BMP-4 induces a Smad-dependent apoptotic cell death of mouse embryonic stem cell-derived neural precursors
BMP-4 induces a Smad-dependent apoptotic cell death of mouse embryonic stem cell-derived neural precursors
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DOI：
10.1038/sj.cdd.4401799
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发表时间：
2006-07-01
影响因子：
12.4
通讯作者：
Rouleau, M.
中科院分区：
文献类型：
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作者：
Gambaro, K.;Aberdam, E.;Rouleau, M.
胚胎外胚层注定要成为神经或表皮，这取决于原肠胚形成之前和期间发生的模式化过程。据报道，表皮定型源于骨形态发生蛋白-4（BMP-4）依赖性对背外胚层神经化的抑制。我们最近证明，小鼠胚胎干细胞（ES）与BMP-4处理进行有效的角质形成细胞的承诺和表皮发生。我们关注BMP-4在早期选择神经和表皮定型中的确切作用，在此我们表明，BMP-4处理ES细胞导致Sox-1（+）神经前体细胞的急剧凋亡死亡，并伴随表皮定型。此外，Smad途径的中和防止BMP-4凋亡过程和神经分化的抑制。我们的研究结果表明，在哺乳动物中，BMP-4，作为一个积极的诱导表皮承诺，干扰神经前体细胞通过诱导其凋亡细胞死亡的生存。
Embryonic ectoderm is fated to become either neural or epidermal, depending on patterning processes that occur before and during gastrulation. It has been stated that epidermal commitment proceeds from a bone morphogenetic protein-4 (BMP-4)-dependent inhibition of dorsal ectoderm neuralization. We recently demonstrated that murine embryonic stem (ES) cells treated with BMP-4 undergo effective keratinocyte commitment and epidermogenesis. Focusing on the precise role of BMP-4 in the early choice between neural and epidermal commitment, we show here that BMP-4 treatment of ES cells leads to a dramatic apoptotic death of Sox-1(+) neural precursors with concomitant epidermal engagement. In addition, neutralization of the Smad pathway prevents both the BMP-4 apoptotic process and the inhibition of neural differentiation. Our results suggest that, in mammals, BMP-4, as an active inducer of epidermal commitment, interferes with the survival of neural precursors through induction of their apoptotic cell death.