We are interested in transcription factors that function in the regulation of cell fate determination during development. Our model system is the nematode C. elegans (a non-parasitic worm) that is widely used for developmental studies because of its small size, ease of culture in the laboratory, simple anatomy, rapid proliferation, and genetics. We are currently interested in several transcription factors that have been identified in other systems as important for mesoderm patterning and muscle formation. We have shown that the C. elegans MyoD and Twist transcription factors are important for the formation and patterning of post-embryonic mesodermal cells including muscle. By studying the phenotypes that result from mutations in these genes we are beginning to define their exact roles in regulating the development of specific subsets of muscle cells in C. elegans. As part of our efforts to understand cellular differentiation, we have characterized three genes that function in the G1 phase of the cell cycle. Cells must coordinate cell cycle exit with differentiation and G1 cell cycle factors are important for this process. We have shown that cyclin E is essential for all cell cycle during development whereas cyclin D functions only post-embryonically to regulate the cell cycle. This understanding of the basic cell cycle machinery in C. elegans allows us to put the action of transcription factors into developmental context. It also opens the way to manipulating cell cycle regulation to study the interactions between cell cycle regulation and differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK036117-11
Application #
6984516
Study Section
(LMB)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2004
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Fukushige, Tetsunari; Krause, Michael (2005) The myogenic potency of HLH-1 reveals wide-spread developmental plasticity in early C. elegans embryos. Development 132:1795-805
Hanover, John A; Forsythe, Michele E; Hennessey, Patrick T et al. (2005) A Caenorhabditis elegans model of insulin resistance: altered macronutrient storage and dauer formation in an OGT-1 knockout. Proc Natl Acad Sci U S A 102:11266-71
Brodigan, Thomas M; Liu, J i; Park, Morgan et al. (2003) Cyclin E expression during development in Caenorhabditis elegans. Dev Biol 254:102-15
Tonkin, Leath A; Saccomanno, Lisa; Morse, Daniel P et al. (2002) RNA editing by ADARs is important for normal behavior in Caenorhabditis elegans. EMBO J 21:6025-35
Corsi, Ann K; Brodigan, Thomas M; Jorgensen, Erik M et al. (2002) Characterization of a dominant negative C. elegans Twist mutant protein with implications for human Saethre-Chotzen syndrome. Development 129:2761-72
Berke, J D; Sgambato, V; Zhu, P P et al. (2001) Dopamine and glutamate induce distinct striatal splice forms of Ania-6, an RNA polymerase II-associated cyclin. Neuron 32:277-87
Kostrouchova, M; Krause, M; Kostrouch, Z et al. (2001) Nuclear hormone receptor CHR3 is a critical regulator of all four larval molts of the nematode Caenorhabditis elegans. Proc Natl Acad Sci U S A 98:7360-5
Cai, T; Krause, M W; Odenwald, W F et al. (2001) The IA-2 gene family: homologs in Caenorhabditis elegans, Drosophila and zebrafish. Diabetologia 44:81-8
Dichoso, D; Brodigan, T; Chwoe, K Y et al. (2000) The MADS-Box factor CeMEF2 is not essential for Caenorhabditis elegans myogenesis and development. Dev Biol 223:431-40
Corsi, A K; Kostas, S A; Fire, A et al. (2000) Caenorhabditis elegans twist plays an essential role in non-striated muscle development. Development 127:2041-51

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