Dlx1&2 and Mash1 transcription factors control MGE and CGE patterning and differentiation through parallel and overlapping pathways

Department of Psychiatry and the Nina Ireland Laboratory of Developmental Neurobiology, University of California at San Francisco, San Francisco, CA 94158-2324, USA.
Cerebral Cortex (Impact Factor: 8.67). 05/2009; 19 Suppl 1(Suppl. 1):i96-106. DOI: 10.1093/cercor/bhp045
Source: PubMed Central

ABSTRACT Here we define the expression of approximately 100 transcription factors (TFs) in progenitors and neurons of the developing mouse medial and caudal ganglionic eminences, anlage of the basal ganglia and pallial interneurons. We have begun to elucidate the transcriptional hierarchy of these genes with respect to the Dlx homeodomain genes, which are essential for differentiation of most gamma-aminobutyric acidergic projection neurons of the basal ganglia. This analysis identified Dlx-dependent and Dlx-independent pathways. The Dlx-independent pathway depends in part on the function of the Mash1 basic helix-loop-helix (b-HLH) TF. These analyses define core transcriptional components that differentially specify the identity and differentiation of the globus pallidus, basal telencephalon, and pallial interneurons.

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Available from: Gregory Brian Potter, Feb 18, 2014
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    • "The use of transcription factor expression to classify arkypallidal and prototypic neurons has relevance for understanding the developmental origins of these GPe cell types. Indeed, Nkx2-1 is expressed throughout the proliferative ventricular zone of the MGE in the embryonic subpallium/ventral telencephalon (Butt et al., 2005; Flames et al., 2007; Long et al., 2009; Nó brega-Pereira et al., 2010; Sussel et al., 1999), suggesting that the MGE is the progenitor domain of origin of most GPe neurons (Flandin et al., 2010; Nó brega-Pereira et al., 2010; Sussel et al., 1999). However, as much as one quarter of all GPe cells are generated outside the Nkx2-1+ MGE (Nó brega-Pereira et al., 2010). "
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    • "Dlx1/2-null mutants have a severe deficit in survival and migration resulting in a 70% reduction of these cells in the neocortex (Anderson et al., 1997; Sussel et al., 1999). Working in concert with Dlx1/2, the proneural gene Mash1 is expressed in the subpallial SVZ and is required for the production and differentiation of GABAergic interneurons (Casarosa et al., 1999; Petryniak et al., 2007; Long et al., 2009). Similar to Dlx1/2, elimination of Mash1 expression results in a substantial decrease in GABAergic neocortical interneurons (Casarosa et al., 1999). "
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    • "Loss-of-function mutations of Shh or Nkx2.1 lead to improper patterning of the ventral telencephalon and a lack of interneuron generation (Chiang et al., 1996; Sussel et al., 1999). Dlx1/2 knockout mice exhibit a defect in migration (Long et al., 2009). Mutations of the homeobox gene ARX in human subjects have demonstrated an interneuron migration defect and patients display autism and epilepsy. "
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