Park M, Yaich L E, Bodmer R
Department of Biology, University of Michigan, Ann Arbor, MI 48109-1048, USA.
Mech Dev. 1998 Jul;75(1-2):117-26. doi: 10.1016/s0925-4773(98)00098-7.
In Drosophila, much has been learned about the specification of neuronal cell fates but little is known about the lineage of mesodermal cells with different developmental fates. Initially in development, individual mesodermal precursor cells are singled out to become the founder cells for specific muscles. The selection of muscle founder cells is thought to employ a Notch-mediated process of lateral inhibition, similar to what is observed for the specification of neural precursors. These muscle founder cells then seem to fuse with the surrounding, uncommitted myocytes inducing the formation of muscle fiber syncytia. In contrast, the differentiated progeny of neural precursor cells are usually the result of a fixed pattern of asymmetric cell divisions which are directed, in part, by interactions between numb, a localized intracellular-receptor protein, sanpodo (spdo), a potential tropomodulin homolog, and Notch, a transmembrane receptor protein. Here, we have investigated the role of these neural lineage genes in the cell fate specification of muscle and heart precursors. In particular, we have focused on a progenitor cell that is likely to produce a mixed lineage, generating both a pericardial heart cell and a somatic muscle founder cell. We show that the asymmetric segregation of Numb into one of these daughter cells antagonizes the function of Notch and spdo by preventing the presumptive muscle founder from assuming the same fate as its cardiac sibling. Our results suggest that asymmetric cell divisions, in addition to the previously-documented inductive mechanisms, play a major role in cardiac and somatic muscle patterning and that additionally the cytoskeleton may have a role in the asymmetrical localization of cell fate determinants.
在果蝇中，人们对神经细胞命运的特化已有很多了解，但对于具有不同发育命运的中胚层细胞谱系却知之甚少。在发育初期，单个中胚层前体细胞被挑选出来成为特定肌肉的起始细胞。肌肉起始细胞的选择被认为采用了一种由Notch介导的侧向抑制过程，这与神经前体细胞特化过程中所观察到的情况类似。这些肌肉起始细胞随后似乎与周围未分化的肌细胞融合，诱导形成肌纤维多核体。相比之下，神经前体细胞分化后的子代细胞通常是不对称细胞分裂固定模式的结果，这种分裂部分是由麻木蛋白（一种定位在细胞内的受体蛋白）、桑波多蛋白（spdo，一种潜在的原肌球蛋白同系物）和Notch（一种跨膜受体蛋白）之间的相互作用所引导的。在这里，我们研究了这些神经谱系基因在肌肉和心脏前体细胞命运特化中的作用。特别地，我们聚焦于一种可能产生混合谱系的祖细胞，它既能产生心包心脏细胞，也能产生体肌起始细胞。我们发现，麻木蛋白不对称地分离到其中一个子细胞中，通过阻止假定的肌肉起始细胞与其心脏同胞细胞具有相同的命运，从而拮抗了Notch和spdo的功能。我们的结果表明，除了先前记录的诱导机制外，不对称细胞分裂在心脏和体肌模式形成中起主要作用，并且细胞骨架可能在细胞命运决定因子的不对称定位中也发挥作用。
