Timmer John, Chesnutt Catherine, Niswander Lee
Developmental Biology Program, Sloan-Kettering Institute, New York, NY 10021, USA.
Dev Biol. 2005 Sep 1;285(1):1-10. doi: 10.1016/j.ydbio.2005.05.039.
The generation of the appropriate types and numbers of mature neurons during the development of the spinal cord requires the careful coordination of patterning, proliferation, and differentiation. In the dorsal neural tube, this coordination is achieved by the combined action of multiple ligands of both the Wnt and TGF-beta families, and their effectors, such as the bHLH proteins. TGF-beta signaling acting through the BMP receptors is necessary for the generation of several dorsal interneuron types. Other TGF-beta ligands expressed in the dorsal neural tube interact with the Activin receptors, which signal via a different set of SMAD proteins than BMPs. The effects of Activin signaling on the developing neural tube have not been described. Here we have activated the Activin signal transduction pathway in a cell-autonomous manner in the developing chick neural tube. We find that a constitutively active Activin receptor promotes differentiation throughout the neural tube. Although most differentiated cell populations are unaffected by Activin signaling, the number of dorsal interneuron 3 (dI3) cells is specifically increased. Our data suggest that Activin signaling may promote the formation of the dI3 precursor cells within a region circumscribed by BMP signaling and that this function is not dependent upon BMP signaling.
脊髓发育过程中产生适当类型和数量的成熟神经元需要模式形成、增殖和分化的精确协调。在背侧神经管中，这种协调是通过Wnt和TGF-β家族的多种配体及其效应器（如bHLH蛋白）的联合作用实现的。通过BMP受体起作用的TGF-β信号传导对于几种背侧中间神经元类型的产生是必需的。在背侧神经管中表达的其他TGF-β配体与激活素受体相互作用，激活素受体通过与BMP不同的一组SMAD蛋白发出信号。激活素信号传导对发育中的神经管的影响尚未见报道。在这里，我们以细胞自主的方式在发育中的鸡神经管中激活了激活素信号转导途径。我们发现组成型激活的激活素受体促进整个神经管的分化。虽然大多数分化的细胞群体不受激活素信号传导的影响，但背侧中间神经元3（dI3）细胞的数量特异性增加。我们的数据表明，激活素信号传导可能促进在由BMP信号界定的区域内形成dI3前体细胞，并且该功能不依赖于BMP信号传导。
