Abstract
Embryogenesis depends on a tightly regulated balance between mitosis, differentiation, and morphogenesis. Understanding how the embryo uses a relatively small number of proteins to transition between growth and morphogenesis is a central question of developmental biology, but the mechanisms controlling mitosis and differentiation are considered to be fundamentally distinct. Here we show the mitotic kinase Polo, which regulates all steps of mitosis in Drosophila, also directs cellular morphogenesis after cell cycle exit. In mitotic cells, the Aurora kinases activate Polo to control a cytoskeletal regulatory module that directs cytokinesis. We show that in the post-mitotic mesoderm, the control of Polo activity transitions from the Aurora kinases to the uncharacterized kinase Back Seat Driver (Bsd), where Bsd and Polo cooperate to regulate muscle morphogenesis. Polo and its effectors therefore direct mitosis and cellular morphogenesis, but the transition from growth to morphogenesis is determined by the spatiotemporal expression of upstream activating kinases.
Highlights
Embryogenesis depends on a tightly regulated balance between mitosis, differentiation, and morphogenesis
During mitotic entry, activating phosphorylation of the kinase domain (KD) by Aurora B (AurB) relieves Polo-Box Domain (PBD) binding to Map[205] and promotes PBD binding to pro-mitotic substrates and structures[16,17,18]
The allele recovered from our screen is an embryonic lethal nonsense mutation (Q545*) that is predicted to produce a C-terminal truncation (Fig. 1c). bsd encodes a conserved serine/threonine kinase orthologous to the vacciniarelated kinases (VRKs), and proteins in the VRK family contain a single conserved kinase domain (KD) near the N-terminus, and a highly variable C-terminus (Fig. 1c and Supplementary Fig. 1C, D)
Summary
Embryogenesis depends on a tightly regulated balance between mitosis, differentiation, and morphogenesis. We show the mitotic kinase Polo, which regulates all steps of mitosis in Drosophila, directs cellular morphogenesis after cell cycle exit. The Aurora kinases activate Polo to control a cytoskeletal regulatory module that directs cytokinesis. We show that in the post-mitotic mesoderm, the control of Polo activity transitions from the Aurora kinases to the uncharacterized kinase Back Seat Driver (Bsd), where Bsd and Polo cooperate to regulate muscle morphogenesis. The transition from mitosis to cellular morphogenesis is achieved through the spatially and temporally restricted expression of the Aurora kinases and Bsd. The Polo orthologue Plk[1] was activated by the Bsd orthologue Vrk[3] in mammalian cells, arguing Bsd regulates a conserved intracellular signaling pathway that directs muscle morphogenesis
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