Co-culture system of human skin equivalents with mouse neural spheroids.

This study describes a co-culture system of human skin equivalents (HSEs) and dorsal root ganglion (DRG) neurons. We prepared spheroids of mouse DRG neurons with or without Schwann cells (SCs). Spheroids comprising DRG neurons and SCs showed longer neurite extensions than those comprising DRG neurons alone.

Subcellular mRNA localization and local translation of Arhgap11a in radial glial progenitors regulates cortical development.

mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in polarized, elongated cells. These features are especially prominent in radial glial cells (RGCs), which are neural and glial precursors of the developing cerebral cortex and scaffolds for migrating neurons. Yet the mechanisms by which subcellular RGC compartments accomplish their diverse functions are poorly understood.

CROCCP2 acts as a human-specific modifier of cilia dynamics and mTOR signaling to promote expansion of cortical progenitors.

The primary cilium is a central signaling component during embryonic development. Here we focus on CROCCP2, a hominid-specific gene duplicate from ciliary rootlet coiled coil (CROCC), also known as rootletin, that encodes the major component of the ciliary rootlet. We find that CROCCP2 is highly expressed in the human fetal brain and not in other primate species.

The tyrosine capsid mutations on retrograde adeno-associated virus accelerates gene transduction efficiency.

Adeno-associated virus (AAV) vector is a critical tool for gene delivery through its durable transgene expression and safety profile. Among many serotypes, AAV2-retro is typically utilized for dissecting neural circuits with its retrograde functionality. However, this vector requires a relatively long-term incubation period (over 2 weeks) to obtain enough gene expression levels presumably due to low efficiency in gene transduction.

Evolutionary innovations of human cerebral cortex viewed through the lens of high-throughput sequencing.

Humans had acquired a tremendously enlarged cerebral cortex containing a huge quantity and variety of cells during evolution. Such evolutionary uniqueness offers a neural basis of our cognitive innovation and human-specific features of neurodevelopmental and psychiatric disorders. Since human brain is hardly examined in vivo with experimental approaches commonly applied on animal models, the recent advancement of sequencing technologies offers an indispensable viewpoint of human brain anatomy and development.

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively.

Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease that is characterized by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells. The wide range of clinical manifestations in NIID makes ante-mortem diagnosis difficult, but skin biopsy enables its ante-mortem diagnosis. The average onset age is 59.

Molecular drivers of human cerebral cortical evolution.

One of the most important questions in human evolutionary biology is how our ancestor has acquired an expanded volume of the cerebral cortex, which may have significantly impacted on improving our cognitive abilities. Recent comparative approaches have identified developmental features unique to the human or hominid cerebral cortex, not shared with other animals including conventional experimental models. In addition, genomic, transcriptomic, and epigenomic signatures associated with human- or hominid-specific processes of the cortical development are becoming identified by virtue of technical progress in the deep nucleotide sequencing.

Human-Specific NOTCH2NL Genes Expand Cortical Neurogenesis through Delta/Notch Regulation.

The cerebral cortex underwent rapid expansion and increased complexity during recent hominid evolution. Gene duplications constitute a major evolutionary force, but their impact on human brain development remains unclear. Using tailored RNA sequencing (RNA-seq), we profiled the spatial and temporal expression of hominid-specific duplicated (HS) genes in the human fetal cortex and identified a repertoire of 35 HS genes displaying robust and dynamic patterns during cortical neurogenesis.

Stress-induced unfolded protein response contributes to Zika virus-associated microcephaly.

Accumulating evidence support a causal link between Zika virus (ZIKV) infection during gestation and congenital microcephaly. However, the mechanism of ZIKV-associated microcephaly remains unclear. We combined analyses of ZIKV-infected human fetuses, cultured human neural stem cells and mouse embryos to understand how ZIKV induces microcephaly.

Is this a brain which I see before me? Modeling human neural development with pluripotent stem cells.

The human brain is arguably the most complex structure among living organisms. However, the specific mechanisms leading to this complexity remain incompletely understood, primarily because of the poor experimental accessibility of the human embryonic brain. Over recent years, technologies based on pluripotent stem cells (PSCs) have been developed to generate neural cells of various types.

A common developmental plan for neocortical gene-expressing neurons in the pallium of the domestic chicken Gallus gallus domesticus and the Chinese softshell turtle Pelodiscus sinensis.

The six-layered neocortex is a unique characteristic of mammals and likely provides the neural basis of their sophisticated cognitive abilities. Although all mammalian species share the layered structure of the neocortex, the sauropsids exhibit an entirely different cytoarchitecture of the corresponding pallial region. Our previous gene expression study revealed that the chicken pallium possesses neural subtypes that express orthologs of layer-specific genes of the mammalian neocortex.

Novel and robust transplantation reveals the acquisition of polarized processes by cortical cells derived from mouse and human pluripotent stem cells.

Current stem cell technologies have enabled the induction of cortical progenitors and neurons from embryonic stem cells (ESCs) and induced pluripotent stem cells in vitro. To understand the mechanisms underlying the acquisition of apico-basal polarity and the formation of processes associated with the stemness of cortical cells generated in monolayer culture, here, we developed a novel in utero transplantation system based on the moderate dissociation of adherens junctions in neuroepithelial tissue. This method enables (1) the incorporation of remarkably higher numbers of grafted cells and (2) quantitative morphological analyses at single-cell resolution, including time-lapse recording analyses.

Neocortical neurogenesis is not really "neo": a new evolutionary model derived from a comparative study of chick pallial development.

The neocortex facilitates mammalian adaptive radiation by conferring highly sophisticated cognitive and motor abilities. A unique feature of the mammalian neocortex is its laminar structure in which similar neuronal subtypes are arranged in tangential layers and construct columnar circuits via interlaminar connections. The neocortical layer structure is completely conserved among all mammalian species, including monotremes and marsupials.

Evolutionary conservation of neocortical neurogenetic program in the mammals and birds.

The unique innovation of the layered neocortex in mammalian evolution is believed to facilitate adaptive radiation of mammalian species to various ecological environments by furnishing high information processing ability. There are no transitional states from the non-mammalian simple brain to the mammalian multilayered neocortex, and thus it is totally a mystery so far how this brain structure has been acquired during evolution. In our recent study, we found the evidence showing that the evolutionary origin of the neocortical neuron subtypes predates the actual emergence of layer structure.

The temporal sequence of the mammalian neocortical neurogenetic program drives mediolateral pattern in the chick pallium.

The six-layered neocortex permits complex information processing in all mammalian species. Because its homologous region (the pallium) in nonmammalian amniotes has a different architecture, the ability of neocortical progenitors to generate an orderly sequence of distinct cell types was thought to have arisen in the mammalian lineage. This study, however, shows that layer-specific neuron subtypes do exist in the chick pallium.