Bcl-XL/Bax proteins direct the fate of embryonic cortical precursor cells

Mi Yoon Chang, Woong Sun, Wataru Ochiai, Kinichi Nakashima, Soo Young Kim, Chang Hwan Park, Jin Sun Kang, Jae Won Shim, A. Young Jo, Chun Sik Kang, Yong Sung Lee, Jae Sang Kim, Sang Hun Lee

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30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4293-4305
Number of pages13
JournalMolecular and cellular biology
Volume27
Issue number12
DOIs
Publication statusPublished - 2007 Jun

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Chang, M. Y., Sun, W., Ochiai, W., Nakashima, K., Kim, S. Y., Park, C. H., Kang, J. S., Shim, J. W., Jo, A. Y., Kang, C. S., Lee, Y. S., Kim, J. S., & Lee, S. H. (2007). Bcl-XL/Bax proteins direct the fate of embryonic cortical precursor cells. Molecular and cellular biology, 27(12), 4293-4305. https://doi.org/10.1128/MCB.00031-07