Figure 2. Mef2c rescues the deficit of PV CIN production in cDKOs.

(A) Schema showing the MGE transplantation assay. RosaT⁺ or Maf^f/f;Mafb^f/f;RosaT⁺ MGE progenitors were dissected at E13.5, followed by transfection of Cre or Cre + Mef2c (expression vectors) to generate cDKO or cDKO + Mef2c MGE cells. We transplanted these cells into P1 WT neocortex and let them mature for 30 days before investigating CIN subtype markers. (B) Quantification of the proportion of transplanted WT, cDKO or cDKO with transfected Mef2c CINs that express either SST or PV. Note that the cDKO group recapitulated the phenotype of preferential loss of PV CINs; transfection with Mef2c rescued the production of PV CINs. Chi-square test was used for statistical analysis. (C–K) Representative singular cell images for group WT, cDKO and cDKO+Mef2c that are labeled with tdTomato and PV. Note that cDKO (F) has less complex neurite growing pattern compared to the WT (C). Also note the rescue of the PV expression in the cDKO+Mef2c (K) compared with the cDKO (H). Scale bar in (K) = 25 um. For SST IN comparison: WT-701 cells, cDKO-627 cells, cDKO+Mef2c- 304 cells; For PV IN comparison: WT- 670 cells, cDKO-587 cells, cDKO+Mef2c −236 cells. These numbers came from 6 WT animals, 4 cDKO animals and 3 cDKO + Mef2c animals. Cells analyzed were converted to contingency table to conduct Chi-square test. ****p<0.0001. Error bars represent standard errors of the mean.

Figure 2—figure supplement 1. Model.

(Left) Loss of Maf and Mafb in the MGE leads to overproduction of HINs (Sst⁺ and/or Pnoc⁺). (Right) DEX analysis revealed that at P0, Maf cDKOs have upregulated expression of Sst, Npy, Nrp1 and Pnoc; downregulated expression of Maf, Mafb, Mef2c, Cxcr4, Snap25, Nxph1 and Nxph2. Our data suggested that prenatally, Maf and Mafb promote Mef2c expression to drive PV IN production; postnatally, Maf and Mafb regulate Mef2c and Snap25 expression to regulate IN neurite morphogenesis.