No abstract

Though the adult central nervous system has been considered a comparatively static tissue with little turnover, it is well established today that new neural cells are generated throughout life. Neural stem/progenitor cells (NS/ PCs) can self-renew and generate all types of neural cells. The proliferation of NS/PCs, and differentiation and fate determination of PCs are regulated by extrinsic factors such as growth factors, neurotrophins, and morphogens. Although several extrinsic factors that influence neurogenesis have already been reported, little is known about the role of soluble molecules in neural niche regulation. In this review, we will introduce the soluble molecule Akhirin and discuss its role in the eye and spinal cord during development.

Summary 23The chromatin remodeling gene CHD8 represents a central node in early neurodevelopmental 24 gene networks implicated in autism. We examined the impact of heterozygous germline Chd8 25 mutation on neurodevelopment in mice. Network analysis of neurodevelopmental gene 26 expression revealed subtle yet strongly significant widespread transcriptional changes in Chd8 +/-27 mice across autism-relevant networks from neurogenesis to synapse function. Chd8 +/-expression 28 signatures included enrichment of RNA processing genes and a Chd8-regulated module featuring 29 altered transcription of chromatin remodeling, splicing, and cell cycle genes. Chd8 +/-mice 30 exhibited increased proliferation during brain development and neonatal increase in cortical 31 length and volume. Structural MRI confirmed regional brain volume increase in adult Chd8 +/-32 mice, consistent with clinical macrocephaly. Adult Chd8 +/-mice displayed normal social 33 interactions, and repetitive behaviors were not evident. Our results show that Chd8 +/-mice 34 exhibit neurodevelopmental changes paralleling CHD8 +/-humans and show that Chd8 is a global 35 genomic regulator of pathways disrupted in neurodevelopmental disorders.