kang,
Yong-Sung Lee,
Jaesang Kim,
SangHun Lee
Publication year - 2007
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00031-07
Subject(s) - biology , neurogenesis , microbiology and biotechnology , embryonic stem cell , bcl xl , cellular differentiation , apoptosis , astrocyte , neural stem cell , bcl 2 associated x protein , programmed cell death , caspase 3 , stem cell , biochemistry , neuroscience , central nervous system , gene
In the developing mouse brain, the highest Bcl-XL expression is seen at the peak of neurogenesis, whereas the peak of Bax expression coincides with the astrogenic period. While such observations suggest an active role of the Bcl-2 family proteins in the generation of neurons and astrocytes, no definitive demonstration has been provided to date. Using combinations of gain- and loss-of-function assays in vivo and in vitro, we provide evidence for instructive roles of these proteins in neuronal and astrocytic fate specification. Specifically, in Bax knockout mice, astrocyte formation was decreased in the developing cortices. Overexpression of Bcl-XL and Bax in embryonic cortical precursors induced neural and astrocytic differentiation, respectively, while inhibitory RNAs led to the opposite results. Importantly, inhibition of caspase activity, dimerization, or mitochondrial localization of Bcl-XL /Bax proteins indicated that the differentiation effects of Bcl-XL /Bax are separable from their roles in cell survival and apoptosis. Lastly, we describe activation of intracellular signaling pathways and expression of basic helix-loop-helix transcriptional factors specific for the Bcl-2 protein-mediated differentiation.