Figure 4. Hif1α Deletion Regulates GZ Exit.

(A) Hydroxylation-deficient Hif1α (Hif1 HD) expression impairs ex vivo CGN migration (41.7±3.6 μm $\left[\overline{\text{x}}\text{distance}\pm \text{sem}\right]$ vs. 58.2±4.0 μm in a LacZ controls [χ² test, P<0.0001, 48h t-test P<0.02]). Expressing Cre recombinase in Hif1α^flx/flx cerebella led to precocious migration in 20% O₂ (${\text{Cre}}^{\text{inactive}}:\overline{\text{x}}=33.9\pm 0.5\mu \text{m}$, ${\text{Cre}}^{\text{active}}:\overline{\text{x}}=48.1\pm 2.57\mu \text{m}$, P < 0.001) and rescued the 2% O₂ migration deficit (${\text{Cre}}^{\text{inactive}}:\overline{\text{x}}=25.3\pm 1.3\mu \text{m}$, ${\text{Cre}}^{\text{active}}:\overline{\text{x}}=43.5\pm 3.7\mu \text{m}$, χ² and t-test P < 0.0002). (B) Longitudinal time-lapse analysis of ex vivo migration kinetics in Hif1α^flx/flx CGNs transfected with Cre^inactive or Cre^active (see Fig. 3B for plot labels). Layer occupancy plots for Hif1α^flx/flx CGNs and Hif1α^−/− CGNs shows Hif1α^−/− CGNs leave the GZ early, but Hif1α^flx/flx CGNs quickly catch up (C) Expressing Cre recombinase in VHL^flx/flx cerebella reduced ex vivo CGN migration (${\text{Cre}}^{\text{inactive}}:\overline{\text{x}}=117.6\pm 0.4\mu \text{m}$, ${\text{Cre}}^{\text{active}}:\overline{\text{x}}=80.5\pm 3.8\mu \text{m}$, P < 0.0001 [χ² test] or P < 0.001 [t-test]), but was restored by VHL cDNA (${\text{Cre}}^{\text{active}}+\text{VHL}:\overline{\text{x}}=105.7\pm 4.7\mu \text{m}$; P < 0.0001 [χ² test] or P < 0.004 [t-test] vs Cre^active). (D) Longitudinal time-lapse analysis of ex vivo migration kinetics in VHL^flx/flx CGNs transfected with Cre^inactive or Cre^active (see Fig. 3B for plot labels). Percentage layer occupancy plots show VHL^−/− CGNs have delayed GZ exit compared to VHL^flx/flx CGNs.