Biology subjects

Yokota, C.

Publications and source records attributed to Yokota, C..

4 recordsLinked to original sources

bioRxiv2026

SorCS2 controls Wnt signaling homeostasis during neurodevelopment by regulating Ror2 activity and trafficking

Wnt signaling orchestrates key developmental processes, yet mechanisms restricting its spatial and temporal activity remain incompletely understood. Here we identify SorCS2, a VPS10p-domain sorting receptor, as a conserved regulator of Wnt signaling homeostasis. Integrating proteomics, cell biology, embryology, and vertebrate models, we show that SorCS2 interacts with the noncanonical Wnt receptor Ror2 and controls its trafficking, Wnt5a-induced internalization, and lysosomal degradation. In mouse dopaminergic progenitors, SorCS2 deficiency enhances responsiveness to canonical and noncanonical Wnt ligands, increases Ror2 phosphorylation, and amplifies downstream signaling of both Wnt signaling cascades. Loss of SorCS2 further disrupts the ligand-receptor feedback loop, leading to elevated Ror2, Wnt5a, and Wnt1 expression, accelerated proliferation and neurogenesis, and increased expression of Tcf4, a gene implicated in neuropsychiatric disorders. Across vertebrate systems, SorCS2-dependent control of Ror2 signaling is required for anterior-posterior axis elongation, convergent extension, somitogenesis, and brain morphogenesis. These findings define a SorCS2-dependent sorting mechanism that fine-tunes morphogen receptor signaling during vertebrate neurodevelopment.

developmental biology↗

bioRxiv2026

Sympathoadrenal Lineage Plasticity Drives Intratumoral Heterogeneity in Paraganglioma, Neuroblastoma and Composite Tumors Following KIF1Bb-NF1 Loss

Neuroblastoma (NB) and paraganglioma (PPGL) arise from the sympathoadrenal lineage, yet their developmental relationship and heterogeneity remain unclear. Single-cell and spatial transcriptomics revealed shared, spatially organized developmental states, including populations characteristic of the other tumor type, chromaffin-like cells in NB and neuroblast-like cells in PPGL and hybrids co-expressing adjacent states. Deconvolution of an independent PPGL cohort associated metastatic disease most strongly with chromaffin hybrid states, alongside connecting progenitor-like, cycling neuroblast, and early chromaffin identities, whereas non-metastatic tumors were enriched for differentiated late chromaffin identities. In mice, combined loss of the candidate 1p36 tumor suppressor KIF1B{beta} and NF1 recapitulates these developmental architectures by prolonging developmental plasticity, reactivating embryonic neurogenic programs, and driving chromaffin-to-neuroblast transitions generating pheochromocytoma, neuroblastoma and composite tumors. Mouse tumors contained discrete spatial domains of developmental and neoplastic states that mirrored those in human PPGL. Together, our findings establish chromaffin-neuroblast plasticity as a mechanism of sympathoadrenal tumor heterogeneity and identify hybrid developmental states as a potential indicator of plasticity associated with metastatic PPGL.

cancer biology↗

bioRxiv2023

Single cell-resolution in situ sequencing elucidates spatial dynamics of multiple sclerosis lesion and disease evolution

Multiple sclerosis (MS) is a neurological disease characterised by multifocal lesions and smouldering pathology. While single-cell analyses have provided insights into neuropathology, cellular processes underlying MS remain poorly understood. We modelled the cellular dynamics of MS by examining temporal and regional rates of disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model. By performing single-cell spatial expression profiling using In situ sequencing, we annotated disease neighbourhoods during lesion evolution and found centrifugal propagation of active lesions. We demonstrated that disease-associated (DA) glia are dynamic and induced independently of lesions, preceding their formation. Single-cell spatial analysis of human archival MS spinal cord confirmed differential distribution of DA-glia, enabled deconvolution of active and inactive lesions into sub-compartments, and identification of new lesion areas. By establishing a spatial resource of mouse and human MS neuropathology at a single-cell resolution, our study unveils the intricate cellular dynamics underlying MS disease evolution.

cell biology↗

bioRxiv2021

Spatial cell type mapping of the oligodendrocyte lineage in the mouse juvenile and adult CNS with in situ sequencing

Oligodendrocytes show transcriptional heterogeneity but the regional and functional implications of this heterogeneity are less clear. Here, we apply in situ sequencing (ISS) to simultaneously probe the expression of 124 marker genes of distinct oligodendrocyte populations, providing comprehensive maps of corpus callosum, cingulate, motor and somatosensory cortex in the brain, as well as gray (GM) and white matter (WM) regions in the spinal cord, at juvenile and adult stages. We systematically compare abundances of these populations and investigate the neighboring preference of distinct oligodendrocyte populations. As previously described, we observed that oligodendrocyte lineage progression is more advanced in the juvenile spinal cord compared to the brain. Additionally, myelination is ongoing in the adult corpus callosum while it is mostly completed in the cortex. Interestingly, we found a medial-to-lateral gradient of oligodendrocyte lineage progression in the juvenile cortex, which could be linked to arealization, as well as a deep-to-superficial gradient with mature oligodendrocytes preferentially accumulating in the deeper layers of the cortex. We observed differences in abundances and population dynamics over time between GM and WM regions in the brain and spinal cord, indicating regional differences within GM and WM. We also found that oligodendroglia populations neighboring preferences are altered from the juvenile to the adult CNS. Thus, our ISS dataset reveals spatial heterogeneity of the oligodendrocyte lineage progression in the brain and spinal cord, which could be relevant to further investigate functional heterogeneity of oligodendroglia.

neuroscience↗