XB-ART-51304Nat Commun. June 23, 2015; 6 8386.
miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways.
Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.
PubMed ID: 26381333
PMC ID: PMC4595761
Article link: Nat Commun.
Genes referenced: arhgap1 gnl3 igf2bp3 mcc mut notch1 odc1 rho rho.2 rhoa rras tub
Morpholinos referenced: dll1 miR-449 protector MO1 dll1 miR-449 protector MO2 miR-449 MO1 miR-449 MO2 miR-449 MO3 rras MO1 rras miR-449 protector MO
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