Asymmetric cell divisions generate cell diversity during development, and the orientation of the axis of these divisions determines the future position of differentiated cells. But is the asymmetrical localization of the polarity (PAR) proteins that control asymmetric cell division regulated by extracellular or intracellular signals? On p. 3337, Yukinobu Arata and colleagues answer this controversial question. In C. elegans embryos, the P0 zygote and the P1, P2 and P3 germline cells undergo a series of asymmetric divisions. By examining the development of these germline cells in vitro, the researchers show that, although PAR-2 is distributed asymmetrically in P2 and P3 cells in the absence of extracellular signals, the orientation of PAR-2 localization in these cells depends on their contact with endodermal precursor cells. Other experiments indicate that the endodermal precursor cells control the orientation of PAR-2 localization by extracellular signalling via the MES1/SRC1 pathway. The researchers propose, therefore, that Src is an evolutionarily conserved molecular link that coordinates extrinsic cues with PAR protein localization during asymmetric cell divisions.
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