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Microcephaly-associated protein WDR62 regulates neurogenesis through JNK1 in the developing neocortex.

Authors: Xu, D  Zhang, F  Wang, Y  Sun, Y  Xu, Z 
Citation: Xu D, etal., Cell Rep. 2014 Jan 16;6(1):104-16. doi: 10.1016/j.celrep.2013.12.016. Epub 2014 Jan 2.
Pubmed: (View Article at PubMed) PMID:24388750
DOI: Full-text: DOI:10.1016/j.celrep.2013.12.016

Mutations of WD40-repeat protein 62 (WDR62) have been identified recently to cause human MCPH (autosomal-recessive primary microcephaly), a neurodevelopmental disorder characterized by decreased brain size. However, the underlying mechanism is unclear. Here, we investigate the function of WDR62 in brain development and the pathological role of WDR62 mutations. We find that WDR62 knockdown leads to premature differentiation of neural progenitor cells (NPCs). The defect can be rescued by wild-type human WDR62, but not by the five MCPH-associated WDR62 mutants. We demonstrate that WDR62 acts upstream of JNK signaling in the control of neurogenesis. Depletion of JNK1 and WDR62 incurs very similar defects including abnormal spindle formation and mitotic division of NPCs as well as premature NPC differentiation during cortical development. Thus, our findings indicate that WDR62 is required for proper neurogenesis via JNK1 and provide an insight into the molecular mechanisms underlying MCPH pathogenesis.

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RGD Object Information
RGD ID: 10047173
Created: 2015-07-11
Species: All species
Last Modified: 2015-07-11
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.