GENETIC CONTROL OF NEMATODE DEVELOPMENT

秀丽隐杆线虫的发育涉及一个 细胞不变且精确已知的时间模式或序列 分裂和分化事件。 这项工作的长期目标是 为了阐明这种时间发展进程是如何在基因上 编码. 要解决的一般问题是：1）角色是什么 个体基因在控制发育的时间序列中的作用 事件？ 2)这些基因的组织特异性和阶段特异性是什么？ 3)编码细胞外基因与 细胞内在的功能，在阐述和解释时间 在开发过程中，？ 4)这些基因是如何在 它们自身以及控制基本细胞过程的基因， 分化与分化？ 的遗传和表型特性 具有改变的发育时间模式的突变体（“异时的 突变体”）将进行详细研究。 我们将试图找出 通过突变，所有参与控制特定时间开关的基因， 细胞命运-从幼虫程序（细胞分裂和幼虫 角质层合成）到成人程序（成人角质层合成） 皮下“缝”细胞。 对于每个新发现的基因， 在之前发现的影响这一开关的五个基因中， 将应用遗传分析来确定它们各自的零 表型，因此它们的野生型发育作用。 功能 将通过构建多突变菌株来探索相互作用， 两个或多个异时基因中已知的遗传病变。 温度 使用温度敏感等位基因的移位实验将用于 研究每个基因作用时间。 将采用镶嵌分析 以确定它们是否在细胞中自主发挥作用。 这项工作 使用线虫作为模型系统来研究有关 细胞分裂、分化和模式形成的遗传控制 因此，这可能有助于加深我们对遗传病原因的理解。 发育障碍和肿瘤形成。

The development of the small nematode Caenorhabditis elegans involves an invariant and precisely known temporal pattern or sequence of cell divisions and differentiation events. The long term goal of this work is to elucidate how this temporal schedule of development is genetically encoded. The general questions to be addressed are: 1) What are the roles of individual genes in controlling temporal sequences of developmental events? 2) What are the tissue- and stage-specificities of those genes? 3) What are the relative roles of genes encoding cell-extrinsic vs cell-intrinsic functions in elaborating and interpreting temporal information during development? 4) How do these genes interact among themselves and with genes controlling basic cellular processes such as cell division and differentiation? The genetic and phenotypic properties of mutants with altered temporal patterns of development ("heterochronic mutants") will be studied in detail. An attempt will be made to identify by mutation all genes involved in controlling a specific temporal switch in cell fate - the switch from larval programs (cell division and larval cuticle synthesis) to adult programs (adult cuticle synthesis) for hypodermal "seam" cells. For each newly identified gene, and for certain of the five previously identified genes affecting this switch, detailed genetic analysis will be applied to determine their respective null phenotypes and thus their wild-type developmental roles. Functional interactions will be explored by constructing multiply-mutant strains with known genetic lesions in two or more heterochronic genes. Temperature shift experiments using temperature-sensitive alleles will be used to investigate time of action of each gene. Mosaic analysis will be employed for selected genes to determine if they act cell autonomously. This work uses the nematode as a model system to study basic questions concerning the genetic control of cell divisions, differentiation and pattern formation and therefore may help deepen our understanding of the causes of genetic developmental disorders and neoplasia.