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Shimamura, K.

Publications and source records attributed to Shimamura, K..

4 recordsLinked to original sources

A conserved lamination pattern in the paleocortex and the neocortex revealed by single-cell RNA analyses

The piriform cortex, the largest paleocortical domain and a central olfactory cortex, is classically described as a three-layered structure, with layer II subdivided into semilunar and superficial pyramidal neurons. However, its cellular composition, developmental logic, and evolutionary relationship with the six-layered neocortex remain incompletely defined. Here, we aimed to resolve piriform cortical cell types and laminar organization and compare their molecular programs across mammalian cortical regions and the reptilian cortex. We performed single-nucleus RNA sequencing of the microdissected piriform cortex and integrated neuronal lineage data with published datasets, with spatial validation via the Allen Mouse Brain Atlas. Interspecies analyses identified piriform-dominant glutamatergic populations marked by Unc13c/Lmo3/Rora and an Rorb/Reln/Ntng1-enriched sensory-recipient subtype localized to the superficial layer IIa, consistent with semilunar neurons. Spatial transcriptomic mapping revealed that piriform layer IIb contains neocortical upper-layer-like corticocortical neurons, while piriform layer III segregates into layer V-like (IIIa), layer VI-like (IIIb), and VIb/VII (subplate)-equivalent populations, indicating a neocortex-like laminar framework with an inverted positioning of sensory recipients and corticocortical compartments relative to the neocortex. GABAergic neurons largely conformed to canonical MGE- and CGE-derived lineages but included a piriform-specific Rgs9+Pde7b+ subtype consistent with an LGE-related origin, suggesting region-specific diversification of GABAergic neurons. Disease ontology enrichment linked hippocampus-dominant glutamatergic programs to Alzheimers-related genes and piriform-dominant (and pan-cortical) excitatory and inhibitory programs to autism spectrum disorder and intellectual disability, implicating coordinated E/I circuit specializations in area-selective vulnerability. These findings support a revised view of the paleocortex as a divergent specialization of a conserved, multilayered cortical program and provide molecular markers and a comparative framework for studying cortical evolution and region-specific disease susceptibility.

developmental biology↗

Computed Tomography-Derived Elastic Modulus as a Noninvasive Marker of Aortic Wall Integrity: Correlation with Histopathology in the Ascending Aorta

BackgroundAscending aortic aneurysms and dissections are life-threatening conditions often requiring prophylactic surgeries. Current guidelines rely primarily on aortic diameter for intervention; however, many dissections occur without severe dilation. Mechanical properties, such as elastic modulus have emerged as potential predictors of disease progression; nonetheless, noninvasive clinical applications remain limited. This study evaluated the relationship between the computed tomography (CT)-derived elastic modulus of the ascending aorta and the histopathological characteristics of the aortic media. MethodsThirty patients who underwent surgical ascending aorta replacement were included in this study. Preoperative CT was used to calculate the aortic elastic modulus based on geometric measurements and pulse pressure. Resected aortic specimens were subjected to histological and immunohistochemical analyses to assess elastin, collagen, vascular smooth muscle cells (VSMCs), and smoothelin expression. Correlation analyses between the CT-derived elastic modulus and aortic media composition were conducted after adjusting for age and aortic diameter. ResultsThe CT-derived elastic modulus exhibited a significant negative correlation with elastin area and a positive correlation with collagen area. Additionally, a moderate negative correlation was observed between the elastic modulus and elastin fiber waviness. A strong negative correlation was detected between the elastic modulus and the proportion of contractile-type (smoothelin-positive) VSMCs. These findings remained significant after adjusting for confounders. ConclusionsCT-derived elastic modulus of the ascending aorta reflects the underlying pathological changes, including extracellular matrix remodeling and VSMC phenotypic modulation. Noninvasive assessment of aortic mechanical properties may provide novel insights into aortic disease progression and therapeutic responses.

pathology↗

Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms to control cell motility and neurite outgrowth

Microtubule (MT) dynamics are modulated through the coordinated action of various MT-associated proteins (MAPs). However, the regulatory mechanisms underlying MT dynamics remain unclear. We show that the MAP7 family protein Map7D2 stabilizes MTs to control cell motility and neurite outgrowth. Map7D2 directly bound to MTs through its N-terminal half and stabilized MTs in vitro. Map7D2 localized prominently to the centrosome and partially on MTs in mouse N1-E115 neuronal cells, which expresses two of the four MAP7 family members, Map7D2 and Map7D1. Map7D2 loss decreased the resistance to the MT-destabilizing agent, nocodazole without affecting acetylated/detyrosinated stable MTs, suggesting that Map7D2 stabilizes MTs via direct binding. In addition, Map7D2 loss increased the rate of random cell migration and neurite outgrowth, presumably by disturbing the balance between MT stabilization and destabilization. Map7D1 exhibited similar subcellular localization and gene knock-down phenotypes to Map7D2. However, in contrast to Map7D2, Map7D1 was required for the maintenance of acetylated stable MTs. Taken together, our data suggest that Map7D2 and Map7D1 facilitate MT stabilization through distinct mechanisms in cell motility and neurite outgrowth.

cell biology↗

Thalamocortical axons control the cytoarchitecture of neocortical layers by area-specific supply of secretory proteins

Neuronal abundance and thickness of each cortical layer is specific to each area, but how this fundamental feature arises during development remains poorly understood. While some of area-specific features are controlled by intrinsic cues such as morphogens and transcription factors, the exact influence and mechanisms of action by extrinsic cues, in particular the thalamic axons, have not been fully established. Here we identify a thalamus-derived factor, VGF, which is indispensable for thalamocortical axons to maintain the proper amount of layer 4 neurons in the mouse sensory cortices. This process is prerequisite for further maturation of the primary somatosensory area, such as barrel field formation instructed by a neuronal activity-dependent mechanism. Our results also provide an insight into regionalization of brain in that highly site-specific axon projection anterogradely confers further regional complexity upon the target field through locally secreting signaling molecules from axon terminals.

neuroscience↗