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Hmgcrb and Fntb are required for FBMN migration. (A) Summary of the Hmgcrb biosynthetic pathway, including enzymes (green) and disrupting agents used in this study (red). Hmgcrb catalyzes the first rate-limiting step in the generation of farnesylated and geranylgeranylated proteins, as well as in the synthesis of cholesterol. (B-H) Maximum projection dorsal views of FBMNs (green) in 42 hpf Tg(islet1:GFP) zebrafish embryos, immunostained for EphA4 to mark r5 (red). FBMNs migrate to r6 in control embryos (B), whereas migration is completely blocked in Pk1b morphants (C). Disruption of Hmgcrb function in hmgcrb mutants (D), by injection of Hmgcrb MO (E) or by treatment with atorvastatin (F), partially blocks migration. Migration is also partially blocked in embryos injected with Fntβ MO (G) or with the Fnt inhibitor L-744 (H). Scale bar: 20 μm. (I) Extent of FBMN migration following the treatments indicated. The number of embryos scored is indicated in parentheses.
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