Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype
Multiple roles of bone morphogenetic protein signaling in the regulation of cortical cell number and phenotype
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DOI：
10.1523/jneurosci.19-16-07077.1999
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发表时间：
1999-08-15
影响因子：
5.3
通讯作者：
Kessler, JA
中科院分区：
文献类型：
--
作者：
Mabie, PC;Mehler, MF;Kessler, JA
骨形态发生蛋白（BMP）家族的成员在中枢神经系统和周围神经系统的神经发育的多个方面都有牵连。BMP配体和受体以及BMP拮抗剂noggin在发育中的大脑皮层中表达，使BMP可能成为调节皮层发育的候选者。为了确定这些因素在大脑皮层发育中的作用，我们在体外检测了BMP2和BMP4对皮质细胞的影响。从胚胎第13天（E13）和E16天的大鼠大脑皮层中培养细胞，在缺乏或存在不同浓度的成纤维细胞生长因子2（一种已知的皮质细胞增殖和分化的调节剂）的情况下培养细胞。在E13时，BM Ps促进细胞死亡，抑制皮质心室带细胞的增殖，导致神经元减少，未产生胶质细胞。在E16时，bmp的作用更为复杂。BMP2浓度在1-10 ng/ml范围内可促进神经元和星形胶质细胞的分化，抑制少突胶质细胞的分化，而100 ng/ml BMP2可促进细胞死亡，抑制细胞增殖。添加BMP拮抗剂noggin促进体外少突胶质细胞的形成，表明内源性BMP信号影响体外皮质细胞的分化。BMP2和noggin在皮质发育中的分布表明，配体和拮抗剂的局部浓度决定了皮质发生过程中BMP信号的梯度。总之，这些结果支持了bmp及其拮抗剂noggin共同调节皮质细胞命运和形态发生的假设。
Members of the bone morphogenetic protein (BMP) family have been implicated in multiple aspects of neural development in both the CNS and peripheral nervous system. BMP ligands and receptors, as well as the BMP antagonist noggin, are expressed in the developing cerebral cortex, making the BMPs likely candidates for regulating cortical development. To define the role of these factors in the developing cerebral cortex, we examined the effects of BMP2 and BMP4 on cortical cells in vitro. Cells were cultured from embryonic day 13 (E13) and E16 rat cerebral cortex in the absence or presence of different concentrations of fibroblast growth factor 2, a known regulator of cortical cell proliferation and differentiation. At E13, the BM Ps promoted cell death and inhibited proliferation of cortical ventricular zone cells, resulting in the generation of fewer neurons and no glia. At E16, the effects of the BMPs were more complex. Concentrations of BMP2 in the range of 1-10 ng/ml promoted neuronal and astroglial differentiation and inhibited oligodendroglial differentiation, whereas 100 ng/ml BMP2 promoted cell death and inhibited proliferation. Addition of the BMP antagonist noggin promoted oligodendrogliogenesis in vitro, demonstrating that endogenous BMP signaling influences the differentiation of cortical cells in vitro. The distribution of BMP2 and noggin within the developing cortex suggests that local concentrations of ligands and antagonists define gradients of BMP signaling during corticogenesis. Together, these results support the hypothesis that the BMPs and their antagonist noggin co-regulate cortical cell fate and morphogenesis.