Sequential actions of BMP receptors control neural precursor cell production and fate
Sequential actions of BMP receptors control neural precursor cell production and fate
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DOI：
10.1101/gad.894701
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发表时间：
2001-08-15
影响因子：
10.5
通讯作者：
McKay, RDG
中科院分区：
文献类型：
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作者：
Panchision, DM;Pickel, JM;McKay, RDG
骨形态发生蛋白（BMP）在胚胎发育过程中具有多种多样的，有时是自相矛盾的作用。为了确定BMP作用的机制，我们分析了两种BMP受体BMPR-IA和BMPR-IB在体外和体内神经前体细胞中的表达和功能。神经前体细胞总是表达Bmpr-1a，但Bmpr-1b直到胚胎第9天才表达，并且仅限于BMP配体来源周围的背侧神经管。BMPR-IA激活诱导（和Sonic hedgehog阻止）前体细胞中RMPR-1b沿着背侧身份基因的表达，并促进其增殖。当BMPR-IB被激活时，它通过引起有丝分裂停滞来限制前体细胞的数量。这导致妊娠早期胚胎的细胞凋亡和妊娠中期胚胎的终末分化。因此，基于BMPR-IB相对于BMPR-IA的积累，BMP作用首先诱导（通过BMPR-IA），然后终止（通过BMPR-IB）。我们描述了一种前馈机制来解释这些受体的顺序作用如何控制神经干细胞的背前体细胞的产生和命运。
Bone morphogenetic proteins (BMPs) have diverse and sometimes paradoxical effects during embryonic development. To determine the mechanisms underlying BMP actions, we analyzed the expression and function of two BMP receptors, BMPR-IA and BMPR-IB, in neural precursor cells in vitro and in vivo. Neural precursor cells always express Bmpr-1a, but Bmpr-1b is not expressed until embryonic day 9 and is restricted to the dorsal neural tube surrounding the source of BMP ligands. BMPR-IA activation induces (and Sonic hedgehog prevents) expression of Rmpr-1b along with dorsal identity genes in precursor cells and promotes their proliferation. When BMPR-IB is activated, it limits precursor cell numbers by causing mitotic arrest. This results in apoptosis in early gestation embryos and terminal differentiation in mid-gestation embryos. Thus, BMP actions are first inducing (through BMPR-IA) and then terminating (through BMPR-IB), based on the accumulation of BMPR-IB relative to BMPR-IA. We describe a feed-forward mechanism to explain how the sequential actions of these receptors control the production and fate of dorsal precursor cells from neural stem cells.