For the nematode Caenorhabditis elegans tail tip, a non-mitotic neural-epithelial tissue, differentiation occurs during the late larval switch to adulthood (L4) (Sulston and Horvitz, 1977; Sulston et al., 1980). In L4 hermaphrodites, the tail tip synthesizes an adult cuticle and exits the molting cycle; however, in males, the four tail tip epithelial cells (hyp8-11) undergo coordinated-tail tip morphogenesis (TTM) and migrate further anterior, resulting in a rounded posterior male tail (Nguyen et al., 1999). We have identified a novel gene that is required for tail tip terminal differentiation, lep-2/Makorin, which when lost, results in a temporal delay in the timely execution of male TTM and exit from the molting cycle in both C. elegans sexes. Using genetic analysis, we have determined lep-2 acts within the heterochronic regulatory network, downstream of lin-14 and upstream of lin-28. Makorins have diverse roles in eukaryotic development, including the regulation of cell division and differentiation in human stem cells, a feature shared with other conserved heterochronic genes (e.g. lin-4, lin-28, let-7 and lin-41) (Rougvie, 2001; Moss, 2007; Nimmo and Slack, 2009). This suggests that lep-2/Makorin regulates temporal development that ultimately synchronizes tissues for terminal differentiation to occur. And in L4, lep-2 is required for both TTM in males and the exit from the larval molting cycle in both sexes. We propose that the genetic regulation of developmental time is anciently conserved, synonymous with the regulation of stem cell differentiation and involves homologs of genes with "heterochronic" phenotypes in C. elegans, such as lep-2/Makorin.
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|Advisor:||Fitch, Dave H. A.|
|Commitee:||Albert Hubbard, E. Jane, Birnbaum, Kenneth, Christiaen, Lionel, Nance, Jeremy, Piano, Fabio|
|School:||New York University|
|School Location:||United States -- New York|
|Source:||DAI-B 74/07(E), Dissertation Abstracts International|
|Subjects:||Genetics, Evolution and Development, Developmental biology|
|Keywords:||Developmental timing, Epidermal, Evolution of sexual dimorphism, Mkrn, Morphogenesis, Temporal genetics|
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