In this pk1b-morphant environment, the vast majority of mutant neurons failed to migrate out of r4 (84% for nhsl1b, 91% for scrib, 97% for vangl2; Fig. 6E,G,I).
We reasoned that if nhsl1b, vangl2 or scrib mutant FBM neurons fail to migrate in pk1b-depleted hosts, this would mean that the rescue of their migration that we observed in a wild-type environment was mediated by the host FBM neurons themselves.
In FBM neuron migration, previous chimeric analyses have suggested that the PCP components Vangl2, Fzd3a and Celsr2 act primarily non cell-autonomously, as wild-type neurons fail to migrate through a mutant neuroepithelium and mutant neurons do migrate through a wild-type environment, albeit incompletely (Jessen et al., 2002; Wada et al., 2005; Wada et al., 2006).
For example, in pdm null mutants, cas expression is delayed [ 3] and U5 motor neurons fail to form [ 24].
(C ) VGlut2 (green) expressing neurons fail to form dorsomedial to VII in E18.5 Dbx1 LacZ/LacZ mutant mice.
(B ) RTN Lbx1 (red) and LacZ (green) co-expressing neurons fail to property migrate ventral to Isl1 expressing VII neurons in E18.5 Phox2b -Cre; Atoh1 LacZ/F (RL+/RTN−) mutant mice.
In Fezf1-deficient mice, olfactory neurons fail to mature and also express markers of functional VNO neurons.
Without Tbr1, neurons fail to migrate properly.
Notably, restriction of SOD1 mutant expression selectively to post-natal motor neurons failed to produce detectable sign of pathology or motor-neuron disease [ 29], suggesting that other cell types may be involved in ALS-associated neurodegeneration.
Regulation of microtubules by Sec8 might also explain why expression of a sec8 transgene in sec8 mutant neurons (elav C155 gal4/UAS-sec8; sec8) fails to rescue the synaptic overgrowth (Data not shown), and why overexpression of a sec8 transgene in sec8 mutant muscle (UAS-sec8; 24B gal4 or UAS-sec8; H94 gal4) fails to reverse sec8 mutant receptor trafficking phenotypes (Data not shown).
