Cell divisions must be correctly oriented, usually through mitotic spindle orientation, to ensure normal development. Extrinsic signals sometimes control division orientation, but how? To address this question, Adam Werts and co-workers have been investigating the localisation of the TPR-GoLoco protein pair GPR-1/2 in C. elegans embryos (see p. 4411). In four-cell stage embryos, GPR-1/2 is enriched at the junction between two cells – the endomesodermal precursor EMS and the germline precursor P2 – and both cells align their division towards this cell-cell contact. The researchers report that, unexpectedly, GPR-1/2 distribution is asymmetric in P2 but not in EMS. Instructive intercellular signalling through MES-1/SRC-1 determines the asymmetric localisation of GPR-1/2 in P2, they report, and this distribution (which is established through GPR-1/2 destabilisation at one cell contact, and its diffusion and stabilisation at another cell contact) is important for normal development. Overall, these results identify the dynamic localisation of GPR-1/2 as a key mediator of cell division orientation in response to external signalling.
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