Han M, Aroian R V, Sternberg P W
Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena 91125.
Genetics. 1990 Dec;126(4):899-913. doi: 10.1093/genetics/126.4.899.
During induction of the Caenorhabditis elegans hermaphrodite vulva by the anchor cell of the gonad, six multipotent vulval precursor cells (VPCs) have two distinct fates: three VPCs generate the vulva and the other three VPCs generate nonspecialized hypodermis. Genes that control the fates of the VPCs in response to the anchor cell signal are defined by mutations that cause all six VPCs to generate vulval tissue (Multivulva or Muv) or that cause all six VPCs to generate hypodermis (Vulvaless or Vul). Seven dominant Vul mutations were isolated as dominant suppressors of a lin-15 Muv mutation. These mutations are dominant alleles of the gene let-60, previously identified only by recessive lethal mutations. Our genetic studies of these dominant Vul recessive lethal mutations, recessive lethal mutations, intragenic revertants of the dominant Vul mutations, and the closely mapping semi-dominant multivulva lin-34 mutations suggest that: (1) loss-of-function mutations of let-60 are recessive lethal at a larval stage, but they also cause a Vul phenotype if the lethality is rescued maternally by a lin-34 gain-of-function mutation. (2) The dominant Vul alleles of let-60 are dominant negative mutations whose gene products compete with wild-type activity. (3) lin-34 semidominant Muv alleles are either gain-of-function mutations of let-60 or gain-of-function mutations of an intimately related gene that elevates let-60 activity. We propose that let-60 activity controls VPC fates. In a wild-type animal, reception by a VPC of inductive signal activates let-60, and it generates into a vulval cell type; in absence of inductive signal, let-60 activity is low and the VPC generates hypodermal cells. Our genetic interaction studies suggest that let-60 acts downstream of let-23 and lin-15 and upstream of lin-1 and lin-12 in the genetic pathway specifying the switch between vulval and nonvulval cell types.
在秀丽隐杆线虫雌雄同体的阴门由性腺的锚定细胞诱导形成的过程中，六个多能性阴门前体细胞（VPC）有两种不同的命运：三个VPC形成阴门，另外三个VPC形成非特化的皮下组织。响应锚定细胞信号控制VPC命运的基因是由导致所有六个VPC都形成阴门组织（多阴门或Muv）或导致所有六个VPC都形成皮下组织（无阴门或Vul）的突变所定义的。七个显性Vul突变作为lin-15 Muv突变的显性抑制子被分离出来。这些突变是let-60基因的显性等位基因，该基因之前仅通过隐性致死突变被鉴定出来。我们对这些显性Vul隐性致死突变、隐性致死突变、显性Vul突变的基因内回复突变以及紧密连锁的半显性多阴门lin-34突变进行的遗传学研究表明：（1）let-60的功能丧失突变在幼虫阶段是隐性致死的，但如果通过lin-34的功能获得突变在母体中挽救了致死性，它们也会导致Vul表型。（2）let-60的显性Vul等位基因是显性负突变，其基因产物与野生型活性竞争。（3）lin-34半显性Muv等位基因要么是let-60的功能获得突变，要么是一个密切相关基因的功能获得突变，该基因会提高let-60的活性。我们提出let-60的活性控制VPC的命运。在野生型动物中，VPC接收诱导信号会激活let-60，使其分化为阴门细胞类型；在没有诱导信号的情况下，let-60的活性较低，VPC会产生皮下细胞。我们的遗传相互作用研究表明，在决定阴门和非阴门细胞类型之间转换的遗传途径中，let-60作用于let-23和lin-15的下游以及lin-1和lin-12的上游。
