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

@article{Xu2014MicrocephalyassociatedPW,
  title={Microcephaly-associated protein WDR62 regulates neurogenesis through JNK1 in the developing neocortex.},
  author={Dan Xu and Feng Zhang and Yaqing Wang and Yiming Sun and Zhiheng Xu},
  journal={Cell reports},
  year={2014},
  volume={6 1},
  pages={
          104-16
        }
}
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… 
The Spindle-Associated Microcephaly Protein, WDR62, Is Required for Neurogenesis and Development of the Hippocampus
TLDR
Findings reveal that WDR62 is required for neurogenesis and the growth of the hippocampus during embryonic development and resulted in a significant reduction in the thickness of the hippocampal ventricular zone and the area of the dentate gyrus.
MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis
TLDR
The findings demonstrate that the coordinated reciprocal and bidirectional regulation among MEKK3, FBW7, WDR62, and JNK1, is required for fine-tuned JNK signaling for the control of balanced NPC self-renewal and differentiation during cortical development.
SRPS associated protein WDR60 regulates the multipolar-to-bipolar transition of migrating neurons during cortical development
TLDR
It is reported that WDR60 is essential for embryonic development and plays a critical role in the multipolar-bipolar transition and migration of newborn neurons during brain development and the pathogenesis of Wdr60 deficiency associated with SRPS.
Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth
TLDR
Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged and glial lineage-specific WDR 62 depletion significantly decreased brain volume, which was further decreased by W DR62 co-depletion.
Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly
TLDR
These findings demonstrate critical and diverse functions of WDR62 in neocortical development and provide insight into the mechanisms by which its disruption leads to a plethora of structural abnormalities.
The association of microcephaly protein WDR62 with CPAP/IFT88 is required for cilia formation and neocortical development.
TLDR
It is found that WDR62 mutant proteins (V66M and R439H) localize to the basal body but fail to recruit CPAP, a protein that is required for cilia formation, which underpins the maintenance of radial glia and implicates ciliary dysfunction as underlying the pathology of MCPH2 patients.
Wdr62 is involved in female meiotic initiation via activating JNK signaling and associated with POI in humans
TLDR
It is reported that the Wdr62 (WD40-repeat protein 62) is involved in meiotic initiation as a permissive factor rather than an instructive factor, and mutation of WDR62 is one of the potential etiologies of POI in humans.
Molecular evolution of WDR62, a gene that regulates neocorticogenesis
TLDR
Comparative analysis of human WDR62 with two archaic humans and modern human populations revealed that five hominin specific amino acid residues might have been accumulated in the common ancestor of extinct archaic human and modern humans about 550,000–765,000 years ago and suggests that the ability of WDR 62 protein to mediate the neurogenesis has been altered in the course of hominIn evolution.
The Microcephaly-Associated Protein Wdr62/CG7337 Is Required to Maintain Centrosome Asymmetry in Drosophila Neuroblasts.
TLDR
It is proposed that CG7337/Wdr62, a microtubule-associated protein, is required for the maintenance of interphase microtubules, thereby regulating centrosomal Polo and Plp levels.
Opposing roles for JNK and Aurora A in regulating the association of WDR62 with spindle microtubules
TLDR
It is demonstrated that the WD40-repeat region of WDR62 is required for microtubule association, whereas the disordered C-terminal region regulates cell-cycle-dependent compartmentalization, with opposing roles for JNK and AURKA in determining its spindle association.
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