BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities
BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities
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DOI：
10.7554/elife.30647
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发表时间：
2017-09-19
期刊：
影响因子：
7.7
通讯作者：
Butler, Samantha J.
中科院分区：
文献类型：
--
作者：
Andrews, Madeline G.;del Castillo, Lorenzo M.;Butler, Samantha J.
骨形态发生蛋白(BMP)家族在整个胚胎发育过程中反复发出信号，指示不同的细胞命运。在发育中的脊髓背侧，需要多个BMP来确定感觉中间神经元(INS)。以前的研究表明，BMP作为浓度依赖的形态因子来引导IN的识别，类似于声波刺猬在脊髓腹侧的模式。然而，多个BMP如何合作建立统一的形态梯度仍未解决。我们的研究支持另一种模型：BMP具有信号特异性活动，指导特定的IN命运。利用鸡和小鼠的模型，我们表明BMP配体的同一性，而不是浓度，指导着不同的背部同一性。单个BMP通过激活不同的I型BMP受体和不同的细胞周期调节来促进祖细胞构型或神经元分化。总而言之，这项研究表明，BMP信号的“混合和匹配”代码导致了不同类别的感觉INS。
The Bone Morphogenetic Protein (BMP) family reiteratively signals to direct disparate cellular fates throughout embryogenesis. In the developing dorsal spinal cord, multiple BMPs are required to specify sensory interneurons (INs). Previous studies suggested that the BMPs act as concentration -dependent morphogens to direct IN identity, analogous to the manner in which sonic hedgehog patterns the ventral spinal cord. However, it remains unresolved how multiple BMPs would cooperate to establish a unified morphogen gradient. Our studies support an alternative model: BMPs have signal-specific activities directing particular IN fates. Using chicken and mouse models, we show that the identity, not concentration, of the BMP ligand directs distinct dorsal identities. Individual BMPs promote progenitor patterning or neuronal differentiation by their activation of different type I BMP receptors and distinct modulations of the cell cycle. Together, this study shows that a 'mix and match' code of BMP signaling results in distinct classes of sensory INs.