Figure 1.

In utero electroporation (EP) of Arx^WT, Arx^E or control constructs into Arx^-/Y;Pou3f4-cre+ (mutant) embryos compared with EP into wild-type littermates demonstrates that Arx^E has a partial ability to rescue radial cell migration in the mutant mice; in contrast, slice electroporation of Arx^E cannot rescue migration. (A) Wild-type embryos electroporated at E14.5 with a control vector expressing GFP were harvested at E18. Sections are counterstained with DAPI (blue). (B) An Arx^-/Y;Pou3f4-cre+ brain electroporated with a control construct shows a defect in radial migration. (C and D) Arx^-/Y; Pou3f4-cre+ embryos electroporated with Arx^WT (C) or Arx^E (D) show rescue of radial migration. Scale bar (upper right corner in A): 100 mm. (E) Normal NRCM is observed in E14.5 wild-type brains after EP of a control dsRed construct. White lines define the pial and ventricular surfaces. (F) In contrast, brains in which Arx is conditionally deleted in interneurons (Arx^-/Y;Dlx5/6^CIG) have loss of NRCM. Electroporation of Arx^WT (G) but not Arx^E (H) is able to partially rescue this migration defect. (E'–H') Detail of interneurons migrating in the pallium; the furthest-migrating interneuron is indicated with an arrow. Results were the same for Arx^-/Y;Pou3f4-cre slice culture. (I) Control electroporation in wild-type E12.5 slice culture. (J) Loss of migration in E12.5 Arx^-/Y;Pou3f4-cre slice culture. (K) NRCM rescue with Arx^WT at E12.5. (L) Failure of rescue by Arx^E at E12.5. A line drawn between the asterisks' define the location of the pallial–subpallial boundary (I–L, line not drawn so data are not obscured). (M) Counts in wild-type brains and both types of mutant brains electroporated with Arx^WT were significantly different from all others (n > 10 for each genotype-rescue combination; *, ^#P < 0.05). A trend toward rescue was observed with electroporation of Arx^WT but not Arx^E into mutant brains. (N) Quantification of NRCM after E12.5 rescue shows Arx^WT rescued NRCM at E12.5 (n > 7 for each genotype–rescue combination; *P < 0.05). No statistical differences were found between migration for Arx^-/Y;Dlx5/6^CIG and Arx^-/Y;Pou3f4-Cre+ mutant mice; quantification includes both mutant lines. Each genotype/construct combination is represented by at least three brains from three different litters of each mutant line at each time point. PSB, pallial-subpallial boundary; error bars, SEM; scale bar (in A): 500 mm.