Novel heterochronic functions of the Caenorhabditis elegans period-related protein LIN-42.
Novel heterochronic functions of the Caenorhabditis elegans period-related protein LIN-42.
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DOI：
10.1016/j.ydbio.2005.09.044
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发表时间：
2006
影响因子：
2.7
通讯作者：
Jason M Tennessen;Heather F. Gardner;M. Volk;A. Rougvie
中科院分区：
文献类型：
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作者：
Jason M Tennessen;Heather F. Gardner;M. Volk;A. Rougvie
LIN-42是秀丽隐杆线虫周期（Per）昼夜节律蛋白家族的同源物，作为异慢性途径的成员，调节时间细胞身份。我们证明lin-42的作用很广泛，在性腺、外阴和性肌母细胞的发育事件中，除了在皮下末梢分化的时序上有明确的作用外。在外阴、性肌母细胞和皮下组织中，lin-42的活性可防止过早发生特定阶段的细胞分裂模式。大多数异慢性基因都具有这种与阶段相适应的细胞分裂模式的一般功能；它们的突变暂时改变了特定阶段的分裂模式。相比之下，在已知的异慢性基因中，lin-42在性腺形态发生的定时功能是独一无二的：lin-42的失活导致性腺臂过早反射，这种表型暗示lin-42在细胞迁移的时间调节中起作用。lin-42的另外三个同工异构体被鉴定出来，扩展了我们对lin-42位点的看法，并显著扩展了lin-42与其他PER家族成员之间的同源性。我们发现，LIN-42与PER蛋白相似，具有动态表达模式；在胚胎后发育过程中，它的水平相对于蜕皮而波动。转化救援研究表明lin-42在功能上是两面性的。有趣的是，在转基因动物中，标志性的PAS结构域对于LIN-42的功能是必不可少的。
LIN-42, the Caenorhabditis elegans homolog of the Period (Per) family of circadian rhythm proteins, functions as a member of the heterochronic pathway, regulating temporal cell identities. We demonstrate that lin-42 acts broadly, timing developmental events in the gonad, vulva, and sex myoblasts, in addition to its well-established role in timing terminal differentiation of the hypodermis. In the vulva, sex myoblasts, and hypodermis, lin-42 activity prevents stage-specific cell division patterns from occurring too early. This general function of timing stage-appropriate cell division patterns is shared by the majority of heterochronic genes; their mutation temporally alters stage-specific division patterns. In contrast, lin-42 function in timing gonad morphogenesis is unique among the known heterochronic genes: inactivation of lin-42 causes the elongating gonad arms to reflex too early, a phenotype which implicates lin-42 in temporal regulation of cell migration. Three additional isoforms of lin-42 are identified that expand our view of the lin-42 locus and significantly extend the homology between LIN-42 and other PER family members. We show that, similar to PER proteins, LIN-42 has a dynamic expression pattern; its levels oscillate relative to the molts during postembryonic development. Transformation rescue studies indicate lin-42 is bipartite with respect to function. Intriguingly, the hallmark PAS domain is dispensable for LIN-42 function in transgenic animals.