Biology subjects

Nonaka, M.

Publications and source records attributed to Nonaka, M..

5 recordsLinked to original sources

bioRxiv2025

Neural Progenitors as a Novel Pathogenic Mechanism in Microcephaly

Despite their significance, the genetic and molecular bases of neurodevelopmental disorders remain poorly understood. In this study, using human brain organoids and mouse models, we show that loss of NDE1, a gene closely associated with microcephaly, disrupts progenitor identity, prolongs mitosis, and alters regional patterning in the forebrain. NDE1 knockout leads to a caudal identity shift of neural progenitor cells in the organoids and mouse brains, coinciding with aberrant ERK signaling. Notably, downstream activation of the ERK pathway restored rostral PAX6 expression in human brain organoids. Parallel analyses of Nde1 knockout mice confirmed disrupted regional patterning of the forebrain. Together, our data establish NDE1 as a critical regulator of early human brain regionalization and elucidate molecular mechanisms underlying the structural abnormalities observed in NDE1-associated microcephaly.

developmental biology↗

bioRxiv2025

Trace-DNA from a century-old holotype specimen resolves taxonomic uncertainties: the case of the Hawaiian pink precious coral (Pleurocorallium secundum), a CITES-listed species used in jewelry

The holotype specimen holds the most authentic characteristics of a species; its features will serve as a foundation for the identification of individuals belonging to this species. The precious coral Pleurocorallium secundum was described in 1846 based on a colony from the Hawaiian Islands. This specimen has been preserved; however, it is decorticated and contains exclusively the axial skeleton, which has hindered its use for accurate species identification. Therefore, the species was redescribed in 1956 based on a specimen lot collected in 1902. Pleurocorallium secundum was considered the most frequently fished precious coral species in the second half of the 20th century with landings on the scale of thousands of tons, which was followed by its listing on CITES Appendix III. Recently, the conspecificity of the holotype and the redescribed colonies was questioned and specimens labeled in the scientific literature as P. secundum were discovered to be phylogenetically distant from each other. To clarify the identity of P. secundum, we took minimally destructive samples from the century-old holotype and the redescribed colonies and applied techniques conforming to low copy number DNA analyses. DNA sequences of three mitochondrial regions were evaluated in a phylogenetic framework together with DNA sequences retrieved from freshly collected putative P. secundum specimens and sequences from the scientific literature. The results of this study clearly indicate that the holotype and the redescribed colonies of P. secundum represent the same species. Based on the specimens confirmed to be P. secundum with genetic evidence, the distribution area of P. secundum stretches from the Hawaiian Islands to the South China Sea. At the same time, our analysis uncovered both published and fresh specimens that are in fact not P. secundum. The latter includes the fished Makapuu coral bed in Hawaii, which used to be a significant coral fishing area. Based on the microscopic analysis of the redescribed colonies, we complement the diagnosis of P. secundum. This, together with our genetic results will aid the identification of coral objects present in the international jewelry trade by providing authentic molecular barcoding markers and morphologic features for the identification of P. secundum. Statements and DeclarationsThe authors have no competing interests to declare that are relevant to the content of this article.

zoology↗

bioRxiv2022

Error-acceptable vertical transmission fostered uncoupled phylogenetic relationships between longicorn beetles and their symbionts

The Coleoptera Cerambycidae (longicorn beetles) use wood under different states (living healthy, freshly snapped, completely rot, etc.) in a species-specific manner for their larval diet. Larvae of some Cerambycidae groups have mycetomes, accessory organs associated with the midgut that harbor fungal symbiont cells. The symbionts are thought to improve nutrient conditions; however, this has yet to be shown experimentally. To deduce the evolutionary history of this symbiosis, we investigated the characteristics of the mycetomes in the larvae of longicorn beetles collected in Japan. Lepturinae, Necydalinae, and Spondylidinae are the only groups that possess mycetomes, and these three groups mycetomes and corresponding fungal cells exhibit different characteristics between the groups. However, the phylogenetic relationship of symbiont yeasts does not coincide with that of the corresponding longicorn beetle species, suggesting they have not co-speciated. The imperfect vertical transmission of symbiont yeasts from female to offspring is a mechanism that could accommodate the host-symbiont phylogenetic incongruence. Some Lepturinae species secondarily lost mycetomes. The loss is associated with their diet choice, suggesting that different conditions between feeding habits could have allowed species to discard this organ. We found that symbiont fungi encapsulated in the mycetomes are dispensable for larval growth if sufficient nutrients are given, suggesting that the role of symbiotic fungi could be compensated by the food larvae take. Aegosoma sinicum is a longicorn beetle classified to the subfamily Prioninae, which does not possess mycetomes. However, this species contains a restricted selection of yeast species in the larval gut, suggesting that the symbiosis between longicorn beetles and yeasts emerged before acquiring the mycetomes.

ecology↗

bioRxiv2020

Development of an orally-administrable tumor vasculature-targeting therapeutic using annexin A1-binding D-peptides

IF7 peptide, which binds to the annexin A1 (ANXA1) N-terminal domain, functions as a tumor vasculature-targeted drug delivery vehicle after intravenous injection. To enhance IF7 stability in vivo, we undertook mirror-image peptide phage display using a synthetic D-peptide representing the Anxa1 N-terminus as target. Peptide sequences were identified, synthesized as D-amino acids, and designated as dTIT7, which was shown to bind the ANXA1 N-terminus. Whole body imaging of mouse brain tumors modeled with near infrared fluorescent IRDye-conjugated dTIT7 showed fluorescent signals in brain and kidney. Furthermore, orally-administered geldanamycin (GA)-conjugated dTIT7 suppressed brain tumor growth. Ours is a proof-of-concept experiment showing that Anxa1-binding D-peptide could be developed as an orally-administrable, tumor vasculature-targeted therapeutic. Role of each author: MN designed and performed experiments, analyzed data, and wrote the manuscript; HMA and DLJ produced recombinant ANXA1 protein; KY conducted NMR analysis and data analysis; TOA designed, performed and analyzed LC-MS/MS data; MN, TS, IKT, YS, and TY analyzed peptide-binding assays and performed in silico structural analysis; CTU produced lentivirus for luciferase expression; CNH performed peptide binding assays, tissue culture and animal experiments; and MNF supervised the project and wrote the manuscript.

pharmacology and toxicology↗

bioRxiv2017

2D:4D and spatial abilities: From rats to humans

Variance in spatial abilities are thought to be determined by in utero levels of testosterone and oestrogen, measurable in adults by the length ratio of the 2nd and 4th digit (2D:4D). We confirmed the relationship between 2D:4D and spatial performance using rats in two different tasks (paired-associate task and watermaze) and replicated this in humans. We further clarified anatomical and functional brain correlates of the association between 2D:4D and spatial performance in humans.

neuroscience↗