Tags

Type your tag names separated by a space and hit enter

Molecular genetics of maternally-controlled cell divisions.
PLoS Genet. 2020 04; 16(4):e1008652.PG

Abstract

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.

Authors+Show Affiliations

Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America. Department of Biology, Purchase College, The State University of New York, Purchase, New York, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32267837

Citation

Abrams, Elliott W., et al. "Molecular Genetics of Maternally-controlled Cell Divisions." PLoS Genetics, vol. 16, no. 4, 2020, pp. e1008652.
Abrams EW, Fuentes R, Marlow FL, et al. Molecular genetics of maternally-controlled cell divisions. PLoS Genet. 2020;16(4):e1008652.
Abrams, E. W., Fuentes, R., Marlow, F. L., Kobayashi, M., Zhang, H., Lu, S., Kapp, L., Joseph, S. R., Kugath, A., Gupta, T., Lemon, V., Runke, G., Amodeo, A. A., Vastenhouw, N. L., & Mullins, M. C. (2020). Molecular genetics of maternally-controlled cell divisions. PLoS Genetics, 16(4), e1008652. https://doi.org/10.1371/journal.pgen.1008652
Abrams EW, et al. Molecular Genetics of Maternally-controlled Cell Divisions. PLoS Genet. 2020;16(4):e1008652. PubMed PMID: 32267837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular genetics of maternally-controlled cell divisions. AU - Abrams,Elliott W, AU - Fuentes,Ricardo, AU - Marlow,Florence L, AU - Kobayashi,Manami, AU - Zhang,Hong, AU - Lu,Sumei, AU - Kapp,Lee, AU - Joseph,Shai R, AU - Kugath,Amy, AU - Gupta,Tripti, AU - Lemon,Virginia, AU - Runke,Greg, AU - Amodeo,Amanda A, AU - Vastenhouw,Nadine L, AU - Mullins,Mary C, Y1 - 2020/04/08/ PY - 2019/07/08/received PY - 2020/02/04/accepted PY - 2020/04/23/revised PY - 2020/4/9/pubmed PY - 2020/7/21/medline PY - 2020/4/9/entrez SP - e1008652 EP - e1008652 JF - PLoS genetics JO - PLoS Genet. VL - 16 IS - 4 N2 - 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. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/32267837/Molecular_genetics_of_maternally-controlled_cell_divisions L2 - http://dx.plos.org/10.1371/journal.pgen.1008652 DB - PRIME DP - Unbound Medicine ER -