Fig. 3. Abnormal migration of r4-derived motoneurons in Hoxa1, Hoxb1 and Hoxb2 mutant hindbrains. (A-D) Time course of Isl1 expression in wild-type flat-mounted hindbrains between 10.5 and 11.5 dpc (ventricular view). Expression was detected in the ventral domain of all rhombomeres, except rhombomere 1, and was strongest in r2 and r4, corresponding to the precursors of the trigeminal (Vm) and facial (VIIm) motoneurons, respectively. At 11.25 dpc, dorsal migration of the Vm and caudal migration of the VIIm began (C, black arrowheads) and continued until 11.5 dpc (D, black arrowheads) when Vm reached their final dorsal position. (E-H) Motoneuron distribution at 11.25 dpc in wild-type (E), Hoxa1 (F), Hoxb1 (G) and Hoxb2 (H) mutant flat-mounted hindbrains (ventricular view). The caudally migrating VIIm population was strongly reduced in Hoxa1 mutants (F, black arrowheads), absent in Hoxb1 mutants and depleted in Hoxb2 mutants (H, black arrowheads). The loss of the caudally migrating VIIm in the Hoxb1 mutants unmasks the abducens motoneurons (VIm) (G, black arrowheads). Note the presence of ectopic motor nuclei in r4 in all three mutants (F-H asterisks). (I-P) Ventricular (I-L) and pial (M-P) views of motoneuron distribution at 12.5 dpc in wild-type (I, M), Hoxa1 (J, N), Hoxb1 (K, O) and Hoxb2 (L, P) mutant flat-mounted hindbrains. At this stage, VIIm normally started migrating caudally and dorsally reaching the pial side of the hindbrain (I, M, black arrowheads). In the Hoxa1 mutants, caudal migration was sparse and no VIIm had reached the pial side at this stage (N, white arrowheads). Some migrating motoneurons turned dorsally prematurely (J, black arrowheads). In the Hoxb1 mutants, VIIm did not follow the normal migratory pathway (K,O, white arrowheads). This population was reduced in the Hoxb2 mutants. At this stage, all three mutants formed ectopic motor nuclei in r4 (J-K; asterisks in N-P). (Q-T) Ventricular views of the Isl1 expression pattern in flat-mounted Hoxb2 mutant hindbrains at 12.5 dpc. The VIIm population following the normal migratory pathway was variably reduced (black arrowheads). The ectopic nuclei were also variable (asterisks) in both their density and AP position.

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