|ZFIN ID: ZDB-PUB-160527-4|
miR-219 regulates neural progenitors by dampening apical Par protein-dependent Hedgehog signaling
Hudish, L.I., Galati, D.F., Ravanelli, A.M., Pearson, C.G., Huang, P., Appel, B.
|Source:||Development (Cambridge, England) 143(13): 2292-304 (Journal)|
|Registered Authors:||Appel, Bruce, Huang, Peng, Ravanelli, Andrew M.|
|Keywords:||MicroRNA, Polarity, Hedgehog, Neural progenitors, Zebrafish|
|PubMed:||27226318 Full text @ Development|
Hudish, L.I., Galati, D.F., Ravanelli, A.M., Pearson, C.G., Huang, P., Appel, B. (2016) miR-219 regulates neural progenitors by dampening apical Par protein-dependent Hedgehog signaling. Development (Cambridge, England). 143(13):2292-304.
ABSTRACTThe transition of dividing neuroepithelial progenitors to differentiated neurons and glia is essential to the formation of a functional nervous system. Sonic Hedgehog (Shh) is a mitogen for spinal cord progenitors, but how cells become insensitive to the proliferative effects of Shh is not well understood. Because Shh reception occurs at primary cilia, which are positioned within the apical membrane of neuroepithelial progenitors, we hypothesized that loss of apical characteristics reduces Shh signaling response, causing cell cycle exit and differentiation. We tested this hypothesis using genetic and pharmacological manipulation, gene expression analysis and time-lapse imaging of zebrafish embryos. Blocking function of miR-219, a microRNA that down regulates apical Par polarity proteins and promotes progenitor differentiation, elevated Shh signaling. Inhibition of Shh signaling reversed the effects of miR-219 depletion and forced expression of Shh phenocopied miR-219 deficiency. Time-lapse imaging revealed that knockdown of miR-219 function accelerated the growth of primary cilia, revealing a possible mechanistic link between miR-219-mediated regulation of apical Par proteins and Shh signaling. Thus, miR-219 appears to decrease progenitor sensitivity to Shh signaling, thereby driving them toward differentiation.