The migratory path of DTCs determines the shape of the C. elegans gonad. How the spatiotemporal migration pattern is regulated is not clear. We identified a conserved transcription factor BLMP-1 as a central component of a gene regulatory circuit required for the spatiotemporal control of DTC migration. BLMP-1 levels regulate the timing of the DTC dorsal turn, as high levels delay the turn and low levels result in an early turn. We identify and characterize upstream regulators that control BLMP-1 levels. These regulators function in two ways, i.e. by destabilization of BLMP-1 through ubiquitin-mediated proteolysis and by transcriptional repression of the blmp-1 gene to down-regulate BLMP-1. Interestingly, blmp-1 also negatively controls these regulators. Our data suggest that a dietary signal input acts together with a double-negative feedback loop to switch DTCs from the “blmp-1-on” to the “blmp-1-off” state, promoting their dorsal turn. Furthermore, we show that some protein interactions in the circuit are conserved in C. elegans and humans. Our work defines a novel function of the conserved blmp-1 gene in the temporal control of cell migration, and establishes a gene regulatory circuit that integrates the temporal and spatial inputs to direct cell migration during organogenesis.
Vyšlo v časopise: BLMP-1/Blimp-1 Regulates the Spatiotemporal Cell Migration Pattern in. PLoS Genet 10(6): e32767. doi:10.1371/journal.pgen.1004428 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004428
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