Wildner Hendrik, Müller Thomas, Cho Seo-Hee, Bröhl Dominique, Cepko Constance L, Guillemot Francois, Birchmeier Carmen
Max-Delbrück-Centrum for Molecular Medicine, Berlin-Buch, Germany.
Development. 2006 Jun;133(11):2105-13. doi: 10.1242/dev.02345.
dILA and dILB neurons comprise the major neuronal subtypes generated in the dorsal spinal cord, and arise in a salt-and-pepper pattern from a broad progenitor domain that expresses the bHLH factor Mash1. In this domain, Mash1-positive and Mash1-negative cells intermingle. Using a Mash1(GFP) allele in mice, we show here that Mash1+ progenitors give rise to dILA and dILB neurons. Using retroviral tracing in the chick, we demonstrate that a single progenitor can give rise to a dILA and a dILB neuron, and that dILA neurons are the product of asymmetric progenitor cell divisions. In Mash1-null mutant mice, the development of dILA, but not of dILB neurons is impaired. We provide evidence that a dual function of Mash1 in neuronal differentiation and specification accounts for the observed changes in the mutant mice. Our data allow us to assign to Mash1 a function in asymmetric cell divisions, and indicate that the factor coordinates cell cycle exit and specification in the one daughter that gives rise to a dILA neuron.
dILA和dILB神经元是脊髓背侧产生的主要神经元亚型，以一种黑白相间的模式从一个表达bHLH因子Mash1的广泛祖细胞区域产生。在这个区域中，Mash1阳性和Mash1阴性细胞相互混杂。利用小鼠中的Mash1(GFP)等位基因，我们在此表明Mash1+祖细胞产生dILA和dILB神经元。利用鸡胚中的逆转录病毒追踪，我们证明单个祖细胞可以产生一个dILA神经元和一个dILB神经元，并且dILA神经元是不对称祖细胞分裂的产物。在Mash1基因敲除的突变小鼠中，dILA神经元的发育受损，但dILB神经元的发育不受影响。我们提供的证据表明，Mash1在神经元分化和特化中的双重功能解释了在突变小鼠中观察到的变化。我们的数据使我们能够赋予Mash1在不对称细胞分裂中的功能，并表明该因子协调产生dILA神经元的一个子代细胞的细胞周期退出和特化。
