Molecular genetics of maternally-controlled cell divisions

Abrams, Elliott W.; Fuentes, Ricardo; Marlow, Florence L.; Kobayashi, Manami; Zhang, Hong; Lu, Sumei; Kapp, Lee; Joseph, Shai R.; Kugath, Amy; Gupta, Tripti; Lemon, Virginia; Runke, Greg; Amodeo, Amanda A.; Vastenhouw, Nadine L.; Mullins, Mary C.


Author summary The earliest stages of animal development are regulated by factors in the egg that are made during oogenesis and are required for the embryo to develop prior to genome activation of the embryo itself. Because eggs are large, the cells of the early embryo are large and so unique mechanisms act during these stages of development. To study these molecular-genetic processes in a vertebrate, we have chemically induced mutations in the zebrafish germline and screened for mutant mothers (maternal-effect mutants) with defects in these processes. We identified three distinct classes of mutations affecting cell division in the early embryo. One of these mutations also exhibits a male-sterile phenotype. We identify the mutated genes in three of these mutants. We expect the remaining mutant lines will serve as important tools for elucidating molecular mechanisms involved in cell organization and/or positioning during the cleavage stage, as well as mechanisms critical for proper patterning of the early embryo. Forward genetic screens remain at the forefront of biology as an unbiased approach for discovering and elucidating gene function at the organismal and molecular level. Past mutagenesis screens targeting maternal-effect genes identified a broad spectrum of phenotypes ranging from defects in oocyte development to embryonic patterning. However, earlier vertebrate screens did not reach saturation, anticipated classes of phenotypes were not uncovered, and technological limitations made it difficult to pinpoint the causal gene. In this study, we performed a chemically-induced maternal-effect mutagenesis screen in zebrafish and identified eight distinct mutants specifically affecting the cleavage stage of development and one cleavage stage mutant that is also male sterile. The cleavage-stage phenotypes fell into three separate classes: developmental arrest proximal to the mid blastula transition (MBT), irregular cleavage, and cytokinesis mutants. We mapped each mutation to narrow genetic intervals and determined the molecular basis for two of the developmental arrest mutants, and a mutation causing male sterility and a maternal-effect mutant phenotype. One developmental arrest mutant gene encodes a maternal specific Stem Loop Binding Protein, which is required to maintain maternal histone levels. The other developmental arrest mutant encodes a maternal-specific subunit of the Minichromosome Maintenance Protein Complex, which is essential for maintaining normal chromosome integrity in the early blastomeres. Finally, we identify a hypomorphic allele of Polo-like kinase-1 (Plk-1), which results in a male sterile and maternal-effect phenotype. Collectively, these mutants expand our molecular-genetic understanding of the maternal regulation of early embryonic development in vertebrates.

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Título según WOS: Molecular genetics of maternally-controlled cell divisions
Título de la Revista: PLoS Genetics
Volumen: 16
Número: 4
Fecha de publicación: 2020


Notas: ISI