Takuya Imamura

Whereas primate-specific genes are known to drive human evolution, conserved genes also play critical roles in defining species-specific traits. This study identifies MEIS1 as a key conserved gene with significantly higher expression in human radial glia compared with those in mice. Our functional analysis revealed that MEIS1 knockdown (KD) in human cerebral organoids leads to premature neural differentiation. Conversely, MEIS1 overexpression in the mouse brain significantly increases the abundance of neural progenitor cells (NPCs). By investigating a noncoding RNA (ncRNA) partner derived from the MEIS1 promoter, we demonstrated that its KD triggers MEIS1 down-regulation, markedly reducing NPC proliferative capacity. RNA-sequencing further indicated that MEIS1 regulates genes involved in cholesterol biogenesis. Specifically, forced expression of DHCR7 , a MEIS1 -target gene, rescued both the proliferative deficits and the reduction in primary cilia length induced by MEIS1 KD. These findings suggest that ncRNA-mediated regulatory mechanism for the conserved MEIS1 coordinates primary cilia morphology and cholesterol metabolism. This coordination is essential for maintaining long-term NPC properties, ultimately contributing to the evolutionary expansion of the human cerebral cortex.

Bonobos (Pan paniscus), which share a close evolutionary lineage with chimpanzees (Pan troglodytes) and humans, offer vital insights into the genetic and d

AUTS2 syndrome is characterized by intellectual disability and microcephaly, and is often associated with autism spectrum disorder, but the underlying mechanisms, particularly concerning microcephaly, remain incompletely understood. Here, we analyze mice mutated for the transcriptional regulator AUTS2, which recapitulate microcephaly. Their brains exhibit reduced division of intermediate progenitor cells (IPCs), leading to fewer neurons and decreased thickness in the upper-layer cortex. Increased expression of the AUTS2 transcriptional target Robo1 in the mutant animals suppresses IPC division, and transcriptomic and chromatin profiling shows that AUTS2 primarily represses transcription of genes like Robo1 in IPCs. Regions around the transcriptional start sites of AUTS2 target genes are enriched for the repressive histone modification H3K27me3, which is reduced in Auts2 mutants. Furthermore, we find that AUTS2 interacts with Polycomb complex PRC2, with which it cooperates to promote IPC division. These findings shed light on the microcephaly phenotype observed in the AUTS2 syndrome.

The sea squirt Ciona robusta (formerly Ciona intestinalis type A) has been the subject of many interdisciplinary studies. Known as a vanadium-rich ascidian, C. robusta is an ideal model for exploring microbes associated with the ascidian and the roles of these microbes in vanadium accumulation and reduction. In this study, we discovered two bacterial strains that accumulate large amounts of vanadium, CD2-88 and CD2-102, which belong to the genera Pseudoalteromonas and Vibrio, respectively. The growth medium composition impacted vanadium uptake. Furthermore, pH was also an important factor in the accumulation and localization of vanadium. Most of the vanadium(V) accumulated by these bacteria was converted to less toxic vanadium(IV). Our results provide insights into vanadium accumulation and reduction by bacteria isolated from the ascidian C. robusta to further study the relations between ascidians and microbes and their possible applications for bioremediation or biomineralization.

Vertebrate animals often exhibit sexual dimorphism in body shape. In mammals, decreases in sex hormones caused by testicular castration can affect body shape and occasionally lead to pathologies such as obesity. Post-castration obesity can also be problematic for the health of companion animals, including non-mammals. In order to understand the mechanism of post-castration obesity in vertebrates other than mammals, experimental models are required. We examined whether the Iberian ribbed newt, which has recently become a popular experimental model for amphibian research, could serve as a model for analyzing changes in body shape after castration. In newts, new testes can be regenerated after removal of differentiated testes. We analyzed changes in body shape by removing the testes under conditions in which they could regenerate or conditions in which they could not regenerate. Removal of the testes reduced blood testosterone levels. The body weight and abdominal girth of the newts were increased compared with normal male newts. Transcriptome analysis of the liver showed that a set of genes related to lipid metabolism was continuously up-regulated in castrated newts. Our study suggests that changes in body shape after castration are common in vertebrates. Iberian ribbed newts are thus a suitable model for comparative studies of the long-term physiologic- and endocrine-level effects of castration.

Cortical expansion has occurred during human brain evolution. By comparing human and mouse RNA‐seq datasets, we found that transmembrane protein 25 ( TMEM25 ) was much more highly expressed in human neural progenitors (NPCs). Overexpression of either human TMEM25 or mouse Tmem25 similarly promoted mouse NPC proliferation in vitro . Mimicking human‐type expression of TMEM25 in mouse ventricular cortical progenitors accelerated proliferation of basal radial glia (bRG) and increased the number of upper‐layer neurons in vivo . By contrast, RNA‐seq analysis, and pharmacological assays showed that knockdown of TMEM25 in cultured human NPCs compromised the effects of extracellular signals, leading to cell cycle inhibition via Akt repression. Thus, TMEM25 can receive extracellular signals to expand bRG in human cortical development.

Microcephaly is characterized as a small head circumference, and is often accompanied by developmental disorders. Several candidate risk genes for this disease have been described, and mutations in non-coding regions are occasionally found in patients with microcephaly. Various non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), SINEUPs, telomerase RNA component (TERC), and promoter-associated lncRNAs (pancRNAs) are now being characterized. These ncRNAs regulate gene expression, enzyme activity, telomere length, and chromatin structure through RNA binding proteins (RBPs)-RNA interaction. Elucidating the potential roles of ncRNA-protein coordination in microcephaly pathogenesis might contribute to its prevention or recovery. Here, we introduce several syndromes whose clinical features include microcephaly. In particular, we focus on syndromes for which ncRNAs or genes that interact with ncRNAs may play roles. We discuss the possibility that the huge ncRNA field will provide possible new therapeutic approaches for microcephaly and also reveal clues about the factors enabling the evolutionary acquisition of the human-specific “large brain.”

Consecutive sexual maturation (CSM), an abnormal reproductive phenomenon of a marine snail, Reishia clavigera, has occurred since 2017 in the vicinity of the Fukushima Daiichi Nuclear Power Plant after the nuclear disaster there. We hypothesized that alterations in animal physiology mediated through genetic/epigenetic changes could sensitively reflect environmental pollution. Understanding the mechanism of this rapid biological response should enable us to quantitatively evaluate long-lasting effects of the nuclear disaster. To determine the molecular basis for CSM, we conducted transcriptome profiling in the ganglia of normal and CSM snails. We assembled the short-read cDNA sequences obtained by Illumina sequencing, and succeeded in characterizing more than 60,000 gene models that include 88 kinds of neuropeptide precursors by BLAST search and experimental curation. GO-enrichment analysis of the differentially expressed genes demonstrated that severe downregulation of neuropeptide-related genes occurred concomitantly with CSM. In particular, significant decreases of the transcripts of 37 genes among 88 neuropeptide precursor genes, including those for myomodulin, PentaFVamide, maturation-associated peptide-5A and conopressin, were commonly observed in female and male CSM snails. By contrast, microseminoprotein precursor was the only exceptional case where the expression was increased in CSM snails. These results indicate that down-regulation of neuropeptide precursors is a remarkable feature of CSM. We also found that factors involved in epigenetic modification rather than transcription factors showed altered patterns of expression upon CSM. Comprehensive expression panels of snail neuropeptide precursors made in this study will be useful tools for environmental assessment as well as for studying marine reproductive biology.

Increasing evidence has shown that many long non-coding RNAs (lncRNAs) are involved in gene regulation in a variety of ways such as transcriptional, post-transcriptional and epigenetic regulation. Promoter-associated non-coding RNAs (pancRNAs), which are categorized into the most abundant single-copy lncRNA biotype, play vital regulatory roles in finely tuning cellular specification at the epigenomic level. In short, pancRNAs can directly or indirectly regulate downstream genes to participate in the development of organisms in a cell-specific manner. In this review, we will introduce the evolutionarily acquired characteristics of pancRNAs as determined by comparative epigenomics and elaborate on the research progress on pancRNA-involving processes in mammalian embryonic development, including neural differentiation.