A genetic and molecular analysis of spermiogenesis initiationin Caenorhabditis elegans
AuthorMuhlrad, Paul Jay
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PublisherThe University of Arizona.
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AbstractHow do cells acquire and regulate their specialized forms and functions? This is the fundamental question underlying the experiments described in this dissertation. To examine this question, I have peered deeply into an exquisitely specialized cell from a genetically tractable organism: the spermatozoon of the nematode, Caenorhabditis elegans. C. elegans sperm orchestrate a fantastic morphogenetic transformation under severe constraints of time and cellular resources. In response to an external signal, spermatids reorganize their membranes and cytoskeleton to form crawling spermatozoa. This maturation, termed spermiogenesis, ensues without any new gene expression. To better understand this signaling pathway, I isolated suppressors of a mutation in spe-27, another gene in the pathway. These suppressors are described in Chapters II and III. The suppressors bypass the requirement for spe-27 and three other genes in this pathway, spe-8, -12, and -29. Eighteen of the suppressors are new alleles of spe-6, a previously characterized gene required for an early stage of spermatogenesis. The original spe-6 alleles are loss-of-function mutations, which prevent Major Sperm Protein assembly into fibrous body-membranous organelles of spermatocytes, and arrest development in meiosis. I isolated the spe-6 gene, and found that it encodes a predicted protein-serine/threonine kinase, similar to casein kinase 1. The suppressors appear to be reduction-of-function mutations. I propose a model whereby SPE-6, along with its role in spermatocyte development, inhibits spermiogenesis until the activation signal is received. The signal is transduced through SPE-8, -12, -27, and -29 to relieve SPE-6 repression, triggering the formation of spermatozoa. Chapter IV describes continuing efforts to understand the spermiogenesis signaling pathway by identifying the spe-8 gene. To find spe-8 I exploited spermatogenesis-specific gene expression data obtained through microarray technology. SPE-8, like SPE-6, is a protein kinase, but of the non-receptor protein tyrosine kinase class. I identified mutations in all but one of the spe-8 mutants. Most are in the kinase domain; one is in an associated protein-binding (SH2) domain. Both SPE-6 and SPE-8 are members of large multigene families in C. elegans, many members of which appear to be spermatogenesis-specific or enriched. I discuss this and other ramifications of my research in Chapter V.
Degree ProgramGraduate College
Molecular and Cellular Biology