The stem cells of neurogenesis and carcinogenesis share many properties, including proliferative rate, an extensive replicative potential, the potential to generate different cell types of a given tissue, and an ability to independently migrate to a damaged area. This is also evidenced by the common molecular principles regulating key processes associated with cell division and apoptosis. Autosomal recessive primary microcephaly (MCPH) is a neurogenic mitotic disorder that is characterized by decreased brain size and mental retardation. Until now, a total of 25 genes have been identified that are known to be associated with MCPH. The inactivation (yin) of most MCPH genes leads to neurogenesis defects, while the upregulation (yang) of some MCPH genes is associated with different kinds of carcinogenesis. Here, we try to summarize the roles of MCPH genes in these two diseases and explore the underlying mechanisms, which will help us to explore new, attractive approaches to targeting tumor cells that are resistant to the current therapies.

The c-Jun N-terminal kinase (JNK) is highly evolutionarily conserved and plays important roles in a broad range of physiological and pathological processes. The WD40-repeat protein 62 (WDR62) is a scaffold protein that recruits different components of the JNK signaling pathway to regulate several human diseases including neurological disorders, infertility, and tumorigenesis. Recent studies revealed that WDR62 regulates the process of neural stem cell mitosis and germ cell meiosis through JNK signaling. In this review we summarize the roles of WDR62 and JNK signaling in neuronal and non-neuronal contexts and discuss how JNK-dependent signaling regulates both processes. WDR62 is involved in various human disorders via JNK signaling regulation, and may represent a promising therapeutic strategy for the treatment of related diseases.

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Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we 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. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.