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. 2010 Nov 24;30(47):16053–16064. doi: 10.1523/JNEUROSCI.4508-10.2010

Figure 3.

Figure 3.

PCP mutant mice display specific axon guidance and cell body orientation defects in the 5-HT system. A–L, Whole-mount 5-HT immunostaining. Ascending 5-HT populations are depicted in A–C, and descending 5-HT axons are shown in D–L. This is schematized in M. A, In E12.5 wild-type (WT) embryos, axons in the ascending 5-HT population emanate from the floor plate (FP) and strictly grow anterior toward the brain (arrows). In contrast, Fzd3−/− (B) or Lp/Lp (C) mice display ascending axons that grow laterally and posteriorly (arrows). Lp/Lp mice display many “wavy” axons characteristic of axons lacking appropriate guidance. D, In wild-type mice, descending axons project posteriorly toward the spinal cord at E12.5 (arrows). Both Fzd3−/− (E) and Lp/Lp (F, G) mice display aberrant descending projections (arrows). Fzd3−/− mice form very short axons within the descending region, many of which project into inappropriate lateral and anterior directions (E). G, Lp/Lp mice form axons within the descending region that display clear fasciculation defects and grow in large circles. Cell body orientation is also affected in Fzd3−/− mice. Although during their mediolateral migration most wild-type descending neurons display cell bodies oriented first laterally (en route to their final position) and then along the A–P axis as they reach their final lateral position (H–J), cell bodies in Fzd3−/− mice are oriented in several different directions, many projecting at an acute angle near the midline and failing to orient posteriorly as they reach their lateral resting position (K, L). The cell orientation phenotype is schematized in N and O and quantified in P. Graph shows average ± SEM. Almost 50% of Fzd3+/+ mice are oriented at 180° compared with Fzd3−/− mice in which only ∼10% of neurons are oriented posteriorly. M, Medial; L, lateral. Scale bars: A–C, 50 μm; D–G, 20 μm. *p < 0.05, **p < 0.01. Number of mutants analyzed: Fzd3−/−; n = 3 for E11.5, n = 15 for E12.5; n = 2 for E13.5; Celsr3−/−, n = 3 for E11.5; n = 4 for E12.5; Lp/Lp, n = 4 for E12.5.