title: Bcl-XL/Bax proteins direct the fate of embryonic cortical precursor cells.
abstract: In the developing mouse brain, the highest Bcl-X(L) 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-X(L) 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-X(L)/Bax proteins indicated that the differentiation effects of Bcl-X(L)/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.
authors: Department of Biochemistry & Molecular Biology, College of Medicine, Hanyang University, 17 Haengdang-Dong, Sungdong-Gu, Seoul, South Korea.
authors: Mi-Yoon
authors: MY
authors: Chang
authors: Woong
authors: W
authors: Sun
authors: Wataru
authors: W
authors: Ochiai
authors: Kinichi
authors: K
authors: Nakashima
authors: Soo-Young
authors: SY
authors: Kim
authors: Chang-Hwan
authors: CH
authors: Park
authors: Jin Sun
authors: JS
authors: Kang
authors: Jae-Won
authors: JW
authors: Shim
authors: A-Young
authors: AY
authors: Jo
authors: Chun-Sik
authors: CS
authors: Kang
authors: Yong-Sung
authors: YS
authors: Lee
authors: Jae-Sang
authors: JS
authors: Kim
authors: Sang-Hun
authors: SH
authors: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D061945:Caspase Inhibitors; D002454:Cell Differentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology*; D020099:Coated Materials, Biocompatible / Q000378:metabolism; D003433:Crosses, Genetic; D019281:Dimerization; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000166:cytology / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014161:Transduction, Genetic; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D061945:Caspase Inhibitors; D020099:Coated Materials, Biocompatible; D005353:Fibronectins; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein