Lo L, Sommer L, Anderson D J
Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
Curr Biol. 1997 Jun 1;7(6):440-50. doi: 10.1016/s0960-9822(06)00191-6.
The interplay between growth factors and transcription factors in vertebrate neurogenesis is poorly understood. MASH1 is a basic helix-loop-helix (bHLH) transcription factor that is essential for autonomic neurogenesis. Bone morphogenetic protein (BMP) 2, and its relative BMP4, have been shown to induce expression of MASH1 and to promote autonomic neuronal differentiation in neural crest stem cells. The relationship between expression of MASH1 and the neurogenic competence of neural crest cells has not been investigated, however.
We have examined the function of MASH1 in neurogenic competence using a population of immuno-isolated neural-crest-derived progenitor cells. Post-migratory neural crest cells isolated from fetal rat gut expressed Mash1, yet comprised a mixture of committed neuronal precursors and non-neuronal cells. The non-neuronal cells remained competent to differentiate to neurons, however, if challenged with BMP2. Such competence declines with time and is paralleled by a decline in Mash1 expression in the cells. Expression of endogenous Mash1 can be maintained by BMP2; in turn, constitutive expression of Mash1 from a retroviral vector maintains competence for neuronal differentiation in response to late addition of BMP2.
These data suggest that MASH1 promotes competence for neurogenesis, in a manner similar to its homologs, the proneural genes achaete-scute in Drosophila. They also reveal an unexpected feedback interaction between BMP2 and MASH1 during neuronal differentiation. MASH1 may play multiple roles at successive stages of development within a neurogenic lineage, only one of which is revealed by a loss-of-function mutation.
在脊椎动物神经发生过程中，生长因子与转录因子之间的相互作用尚不清楚。MASH1是一种碱性螺旋-环-螺旋（bHLH）转录因子，对自主神经发生至关重要。骨形态发生蛋白（BMP）2及其相关蛋白BMP4已被证明可诱导MASH1的表达，并促进神经嵴干细胞的自主神经元分化。然而，MASH1的表达与神经嵴细胞的神经发生能力之间的关系尚未得到研究。
我们使用一群免疫分离的神经嵴来源的祖细胞研究了MASH1在神经发生能力中的功能。从胎鼠肠道分离的迁移后神经嵴细胞表达Mash1，但包含已定向的神经元前体细胞和非神经元细胞的混合物。然而，如果用BMP2刺激，非神经元细胞仍有分化为神经元的能力。这种能力会随着时间下降，并且与细胞中Mash1表达的下降平行。内源性Mash1的表达可由BMP2维持；反过来，来自逆转录病毒载体的Mash1的组成型表达维持了对后期添加BMP2的神经元分化能力。
这些数据表明，MASH1以类似于其同源物果蝇神经原基因achaete-scute的方式促进神经发生能力。它们还揭示了在神经元分化过程中BMP2和MASH1之间意想不到的反馈相互作用。MASH1可能在神经发生谱系发育的连续阶段发挥多种作用，其中只有一种作用可通过功能丧失突变揭示。
