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Figure 2 | Cell & Bioscience

Figure 2

From: Development and specification of GABAergic cortical interneurons

Figure 2

Specification of GABAergic Cortical Interneurons. With regard to the specification of MGE-derived interneuronal progenitors, several transcription factors play a role. Shh signaling activates Nk×2.1, which is the key transcription factor in specifying PV- and SST-positive interneurons from this region. Lh×6 and Lh×8 are transcription factors that lie downstream of Nk×2.1; they also aid in the specification of PV and SST interneurons (see text). Sox6 lies downstream of both Nkx2.1 and Lhx6/8. The Dlx homeobox family of genes play a key role in specification of CGE-derived cortical interneurons, although they also function to maintain the PV-expressing subset of MGE-derived interneurons (Dlx5 in particular). Arx is a homeobox transcription factor whose expression is directly affected by Dlx genes; Arx seems to play a role in the migration of interneurons to the cortex. Gsx1 and Gsx2 are both required for the specification of cortical interneurons that originate in the CGE. Mash1 is a downstream transcription factor whose absence results in reduced cortical interneuron numbers; it is required for proper function of the Notch ligand Delta1, which, in the Notch signaling pathway, serves to repress neuronal differentiation. The Dlx genes lie further downstream and play a crucial role in CGE-derived interneuron specification. The molecular mechanisms behind POA interneuron specification are unclear, although Nk×2.1 is expressed by interneurons derived from this area. Lh×6 is not expressed by these interneurons. Nk×5.1 was shown to affect the specification of NPY and Reelin interneurons.

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