Project description:During development, newborn interneurons migrate throughout the embryonic brain. Here, we provide evidence that these interneurons act in a paracrine fashion to regulate developmental oligodendrocyte formation. Specifically, we show that medial ganglionic eminence (MGE) interneurons secrete factors that promote genesis of oligodendrocytes from glially-biased cortical precursors in culture. Moreover, when MGE interneurons are genetically ablated in vivo prior to their migration, this causes a deficit in cortical oligodendrogenesis. Modeling of the interneuron-precursor paracrine interaction using transcriptome data identifies the cytokine fractalkine as responsible for the pro-oligodendrocyte effect in culture. This paracrine interaction is important in vivo, since knockdown of the fractalkine receptor CX3CR1 in embryonic cortical precursors, or constitutive knockout of CX3CR1 causes decreased numbers of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes in the postnatal cortex. Thus, in addition to their role in regulating neuronal excitability, interneurons act in a paracrine fashion to promote the developmental genesis of oligodendrocytes. We used microarrays to generate a list of expressed genes in purified medial ganglionic eminence (MGE) interneurons
Project description:There was a remarkable similarity in the molecular properties of the MGE-GFP+ and ES-GFP+ cells. In particular, genes that are important for medial ganglionic eminence (MGE) and cortical interneurons development are both high in expression in both MGE-Lhx6-GFP+ and ES-Lhx6-GFP+ cells (compared to ES-Lhx6-GFP- cells).
Project description:This study aimed to understand the role of the transcriptional regulator Prdm16 in the development of cortical interneurons in the mouse. Prdm16 was knocked out in cells derived from the medial ganglionic eminence (MGE) by using an Nkx2.1-Cre driver line in combination with a line carrying floxed Prdm16 alleles and with a Cre-dependent tdTomato reporter line (Ai14). The sequencing data compares the gene expression profiles of dissected MGEs at embryonic day 14 (E14), a stage when cortical interneurons are being generated from MGE progenitors.
Project description:Gene expression profiling of the medial (MGE), lateral (LGE) and caudal (CGE) ganglionic eminence, and cerebral cortex (CTX) at various embryonic stages (E12.5, E14 and E16).
Project description:Deep transcriptional profiling of the human neocortex, lateral ganglionic eminence (LGE) and medial ganglionic eminences (MGE), from 7 to 20 post-conceptional weeks (pcw), for de novo lincRNAs discovery and to establish a unique coding and non-coding gene signature for the three different regions.
Project description:We have used our protocol for generating cortical interneurons from human embryonic stem cells to study chromatin state changes during cortical interneuron development. This allows for the identification of cis-regulatory elements and transcription factors which play important roles in this process. Samples were collected at day 0 (hESCs), day 15 (ventral telencephalic patterned medial ganglionic eminence-like (MGE) progenitors), day 35 (immature interneurons), and day 60 (mature interneurons). Day 15 dorsal telencephalic cortical-like neural progenitors were also obtained by using a dual Smad inhibition protocol for comparison with ventral telencephalic MGE-like progenitors.
Project description:Cortical interneurons originating from the medial ganglionic eminence (MGE) are among the most diverse cells within the CNS. Different pools of proliferating progenitor cells are thought to exist in the ventricular zone of the MGE, but whether the underlying subventricular and mantle regions of the MGE are spatially patterned has not yet been addressed. Here, we combined laser-capture microdissection and multiplex RNA-sequencing to map the transcriptome of MGE cells at a spatial resolution of 50 M-BM-5m. Distinct groups of progenitor cells showing different stages of interneuron maturation were identified and topographically mapped based on their genome-wide transcriptional pattern. One 50 M-BM-5m coronal section from the MGE was taken from each of two wildtype and one GFRa1 mutant E12.5 C57bl6/J mouse. Each section was laser microdissected into approximately 100 cubes, covering the whole MGE, and each cube was further processed for RNA-seq analysis.
Project description:There was a remarkable similarity in the molecular properties of the MGE-GFP+ and ES-GFP+ cells. In particular, genes that are important for medial ganglionic eminence (MGE) and cortical interneurons development are both high in expression in both MGE-Lhx6-GFP+ and ES-Lhx6-GFP+ cells (compared to ES-Lhx6-GFP- cells). To investigate how closely ES cells-derived Lhx6-GFP+ cells resembled authentic Lhx6+ MGE cells, and to define the molecular properties of the Lhx6-GFP+ and Lhx6-GFP- cells from differentiated ES cells, we compared their gene expression profiles. We used FACS to purify GFP+ cells from the E12.5 MGE of Lhx6-GFP transgenic mice. ES-Lhx6-GFP+ cells and ES-Lhx6-GFP- cells (both from D12 EB aggregates) were also isolated by fluorescent activated cell sorting (FACS) and all of the RNA samples were subjected to RNA expression microarray analyses.
Project description:In the mammalian cortex, about 60% of GABAergic interneurons, mainly including parvalbumin-expressing (PV+) and somatostatin (SST+) interneurons are generated from the medial ganglionic eminence (MGE) in the subpallium and tangentially migrate to the cortex. Here we analyze the role of the Sp9 transcription factor in regulating the development of MGE-derived cortical interneurons. We show that SP9 is widely expressed in the MGE subventricular zone (SVZ) and in MGE-derived migrating interneurons. By analyzing Sp9 null and conditional mutant mice, we demonstrate that Sp9 promotes MGE progenitor proliferation in the SVZ and is required for the normal patterning of tangential migration and the laminar distribution of MGE-derived cortical GABAergic interneurons. Loss of Sp9 function results in a ~50% reduction of MGE-derived cortical interneurons, an ectopic aggregation of MGE-derived neurons in the embryonic ventral telencephalon, and an increased ratio of SST+/PV+ cortical interneurons. Finally, we provide evidence that Sp9 regulates MGE derived cortical interneuron development through promoting expression of the Lhx6 and Lhx8 transcription factors.
