Panchision D M, Pickel J M, Studer L, Lee S H, Turner P A, Hazel T G, McKay R D
Laboratory of Molecular Biology, NINDS, National Institutes of Health, Bethesda, Maryland 20892-4092, USA.
Genes Dev. 2001 Aug 15;15(16):2094-110. doi: 10.1101/gad.894701.
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 Bmpr-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.
骨形态发生蛋白（BMPs）在胚胎发育过程中具有多样且有时相互矛盾的作用。为了确定BMP作用的潜在机制，我们在体外和体内分析了两种BMP受体BMPR-IA和BMPR-IB在神经前体细胞中的表达和功能。神经前体细胞始终表达Bmpr-1a，但Bmpr-1b直到胚胎第9天才表达，并且局限于围绕BMP配体来源的背侧神经管。BMPR-IA激活诱导（而音猬因子抑制）前体细胞中Bmpr-1b以及背侧身份基因的表达，并促进其增殖。当BMPR-IB被激活时，它通过导致有丝分裂停滞来限制前体细胞数量。这在妊娠早期胚胎中导致细胞凋亡，在妊娠中期胚胎中导致终末分化。因此，基于BMPR-IB相对于BMPR-IA的积累，BMP的作用先是诱导性的（通过BMPR-IA），然后是终止性的（通过BMPR-IB）。我们描述了一种前馈机制，以解释这些受体的顺序作用如何控制神经干细胞产生背侧前体细胞及其命运。
