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

  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},
  volume={6 1},

The Spindle-Associated Microcephaly Protein, WDR62, Is Required for Neurogenesis and Development of the Hippocampus

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

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

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.

Disruptions in asymmetric centrosome inheritance and WDR62-Aurora kinase B interactions in primary microcephaly

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.

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-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice

It is revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes.

Wdr62 is involved in female meiotic initiation via activating JNK signaling and associated with POI in humans

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.

Downregulation of CDC25C in NPCs Disturbed Cortical Neurogenesis

The results indicate that Cdc25c plays an essential role in maintaining the proliferative state of NPCs during cortical development, and uncovers a novel role of CDC25C in NPC division and cell fate determination.



WDR62 is associated with the spindle pole and is mutated in human microcephaly

In human and mouse embryonic brain, it was found that WDR62 expression was restricted to neural precursors undergoing mitosis, lending support to the hypothesis that the exquisite control of the cleavage furrow orientation in mammalian neural precursor cell mitosis is critical both in causing MCPH when perturbed and, when modulated, generating the evolutionarily enlarged human brain.

Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture

A syndrome of congenital microcephaly and diverse defects in cerebral cortical architecture is described and important roles for WDR62, a WD40 repeat–containing protein expressed in neuronal precursors as well as in postmitotic neurons in the developing brain, are supported.

ASPM regulates Wnt signaling pathway activity in the developing brain.

It is demonstrated that knockdown of Aspm results in decreased Wnt-mediated transcription, and that expression of stabilized β-catenin can rescue this deficit.

Cdk5rap2 regulates centrosome function and chromosome segregation in neuronal progenitors

The findings suggest that the reduction in brain size observed in humans with mutations in CDK5RAP2 is associated with impaired centrosomal function and with changes in mitotic spindle orientation during progenitor proliferation.

Phosphorylation of SCG10/stathmin-2 determines multipolar stage exit and neuronal migration rate

It is found that JNK1 was highly active in developing cortex and that selective inhibition of JNK in the cytoplasm markedly increased both the frequency of exit from the multipolar stage and radial migration rate and ultimately led to an ill-defined cellular organization.

Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum

Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder.

The Suppression of CRMP2 Expression by Bone Morphogenetic Protein (BMP)-SMAD Gradient Signaling Controls Multiple Stages of Neuronal Development*

A novel mechanism that the BMP-SMAD signaling pathway controls neuronal migration and neurite outgrowth by suppressing the transcription of CRMP2 is revealed.

Aspm specifically maintains symmetric proliferative divisions of neuroepithelial cells

It is demonstrated that Aspm is crucial for maintaining a cleavage plane orientation that allows symmetric, proliferative divisions of NE cells during brain development, which also has implications for the evolution of mammalian brains.