Asymmetric cell division is an essential process in the development of diverse animals, including humans. Our stem cells must undergo repeated asymmetric cell disivions to produce ceils of critical importance to our health. The long-term objective of the proposed project is an understanding of how divide asymmetrically. We are using the nematode CaenorhabdiUs elegans as a model to study asymmetric cell division. Before the first cell division in C. elegans, P granules (ribonucleoprotein complexes that are essential for germline development) and several other proteins and mRNAs become asymmetrically localized to one end of the zygote or the other. Simultaneously, actin-based polarized flows of cortical and central cytoplasm occur. Later, during mitosis, the mitotic spindle moves to an asymmetric position. The result is unequal-sized daughter cells containing distinct molecular components. The potential for combining genetics with live imaging makes this system an excellent model for addressing questions about how cells divide asymmetrically.
Our specific aims are to (1) determine how known genes function in the localization of P granules, (2) investigate the mechanism of asymmetric mitotic spindle positioning in the C. elegans zygote, and (3) clone and characterize a new gene required for both P granule and mitotic spindle positioning. We expect that we will learn important new information about how cells divide asymmetrically that will suggest mechanisms and guide studies in mammals, including humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM068966-05
Application #
7224844
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Haynes, Susan R
Project Start
2003-05-01
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2009-04-30
Support Year
5
Fiscal Year
2007
Total Cost
$232,848
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
McCarthy Campbell, Erin K; Werts, Adam D; Goldstein, Bob (2009) A cell cycle timer for asymmetric spindle positioning. PLoS Biol 7:e1000088
Goldstein, Bob; Macara, Ian G (2007) The PAR proteins: fundamental players in animal cell polarization. Dev Cell 13:609-22
Marston, Daniel J; Goldstein, Bob (2006) Symmetry breaking in C. elegans: another gift from the sperm. Dev Cell 11:273-4
Goldstein, Bob; Takeshita, Hisako; Mizumoto, Kota et al. (2006) Wnt signals can function as positional cues in establishing cell polarity. Dev Cell 10:391-6
McCarthy, Erin K; Goldstein, Bob (2006) Asymmetric spindle positioning. Curr Opin Cell Biol 18:79-85
Lee, Jen-Yi; Marston, Daniel J; Walston, Timothy et al. (2006) Wnt/Frizzled signaling controls C. elegans gastrulation by activating actomyosin contractility. Curr Biol 16:1986-97
Marston, Daniel J; Goldstein, Bob (2006) Actin-based forces driving embryonic morphogenesis in Caenorhabditis elegans. Curr Opin Genet Dev 16:392-8
McCarthy, Erin K; Goldstein, Bob (2005) Asymmetric division: a kinesin for spindle positioning. Curr Biol 15:R591-3
Dudley, Nathaniel R; Goldstein, Bob (2005) RNA interference in Caenorhabditis elegans. Methods Mol Biol 309:29-38
Nance, Jeremy; Lee, Jen-Yi; Goldstein, Bob (2005) Gastrulation in C. elegans. WormBook :1-13

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