We use the nematode Caenorhabditis elegans as a model system for studying the molecular mechanisms by which developmental determinants specify the different fates of early embryonic cells (blastomeres). We have shown that the maternally expressed C. elegans gene skn-1 is required to specify the fate of a 4-cell stage blastomere called EMS. The ventrally-positioned EMS blastomere produces many different cell fates, contributing to both mesodermal and endodermal tissues. In skn-1 mutant embryos, EMS instead adopts a fate more like that of its sister blastomere in the 4-cell stage embryo. Genetic and molecular analyses suggest that skn-1 may encode an early embryonic determinant that acts by regulating the transcription of zygotic genes in descendants if EMS, and that other maternal genes restrict skn-1(+) activity to only the EMS blastomere. We propose experiments designed to address three fundamental issues concerning the regulation and function of skn1 as a developmental determinant in the early C. elegans embryo. (1) How is the expression of maternal skn-1 mRNA regulated such that high levels of Skn-1 protein accumulate only in a subset of early blastomeres? (2) What other maternally expressed genes are required for the EMS blastomere to produce its proper pattern of cell fates? (3) What zygotically expressed genes are targets of skn-1 transcriptional regulation in an EMS pathway of blastomere development? Our goal is to use skn-1 as an entry point for defining the steps in a genetic pathway that controls blastomere fate. We think this information will be interesting particularly in comparison to the much more detailed understanding we currently have of early embryogenesis in the fruit fly, Drosophila melanogaster. In Drosophila, the fate map of the embryo is largely determined during a time in which all embryonic nuclei share a common syncytial cytoplasm, before cell membranes partition the embryo into cellular compartments. In contrast, C. elegans embryos are completely cellularized during development. Studies of blastomere fate specification, in embryos that have their nuclei partitioned by cell membranes, will contribute to our general understanding of how different animal body plans develop and evolve.

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Molecular Cytology Study Section (CTY)
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University of Oregon
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Sugioka, Kenji; Fielmich, Lars-Eric; Mizumoto, Kota et al. (2018) Tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans asymmetric cell division. Proc Natl Acad Sci U S A 115:E954-E963
Sugioka, Kenji; Bowerman, Bruce (2018) Combinatorial Contact Cues Specify Cell Division Orientation by Directing Cortical Myosin Flows. Dev Cell 46:257-270.e5
Mok, Calvin A; Au, Vinci; Thompson, Owen A et al. (2017) MIP-MAP: High-Throughput Mapping of Caenorhabditis elegans Temperature-Sensitive Mutants via Molecular Inversion Probes. Genetics 207:447-463
Sugioka, Kenji; Hamill, Danielle R; Lowry, Joshua B et al. (2017) Centriolar SAS-7 acts upstream of SPD-2 to regulate centriole assembly and pericentriolar material formation. Elife 6:
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Connolly, Amy A; Sugioka, Kenji; Chuang, Chien-Hui et al. (2015) KLP-7 acts through the Ndc80 complex to limit pole number in C. elegans oocyte meiotic spindle assembly. J Cell Biol 210:917-32
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