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. 2015 Sep 16;35(37):12869–12889. doi: 10.1523/JNEUROSCI.1164-15.2015

Figure 1.

Figure 1.

CGE-derived but not MGE-derived GABAergic cortical interneurons maintain expression of the transcription factor Prox1 during their development. A, B, Immunohistochemistry for Prox1 reveals expression within the SVZs of the ventral eminences (MGE, LGE, and CGE) as early as E10.5. Expression of Nkx2-1 largely demarcates the MGE domain. DAPI nuclear counterstain is shown in white. C, D, GABAergic neuronal precursors in the forebrain are labeled by EGFP through combinatorial use of a Dlx5/6-Flpe driver and an RCE:FRT reporter at E14.5. High levels of Prox1 expression are found in the SVZs of the MGE and CGE. Some non-GABAergic populations in the ventral forebrain also express Prox1 (open arrowheads). D′, A higher magnification picture of the neocortex in D is shown. Most Prox1-expressing cells are found to be GABAergic in the cortical plate (CP), intermediate zone (IZ), and subventricular/ventricular zones (SVZ/VZ). Non-GABAergic Prox1-expressing cells (red without green) within the marginal zone (MZ) are Cajal–Retzius cells and Prox1 expression within this population shuts off by E18.5 (confirmed by Wnt3a-Cre driver fate mapping; data not shown). E, E′, At E16.5, Prox1 expression is largely confined to GABAergic neuronal precursors within the cortex (E) and overlaps with Sp8 (E′). F, G, MGE-derived GABAergic populations are labeled with EGFP in Lhx6BAC-Cre; Dlx5/6-Flpe; RCE:dual animals. MGE-derived cortical interneuron precursors at E16.5 do not express Prox1 (F, F′). At P21, Prox1 remains absent from MGE-derived interneurons (G–G″). H–J, Analysis of Prox1 expression in specific CGE-derived cortical interneuron subtypes in Dlx6a-Cre; Prox1-C:EGFP/+ P21 brains. H, RELN-expressing interneurons that are negative for SST originate from the embryonic CGE and Prox1 expression (EGFP) are observed in 84.3% of this population albeit at variable levels (arrowheads; open arrowhead indicates Prox1-negative RELN-positive cell). SST-positive cells do not express Prox1 (asterisk). I, J, The majority of CR(Calb2)/VIP (double arrowheads) and VIP-single (single arrowhead) populations express Prox1. Most CR-positive cells lacking VIP are MGE derived (K) and do not express Prox1 (asterisk). K, A schematic correlating the molecular expression and the embryonic origin of GABAergic interneurons within the P21 mouse somatosensory barrel cortex (S1BF; adapted from Miyoshi et al., 2010). Prox1 is expressed within CGE-derived but not MGE-derived cortical interneuron subtypes. GP, globus paliidus; HC, hippocampus; Str, striatum; Th, thalamus. Scale bars: A–D, F, 200 μm; E–J, 50 μm.