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Garma, L.

Publications and source records attributed to Garma, L..

2 recordsLinked to original sources

CONSERVED NUCLEAR MORPHOLOGY IDENTIFIES FUNCTIONAL RADIAL GLIA NEURAL PROGENITORS

Mechanical cues influence neural development, yet how tissue architecture is integrated into progenitor cell states remains poorly understood. Here, we show that defined microtopographies induce an early nuclear remodeling program associated with radial glia (RG)-like competence. Aligned microgrooves promote nuclear elongation, reduced Lamin A/C to B1 ratio, sustained {beta}-catenin activity, and distinct patterns of nuclear calcium dynamics, all of which merge before peak Pax6 expression. Pharmacological inhibition of mechanosensitive calcium signaling abolishes RG-associated marker induction while preserving nuclear remodeling, indicating that calcium-dependent pathways are required for Pax6 induction but are dispensable for the establishment of the underlying morphometric state. To quantitatively describe these transitions, we developed an interpretable model based on nuclear geometry and local cell density that identifies morphometric states associated with RG-like competence across experimental conditions. Application of this framework to embryonic mouse and human cortex revealed analogous signatures in native RG populations. Together, these findings indicate that tissue architecture influences RG-like competence through conserved nuclear morphometric states across developmental contexts.

developmental biology↗

Interneuron diversity in the human dorsal striatum

Deciphering the striatal interneuron diversity is key to understanding the basal ganglia circuit and to untangle the complex neurological and psychiatric diseases affecting this brain structure. We performed single-nucleus RNA-sequencing (snRNA-seq) of postmortem human caudate nucleus (CN) and putamen (Pu) samples to elucidate the diversity and abundance of interneuron populations and their transcriptional structure in the human dorsal striatum. We propose a new taxonomy of striatal interneurons with eight main classes. We provide specific markers for all subclasses and validated some of them with quantitative in situ fluorescence hybridization, such as a novel PTHLH-expressing population that exhibits different abundance and gene expression between CN and Pu. For the most abundant interneuron populations in human striatum, PTHLH and TAC3, we found matching known mouse interneuron populations based on key functional genes such as ion channels and synaptic receptors. Remarkably, human TAC3 and mouse Th populations share important similarities including the expression of the neuropeptide tachykinin 3. Finally, we were able to integrate our dataset with several prior smaller human striatal snRNA-seq studies, thus supporting the generalizability of this new harmonized taxonomy.

neuroscience↗