Biology subjects

Ohtaka-Maruyama, C.

Publications and source records attributed to Ohtaka-Maruyama, C..

6 recordsLinked to original sources

bioRxiv2026

Mosaic evolution of avian brain compartments revealed by comparative MRI

Birds evolved large, cognitively capable forebrains independently of mammals, yet comparative analyses of avian brain organization have been constrained by the lack of standardized resources capable of resolving internal parcellation and long-range connectivity across species. Here, we present a comparative MRI resource spanning 16 avian species representing major clades and diverse ecological niches. We analyzed high-resolution T2-weighted and diffusion-weighted datasets suitable for direct interspecific comparison. T2-weighted morphometry revealed pronounced region-specific variation in internal brain architecture, including lineage-dependent differences in the relative prominence of major brain divisions and commissural structures, supporting a pattern of mosaic diversification rather than uniform scaling. To validate MRI-derived anatomical boundaries, we compared MRI parcellations with complementary histological analyses in three representative taxa (the large-billed crow, gentoo penguin, and mandarin duck), demonstrating close correspondence between MRI-defined borders and cytoarchitectonic transitions identified by Nissl staining, as well as major myelinated compartments visualized by Luxol Fast Blue staining. Moreover, diffusion MRI tractography and fractional anisotropy (FA) mapping further revealed both conserved and species-specific features of large-scale brain organization. Seed-based tractography of the optic lobe, dorsal cortex, cerebellum, and anterior cortex in chick, gentoo penguin, and large-billed crow revealed conserved within-compartment trajectory patterns alongside marked region-specific interspecific differences, particularly in optic-lobe-associated long-range trajectories. Whole-brain FA maps revealed complementary variation in regional microstructural organization across taxa. Together, this comparative MRI framework provides a cross-validated foundation for linking internal brain anatomy and long-range connectivity to ecological and evolutionary diversification in birds, with broader applications to comparative neuroanatomy across amniotes. Significance StatementHow does the internal architecture of the brain reorganize as species adapt to diverse lifestyles? Traditional comparative neuroanatomy has largely relied on overall brain size and external morphology, providing limited insight into internal subdivisions and long-range connectivity. In this study, we present a standardized avian MRI resource and a reproducible analytical pipeline that enables direct cross-species comparisons of 3D morphometry and diffusion-derived connectivity across 16 bird species representing major clades and diverse ecological niches. MRI-derived anatomical boundaries are validated through complementary histological analyses, providing biological support for cross-species parcellation and white-matter measurements. Using this framework, we demonstrate that avian brains diversify in a strongly mosaic manner, with region-and pathway-specific changes that vary disproportionately across lineages rather than scaling uniformly with overall brain size. By moving beyond simple correlations between brain size and behavior, this resource provides a benchmark for testing hypotheses of mosaic brain evolution and for linking neural architecture to ecological and behavioral diversification across vertebrates.

zoology↗

bioRxiv2026

Dual Developmental Origins and Activity-dependent Specification of Mammalian Subplate Neurons

Subplate neurons (SpNs) are among the earliest-generated cortical neurons and are essential for neocortical circuit assembly. Despite this central role, they have long been considered a mammalian innovation, yet their evolutionary origin remains unresolved. Here, using comparative single-cell and spatial transcriptomics across amniotes (mice, chicks, and turtles), we identify two distinct developmental and evolutionary origins of SpNs: atypical SpNs (aSpNs), an Nr4a2-negative population conserved across amniotes and originating from the medial pallium, and mammalian-type SpNs (mSpNs), an Nr4a2-positive population preferentially expanded in mammals and arising from early-born cortical neurons. Cross-species analyses show that early-born pallial neurons in non-mammalian amniotes differentiate into thalamic input neurons, whereas this ancestral program is repurposed in mammals, with early-born neurons transiently adopting a subplate identity. We further show that this fate switch is controlled by Zbtb18 repression linked to thalamic input. Collectively, these findings establish a dual-origin model for SpNs and provide a unifying framework for understanding neocortical evolution. One-Sentence SummaryDevelopmental rewiring of an ancestral input-neuron program gave rise to the mammalian subplate.

evolutionary biology↗

bioRxiv2025

Most early-born subplate neurons persist as Layer 6b neurons in the adult mouse neocortex

Subplate neurons (SpNs) are among the earliest-born neurons in the mammalian neocortex and play key roles in radial migration and transient circuit formation. It has long been assumed that most SpNs undergo extensive postnatal cell death, leaving only a small remnant population that contributes to layer 6b (L6b) in adulthood. However, the extent to which SpNs actually persist as L6b neurons has remained unresolved, partly because previous studies lacked quantitative, whole-cortex analyses that account for postnatal cortical expansion. Here, we performed a comprehensive birthdating analysis using multiple EdU injections spanning the entire neurogenic window of SpNs in mice, combined with whole-neocortex 3D tissue clearing to measure subplate and L6b volumes. This approach allowed us to directly estimate the total number and distribution of SpN-derived neurons in adulthood. We found that most early-born SpNs persist as L6b neurons, and that the apparent postnatal reduction in SpN density reflects tangential cortical expansion rather than neuronal loss. Moreover, surviving SpNs comprise diverse neuronal subtypes reminiscent of those present at early postnatal stages. Together, these findings demonstrate that, in rodents, the majority of adult L6b neurons originate from SpNs, revising the long-held view that the subplate is a largely transient neuronal population.

neuroscience↗

bioRxiv2024

Conserved interhemispheric morphogenesis in amniotes preceded the evolution of the corpus callosum

The corpus callosum (CC) is the large axon bundle connecting the telencephalic hemispheres. The CC is formed exclusively in placental mammals, and the lack of comparable structures in other amniotes obscures the evolutionary origin of the CC. We here demonstrate that interhemispheric remodeling, a prior developmental step for CC formation, is highly conserved in non-mammalian amniotes, such as reptiles and birds. In these animal groups, the spatiotemporal dynamics of interhemispheric remodeling are tightly connected with distinct commissural formations. We observed a high degree of similarity between the mammalian CC and reptilian rostral pallial commissure, (RPC) and significant modifications in the avian pallial projection. Furthermore, we determined that Satb2 plays crucial roles in interhemispheric remodeling, which is associated with proper formation of both the CC and RPC in mice and geckoes, via the use of CRISPR-mediated gene-targeting. Our findings suggest that developmental mechanisms for midline remodeling were already present in the common ancestor of amniotes, which contributed to the evolution of eutherian-specific CC formation.

developmental biology↗

bioRxiv2023

Spatial transcriptome of developmental mouse brain reveals temporal dynamics of gene expressions and heterogeneity of the claustrum

During the development of the mammalian cerebral cortex, numerous neurons are arranged in a six-layer structure with an inside-out fashion to form the neocortex and wire neural circuits. This process includes cell proliferation, differentiation, migration, and maturation, supported by precise genetic regulation. To understand this sequence of processes at the cellular and molecular levels, it is necessary to characterize the fundamental anatomical structures by gene expression. However, markers established in the adult brain sometimes behave differently in the fetal brain, actively changing during development. Spatial transcriptomes yield genome-wide gene expression profiles from each spot patterned on tissue sections, capturing RNA molecules from fresh-frozen sections and enabling sequencing analysis while preserving spatial information. However, a deeper understanding of this data requires computational estimation, including integration with single-cell transcriptome data and aggregation of spots on the single-cell cluster level. The application of such analysis to biomarker discovery has only begun recently, and its application to the developing fetal brain is largely unexplored. In this study, we performed a spatial transcriptome analysis of the developing mouse brain to investigate the spatiotemporal regulation of gene expression during development. Using these data, we conducted an integrated study with publicly available mouse data sets, the adult brains spatial transcriptome, and the fetal brains single-cell transcriptome. Our data-driven analysis identified novel molecular markers of the choroid plexus, piriform cortex, thalamus, and claustrum. In addition, we revealed that the internal structure of the embryonic claustrum is composed of heterogeneous cell populations.

developmental biology↗

bioRxiv2022

ADAMTS2 regulates radial neuronal migration by activating TGF-β signaling at the subplate layer of the developing neocortex

During the development of the mammalian brain, neocortical structures are formed by the sequential radial migration of newborn excitatory neurons. The early migrating neurons exhibit a multipolar shape, but they undergo a multipolar-to-bipolar transition at the subplate (SP) layer, where extracellular matrix (ECM) components are abundantly expressed. In this study, we revealed that the TGF-{beta} signaling-related ECM proteins, such as latent TGF-{beta}-binding protein 1 (LTBP1) and fibrillin 2, and TGF-{beta} receptor II (TGF-{beta}RII) and its downstream effector, p-smad2/3, are selectively expressed at the SP layer, suggesting that TGF-{beta} is sequestered in a latent form by forming complexes with these ECM components and then its signaling is activated by ECM remodeling. We found that the migrating multipolar neurons transiently express a disintegrin and metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. Knockdown and knockout of Adamts2 suppressed the multipolar-to-bipolar transition of migrating neurons, and therefore, disturbed radial migration. Similar phenotypes were observed by the perturbation of TGF-{beta} signaling in the migrating neurons. Time-lapse luminescence imaging of TGF-{beta} signaling indicated that ADAMTS2 activates this signaling pathway in the migrating neurons during the multipolar-to-bipolar transition at the SP layer. These results suggest that the ADAMTS2 secreted by the migrating multipolar neurons activates TGF-{beta} signaling by ECM remodeling of the SP layer, leading to the multipolar-to-bipolar transition. We propose that the SP layer plays an essential role in the radial neuronal migration as a signaling center of the developing neocortex. SIGNIFICANCEThe neocortex is formed by the sequential radial migration of newborn neurons, which undergo a multipolar-to-bipolar transition at the subplate (SP) layer. The extracellular matrix (ECM) is abundantly expressed in the SP layer. However, the roles of the ECM in the SP layer have been unclear. We found that migrating neurons transiently express a disintegrin and a metalloproteinase with thrombospondin motif 2 (ADAMTS2), an ECM metalloproteinase, just below the SP layer. We show that ADAMTS2 secreted by multipolar migrating neurons activates TGF-{beta} signaling through remodeling of the ECM in the SP layer, leading to the multipolar-to-bipolar transition. Thus, the SP layer plays an essential role in radial migration as a signaling center of the developing neocortex

neuroscience↗