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Publication : Developmental trajectories of thalamic progenitors revealed by single-cell transcriptome profiling and Shh perturbation.

First Author  Govek KW Year  2022
Journal  Cell Rep Volume  41
Issue  10 Pages  111768
PubMed ID  36476860 Mgi Jnum  J:332216
Mgi Id  MGI:7410745 Doi  10.1016/j.celrep.2022.111768
Citation  Govek KW, et al. (2022) Developmental trajectories of thalamic progenitors revealed by single-cell transcriptome profiling and Shh perturbation. Cell Rep 41(10):111768
abstractText  The thalamus is the principal information hub of the vertebrate brain, with essential roles in sensory and motor information processing, attention, and memory. The complex array of thalamic nuclei develops from a restricted pool of neural progenitors. We apply longitudinal single-cell RNA sequencing and regional abrogation of Sonic hedgehog (Shh) to map the developmental trajectories of thalamic progenitors, intermediate progenitors, and post-mitotic neurons as they coalesce into distinct thalamic nuclei. These data reveal that the complex architecture of the thalamus is established early during embryonic brain development through the coordinated action of four cell differentiation lineages derived from Shh-dependent and -independent progenitors. We systematically characterize the gene expression programs that define these thalamic lineages across time and demonstrate how their disruption upon Shh depletion causes pronounced locomotor impairment resembling infantile Parkinson's disease. These results reveal key principles of thalamic development and provide mechanistic insights into neurodevelopmental disorders resulting from thalamic dysfunction.
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