Figure 5. Gfra1;Gfra2 double null mice phenocopy Ret mutants at E18.5.
(A–H) SC sections and whole mount L4/L5 DRGs of Tdt labeled RA mechanoreceptors from E18.5 Gfra1+/−;RetCreERT/+;RosaTdt control (A–B), Gfra1−/−;RetCreERT/+;RosaTdt mutant (C–D), Gfra1+/−; Gfra2GFP/+;RetCreERT/+;RosaTdt control (E–F) and Gfra1−/−; Gfra2GFP/GFP;RetCreERT/+;RosaTdt double null (G–H) embryos. (I) Quantification of Tdt+ pixels in dSC, which is displayed as a percentage normalized to dSC Tdt+ pixels of the within litter controls. (J) Quantification of number of Tdt+ DRG neurons per DRG, which is displayed as a percentage normalized to Tdt+ neurons of the within litter controls. Gfra1 mutants have no significant deficits in RA mechanosensory third order projections or cell survival at E18.5, indicating that ablating trans signaling alone is not sufficient to disrupt the development of RA mechanoreceptors. However, loss of both cis and trans signaling in Gfra1;Gfra2 double nulls leads to a significant loss of RA mechanosensory third order projection growth and cell number, suggesting that both cis and trans RET signaling contribute to the development of RA mechanoreceptors. Scale bars = 50 μm. Error bars represent SEM. n.s. = p > 0.05, *** = p < 0.001. Source data are provided in Figure 4—source data 1.