Forrester W C, Perens E, Zallen J A, Garriga G
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3204, USA.
Genetics. 1998 Jan;148(1):151-65. doi: 10.1093/genetics/148.1.151.
To understand the mechanisms that guide migrating cells, we have been studying the embryonic migrations of the C. elegans canal-associated neurons (CANs). Here, we describe two screens used to identify genes involved in CAN migration. First, we screened for mutants that died as clear larvae (Clr) or had withered tails (Wit), phenotypes displayed by animals lacking normal CAN function. Second, we screened directly for mutants with missing or misplaced CANs. We isolated and characterized 30 mutants that defined 14 genes necessary for CAN migration. We found that one of the genes, ceh-10, specifies CAN fate. ceh-10 had been defined molecularly as encoding a homeodomain protein expressed in the CANs. Mutations that reduce ceh-10 function result in Wit animals with CANs that are partially defective in their migrations. Mutations that eliminate ceh-10 function result in Clr animals with CANs that fail to migrate or express CEH-23, a CAN differentiation marker. Null mutants also fail to express CEH-10, suggesting that CEH-10 regulates its own expression. Finally, we found that ceh-10 is necessary for the differentiation of AIY and RMED, two additional cells that express CEH-10.
为了了解引导迁移细胞的机制，我们一直在研究秀丽隐杆线虫（C. elegans）中与排泄管相关的神经元（CANs）的胚胎迁移。在此，我们描述了用于鉴定参与CAN迁移的基因的两个筛选方法。首先，我们筛选了那些作为透明幼虫死亡（Clr）或尾部枯萎（Wit）的突变体，缺乏正常CAN功能的动物会表现出这些表型。其次，我们直接筛选了CAN缺失或位置异常的突变体。我们分离并鉴定了30个突变体，这些突变体定义了CAN迁移所需的14个基因。我们发现其中一个基因ceh-10决定了CAN的命运。ceh-10在分子水平上被定义为编码一种在CANs中表达的同源结构域蛋白。降低ceh-10功能的突变会导致出现Wit表型的动物，其CANs在迁移中存在部分缺陷。消除ceh-10功能的突变会导致出现Clr表型的动物，其CANs无法迁移或表达CAN分化标志物CEH-23。无效突变体也无法表达CEH-10，这表明CEH-10调节其自身的表达。最后，我们发现ceh-10对于另外两个表达CEH-10的细胞AIY和RMED的分化是必需的。
