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Early role for a Na <sup>+</sup> ,K <sup>+</sup> -ATPase ( <i>ATP1A3</i> ) in brain development

Richard S. Smith, Marta Florio, Shyam K. Akula, Jennifer E. Neil, Yidi Wang, Robert Hill, Melissa Goldman, Christopher D. Mullally, Nora Reed, Luis Bello‐Espinosa, Laura Flores‐Sarnat, Fabíola Paoli Monteiro, Erasmo Barbante Casella, Filippo Pinto e Vairo, Éva Morava, A. James Barkovich, Joseph Gonzalez–Heydrich, Catherine A. Brownstein, Steven A. McCarroll, Christopher A. Walsh

2021Proceedings of the National Academy of Sciences58 citationsDOIOpen Access PDF

Abstract

Significance By evaluating children with a malformed cerebral cortex, we identified an ATPase pump (ATP1A3) with an early role in brain development. The ATP1A3 pump maintains the physiological concentration of sodium and potassium ions in cells, a process critical for osmotic equilibrium and membrane potential across several developing cell populations. We employed single-cell sequencing approaches to identify key enrichments for ATP1A3 expression during human cortex development. Unravelling this early cell-type–specific pathophysiology in the developing brain offers a potential basis for the treatment of ATP1A3 -related diseases affecting prenatal and early childhood development.

Topics & Concepts

SubplateNeocortexBiologyNeuroscienceCerebral cortexIn situ hybridizationCell biologyParvalbuminGene expressionInternal medicineBiochemistryGeneMedicineMicroRNA in disease regulationIon Transport and Channel RegulationSingle-cell and spatial transcriptomics