BMPs 通过信号特异性而非形态发生活性来指导发育中脊髓感觉中间神经元的身份。

BMPs direct sensory interneuron identity in the developing spinal cord using signal-specific not morphogenic activities.

机构信息

Department of Neurobiology, University of California, Los Angeles, United States.

Neuroscience Graduate Program, University of California, Los Angeles, United States.

出版信息

Elife. 2017 Sep 19;6:e30647. doi: 10.7554/eLife.30647.

Abstract

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.

摘要

骨形态发生蛋白(BMP)家族在胚胎发生过程中反复发出信号,以指导不同的细胞命运。在发育中的背侧脊髓中,需要多种 BMP 来指定感觉神经元(INs)。先前的研究表明,BMP 作为浓度依赖性形态发生素发挥作用,以指导 IN 的身份,类似于 sonic hedgehog 模式化腹侧脊髓的方式。然而,多个 BMP 如何合作建立统一的形态发生素梯度仍未解决。我们的研究支持替代模型:BMP 具有信号特异性活性,指导特定的 IN 命运。使用鸡和鼠模型,我们表明,BMP 配体的身份,而不是浓度,决定了不同的背侧身份。单个 BMP 通过激活不同的 I 型 BMP 受体和对细胞周期的不同调节来促进祖细胞模式或神经元分化。总之,这项研究表明,BMP 信号的“混合和匹配”代码导致不同类别的感觉 INs。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbe2/5605194/336fff91f6cc/elife-30647-fig1.jpg

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