Use of "MGE Enhancers" for Labeling and Selection of Embryonic Stem Cell-Derived Medial Ganglionic Eminence (MGE) Progenitors and Neurons

Ying Jiun J. Chen, Daniel Vogt, Yanling Wang, Axel Visel, Shanni N. Silberberg, Cory R. Nicholas, Teruko Danjo, Joshua L. Pollack, Len A. Pennacchio, Stewart Anderson, Yoshiki Sasai, Scott C. Baraban, Arnold R. Kriegstein, Arturo Alvarez-Buylla, John L.R. Rubenstein

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

The medial ganglionic eminence (MGE) is an embryonic forebrain structure that generates the majority of cortical interneurons. MGE transplantation into specific regions of the postnatal central nervous system modifies circuit function and improves deficits in mouse models of epilepsy, Parkinson's disease, pain, and phencyclidine-induced cognitive deficits. Herein, we describe approaches to generate MGE-like progenitor cells from mouse embryonic stem (ES) cells. Using a modified embryoid body method, we provided gene expression evidence that mouse ES-derived Lhx6+ cells closely resemble immature interneurons generated from authentic MGE-derived Lhx6+ cells. We hypothesized that enhancers that are active in the mouse MGE would be useful tools in detecting when ES cells differentiate into MGE cells. Here we demonstrate the utility of enhancer elements [422 (DlxI12b), Lhx6, 692, 1056, and 1538] as tools to mark MGE-like cells in ES cell differentiation experiments. We found that enhancers DlxI12b, 692, and 1538 are active in Lhx6-GFP+ cells, while enhancer 1056 is active in Olig2+ cells. These data demonstrate unique techniques to follow and purify MGE-like derivatives from ES cells, including GABAergic cortical interneurons and oligodendrocytes, for use in stem cell-based therapeutic assays and treatments.

Original languageEnglish
Article numbere61956
JournalPloS one
Volume8
Issue number5
DOIs
Publication statusPublished - 01-05-2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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