Cytokinesis, the physical process that divides daughter cells, is of fundamental 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. During the systematic identification of maternal-effect mutations in the zebrafish, two mutations, in the genes aura and nebel, were identified which affect both of these processes. Mutations in these genes result in embryonic lethality due to defects in cell adhesion and membrane deposition. In both cases, the basis of this phenotype is a defect in the completion of cytokinesis, possibly in the addition or stabilization of new membrane at the cleavage plane. In addition, both of these mutations affect different steps in a pathway of segregation of the vasa RNA, a component of a specialized cytoplasm that confers the germ cell fate. Both types of defects may be based on the inability of the cytoskeleton to undergo specific rearrangements required for its function: aura-dependent microfilament rearrangements at multiple stages during early cleavage and nebel-dependent microtubule reorganization at the forming furrow. The proposed research will determine the precise roles of these genes in the process of cytokinesis and the segregation of the vasa RNA. For this purpose we will use cell biological techniques to visualize cellular components in wild-type and mutant embryos and inhibitor studies to determine the role of subcellular processes or networks. In addition, we will determine the molecular identity of the affected genes through a positional cloning approach. The understanding of these processes will provide insights on a variety of poorly understood subjects: i) the processes involved in the completion of cytokinesis, ii) the asymmetric segregation of RNA and other products within dividing cells, and iii) the functional relationship between the cellular mechanisms required for these two processes.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Reproductive Biology Study Section (REB)
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Haynes, Susan R
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University of Wisconsin Madison
Schools of Earth Sciences/Natur
United States
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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; 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
Eno, Celeste; Pelegri, Francisco (2013) Gradual recruitment and selective clearing generate germ plasm aggregates in the zebrafish embryo. Bioarchitecture 3:125-32

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