Frank C Andrew, Hawkins Nancy C, Guenther Catherine, Horvitz H Robert, Garriga Gian
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3204, USA.
Dev Biol. 2005 Aug 15;284(2):301-10. doi: 10.1016/j.ydbio.2005.05.026.
Asymmetric cell division occurs when a mother cell divides to generate two distinct daughter cells, a process that promotes the generation of cellular diversity in metazoans. During Caenorhabditis elegans development, the asymmetric divisions of neural progenitors generate neurons, neural support cells and apoptotic cells. C. elegans HAM-1 is an asymmetrically distributed cortical protein that regulates several of these asymmetric neuroblast divisions. Here, we show that HAM-1 is a novel protein and define residues important for HAM-1 function and distribution to the cell cortex. Our phenotypic analysis of ham-1 mutant embryos suggests that HAM-1 controls only neuroblast divisions that produce apoptotic cells. Moreover, ham-1 mutant embryos contain many unusually large cell-death corpses. An investigation of this corpse phenotype revealed that it results from a reversal of neuroblast polarity. A misplacement of the neuroblast cleavage plane generates daughter cells of abnormal size, with the apoptotic daughters larger than normal. Thus, HAM-1 regulates the position of the cleavage plane, apoptosis and mitotic potential in C. elegans asymmetric cell divisions.
当母细胞分裂产生两个不同的子细胞时,就会发生不对称细胞分裂,这一过程促进了后生动物细胞多样性的产生。在秀丽隐杆线虫的发育过程中,神经祖细胞的不对称分裂产生神经元、神经支持细胞和凋亡细胞。秀丽隐杆线虫的HAM-1是一种不对称分布的皮质蛋白,它调节其中一些不对称的神经母细胞分裂。在这里,我们表明HAM-1是一种新蛋白,并确定了对HAM-1功能以及向细胞皮质分布至关重要的残基。我们对ham-1突变体胚胎的表型分析表明,HAM-1仅控制产生凋亡细胞的神经母细胞分裂。此外,ham-1突变体胚胎含有许多异常大的细胞死亡尸体。对这种尸体表型的研究表明,它是由神经母细胞极性的逆转导致的。神经母细胞分裂平面的错位产生大小异常的子细胞,凋亡的子细胞比正常的大。因此,HAM-1在秀丽隐杆线虫的不对称细胞分裂中调节分裂平面的位置、凋亡和有丝分裂潜能。