Drosophila Embryonic Cell-Cycle Mutants

Abstract

Nearly all cell division mutants in Drosophila were recovered in late larval/pupal lethal screens, with less than 10 embryonic lethal mutants identified, because larval development occurs without a requirement for cell division. Only cells in the nervous system and the imaginal cells that generate the adult body divide during larval stages, with larval tissues growing by increasing ploidy rather than cell number. Thus, most mutants perturbing mitosis or the cell cycle do not manifest a phenotype until the adult body differentiates in late larval and pupal stages. To identify cell-cycle components whose maternal pools are depleted in embryogenesis or that have specific functions in embryogenesis, we screened for mutants defective in cell division during embryogenesis. Five new alleles of Cyclin E were recovered, ranging from a missense mutation that is viable to stop codons causing embryonic lethality. These permitted us to investigate the requirements for Cyclin E function in neuroblast cell fate determination, a role previously shown for a null Cyclin E allele. The mutations causing truncation of the protein affect cell fate of the NB6-4 neuroblast, whereas the weak missense mutation has no effect. We identified mutations in the pavarotti (pav) and tumbleweed (tum) genes needed for cytokinesis by a phenotype of large and multinucleate cells in the embryonic epidermis and nervous system. Other mutations affecting the centromere protein CAL1 and the kinetochore protein Spc105R caused mitotic defects in the nervous system.

Progressive loss of RacGAP1/ ogre activity has sequential effects on cytokinesis and zebrafish development

“…Loss of function mutations in the homologs of racgap1 or mklp1 in Drosophila and C. elegans are embryonic lethal when homozygous (Adams et al, 1998;Jantsch-Plunger et al, 2000;Powers et al, 1998;Somers and Saint, 2003;Unhavaithaya et al, 2013;Zavortink et al, 2005). However, while the cytokinesis defect has been much studied in these mutants the cause of lethality has been largely ignored perhaps because perturbations in cytokinesis are apparent well before cells start to die.…”

“…Because loss of function mutations in nematodes and fruit flies are embryonic lethals (Jantsch-Plunger et al, 2000;Jones and Bejsovec, 2005;Unhavaithaya et al, 2013;Zavortink et al, 2005), less is known about other roles RacGAP1 may have. Nevertheless, there is evidence that during polarization of the arcade cell epithelium in C. elegans, myotube extension and neurite outgrowth in Drosophila as well as neural migration in mammals, RacGAP1 (together with MKLP1) may have organizing properties of the cytoskeletal machinery (del Castillo et al, 2015;Falnikar et al, 2013;Guerin and Kramer, 2009;Lores et al, 2014;Portereiko et al, 2004).…”

Centromere proteins CENP-C and CAL1 functionally interact in meiosis for centromere clustering, pairing, and chromosome segregation

“…S1 C and D). This allele was used in combination with homozygous lethal alleles of cenp-C and cal1 we recovered from a screen for mutants with mitotic defects during Drosophila embryogenesis (30). These mutations cause C-terminal truncations in the proteins (Fig.…”