Cytokinesis, the physical process that divides daughter cells, is of critical importance to development and growth regulation. In many instances, cytokinesis is coupled with the asymmetric segregation of cellular determinants, which in turn results in the functional diversification of cell types. A basic question in biology is to understand the molecular mechanisms underlying the segregation of cell fate determinants, in particular the germ plasm, a specialized cytoplasm that confers the germ cell fate. Systematic screens for maternal-effect mutations in the zebrafish, Danio rerio, have identified genes that affect the processes of cytokinesis and germ plasm segregation, which in this organism are intimately linked. To our knowledge, these are the first identified mutations in vertebrate genes required for cytokinesis. This proposal focuses on the analysis of the function of one of these genes, Cellular Island, which we show codes for Aurora B kinase, a chromosomal passenger protein involved in furrow initiation. Functional analysis of this gene suggests that it has an essential role in furrow formation in lateral, but not medial, regions of the embryonic blastodisc. We will test the hypothesis that furrow-inducing signals from different microtubule-based structures, possibly through the action of distinct downstream mediators such as Aurora B kinase, are required for cytokinesis in separate regions of the blastodisc. The proposed research will also determine the precise roles of these signals in the process of germ plasm recruitment to the forming furrow. The understanding of these mechanisms will provide insights on both a fundamental cellular process (cytokinesis) and a fundamental developmental process (germ plasm segregation), and the functional relationship between them in the early vertebrate embryo. The proposed research addresses fundamental mechanisms of cell division and the determination of cell fate, in particular, the specification of the germ cells. Knowledge acquired through these studies will lead to progress in therapies that alleviate health problems related to reproductive biology, cancer, and stem cell and tissue development.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM065303-09
Application #
8101258
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Haynes, Susan R
Project Start
2002-03-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
9
Fiscal Year
2011
Total Cost
$272,922
Indirect Cost
Name
University of Wisconsin Madison
Department
Genetics
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Welch, Elaine L; Eno, Celeste C; Nair, Sreelaja et al. (2017) Functional Manipulation of Maternal Gene Products Using In Vitro Oocyte Maturation in Zebrafish. J Vis Exp :
Hasley, Andrew; Chavez, Shawn; Danilchik, Michael et al. (2017) Vertebrate Embryonic Cleavage Pattern Determination. Adv Exp Med Biol 953:117-171
Pelegri, F; Mullins, M C (2016) Genetic screens for mutations affecting adult traits and parental-effect genes. Methods Cell Biol 135:39-87
Zampedri, Cecilia; Tinoco-Cuellar, Maryana; Carrillo-Rosas, Samantha et al. (2016) Zebrafish P54 RNA helicases are cytoplasmic granule residents that are required for development and stress resilience. Biol Open 5:1473-1484
Eno, Celeste; Solanki, Bharti; Pelegri, Francisco (2016) aura (mid1ip1l) regulates the cytoskeleton at the zebrafish egg-to-embryo transition. Development 143:1585-99
Baars, Destiny L; Takle, Kendra A; Heier, Jonathon et al. (2016) Ploidy Manipulation of Zebrafish Embryos with Heat Shock 2 Treatment. J Vis Exp :
Ge, Xiaoyan; Grotjahn, Danielle; Welch, Elaine et al. (2014) Hecate/Grip2a acts to reorganize the cytoskeleton in the symmetry-breaking event of embryonic axis induction. PLoS Genet 10:e1004422
Welch, Elaine; Pelegri, Francisco (2014) Cortical depth and differential transport of vegetally localized dorsal and germ line determinants in the zebrafish embryo. Bioarchitecture 5:13-26
Nair, Sreelaja; Lindeman, Robin E; Pelegri, Francisco (2013) In vitro oocyte culture-based manipulation of zebrafish maternal genes. Dev Dyn 242:44-52
Nair, Sreelaja; Marlow, Florence; Abrams, Elliott et al. (2013) The chromosomal passenger protein birc5b organizes microfilaments and germ plasm in the zebrafish embryo. PLoS Genet 9:e1003448

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