A time and a place for nkx2-1 in interneuron specification and migration

Abstract

The homeobox transcription factor, Nkx2-1, plays multiple roles during forebrain development. Using restricted genetic ablation of Nkx2-1, in this issue of Neuron, Butt et al. show that Nkx2-1 in telencephalic progenitors regulates interneuron subtype specification, while Nóbrega-Pereira et al. demonstrate that postmitotic Nkx2-1 regulates migration and sorting of interneurons to the striatum or cortex by controlling the expression of the guidance receptor, Neuropilin-2.

Figure 1

(A) (Left) Schematic of an E12.5 mouse brain highlighting the three major proliferative zones of the ventral telencephalon. Nkx2-1 expression defines the medial ganglionic eminence (MGE, blue). Dorsal to the MGE and separated by an anatomical sulcus is the lateral ganglionic eminence (LGE, red). Posterior to the end of the sulcus (arrowhead) where the MGE and LGE fuse is the caudal ganglionic eminence (CGE, orange). Nkx2-1 is also expressed in the septum and preoptic area (not shown). The straight line delineates the coronal slice shown in (B). (Right) Early and late removal of Nkx2-1 expression in MGE progenitors changes the fate of MGE-derived precursors in a temporally distinct manner such that they acquire LGE and CGE characteristics. See Butt et al. (2008) for details. (B) Schematic of a coronal section of a developing mouse brain highlighting the routes of migration for MGE-derived Nkx2-1-expressing interneurons. One stream of interneurons maintains expression of Nkx2-1 (blue) and migrates to the striatum while the other downregulates Nkx2-1 expression and migrates to the cortex. Nobrega-Pereira et al. (2008) show that Nkx2-1 expression underlies the sorting mechanism for cortical and striatal interneurons by repressing Neuropilin-2 receptor expression (Nrp2, green dots). Nkx2-1⁻/Npn2⁺ cells are repelled by the expression of Semaphorin-3A and -3F (Sema3A/F, red bars) in the striatum and migrate to the cortex.