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Islet1 Precursors Contribute to Mature Interneuron Subtypes in Mouse Neocortex.

  • Siddiqi, Faez1
  • Trakimas, Alexandria L1, 2
  • Joseph, Donald J1, 3
  • Lippincott, Margaret L1
  • Marsh, Eric D1, 3, 2
  • Wolfe, John H1, 3, 2, 4
  • 1 Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.
  • 2 Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 3 Division of Child Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
  • 4 W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Published Article
Cerebral Cortex
Oxford University Press
Publication Date
Jul 06, 2021
DOI: 10.1093/cercor/bhab152
PMID: 34228108


Cortical interneurons (GABAergic cells) arise during embryogenesis primarily from the medial and caudal ganglionic eminences (MGE and CGE, respectively) with a small population generated from the preoptic area (POA). Progenitors from the lateral ganglionic eminence (LGE) are thought to only generate GABAergic medium spiny neurons that populate the striatum and project to the globus pallidus. Here, we report evidence that neuronal precursors that express the LGE-specific transcription factor Islet1 (Isl1) can give rise to a small population of cortical interneurons. Lineage tracing and homozygous deletion of Nkx2.1 in Isl1 fate-mapped mice showed that neighboring MGE/POA-specific Nkx2.1 cells and LGE-specific Isl1 cells make both common and distinct lineal contributions towards cortical interneuron fate. Although the majority of cells had overlapping transcriptional domains between Nkx2.1 and Isl1, a population of Isl1-only derived cells also contributed to the adult cerebral cortex. The data indicate that Isl1-derived cells may originate from both the LGE and the adjacent LGE/MGE boundary regions to generate diverse neuronal progeny. Thus, a small population of neocortical interneurons appear to originate from Isl-1-positive precursors. © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected]

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