Figure 9.

Ulk2 depletion is epistatic to Kctd12.1 mutation. A, B, Compared with normal Hb (A), neuropil development (white arrow) is slightly expanded in homozygous null kctd12.1 mutant animals [note absence of Kctd12.1 (green) in insets at right] (B). C, D, Reduced neuropil (yellow arrow) in the left Hb as a result of Ulk2 antisense depletion (C) also occurs (red arrow) when Ulk2 is depleted in a Kctd12.1 homozygous mutant, indicating that Ulk2 depletion is largely epistatic to mutation of Kctd12.1 (D). E, Volumetric quantification of Hb neuropil phenotype. Total neuropil volume is significantly reduced following injection of ulk2 MO^spl in either a wild-type or Kctd12.1 mutant background (asterisks indicate statistical difference compared with WT). Scale bar, 50 μm. *p < 0.05, **p < 0.01, two-tailed test. F, Model of proposed regulatory system resulting in asymmetric habenular neuropil extension. Ulk2 kinase acts bilaterally to promote elaboration of Hb neuropil but is negatively regulated by Kctd12 proteins. Asymmetry in neuropil arises from the greater relative potency of Kctd12.2 acting in medial subnuclei.