Inhibition of col2a1 expression or crosslinking rescues polycystin axis curvature. Inhibition of col2a1 expression or crosslinking rescues polycystin axis.

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Volume 19, Issue 8, Pages (April 2009)

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Inhibition of col2a1 expression or crosslinking rescues polycystin axis curvature. Inhibition of col2a1 expression or crosslinking rescues polycystin axis curvature. (A–C) Wild-type embryo (A), pkd1a/b morphant (B), and pkd2 morphant (C) at 48 hpf. (D) col2a1 morphant at 48 hpf with slight ventral curvature. (E,F) col2a1 knockdown in pkd1a/b (E) and pkd2 (F) morphants relieves the dorsal axis curvature. (G) Wild-type 48 hpf embryo treated with 10 mM βAPN, a lysyl oxidase inhibitor, shows notochord distortion associated with a failure to generate a rigid, crosslinked notochord collagen sheath. Blocking collagen crosslinking relieves dorsal axis curvature in pkd1a/b (H) and pkd2 (I) morphants. (J–O) polycystin knockdown disrupts the feedback regulation of collagen gene expression. Embryos treated with 200 nM MCP and allowed to develop to 96 hpf (4 days) successfully repress col2a1 expression (J), but exhibit kinked notochords when stained with Alcian Blue (M). pkd2 (K) and pkd1a/b (L) morphants treated with 200 nM MCP fail to downregulate col2a1 expression in the notochord. (N,O) Histological sections of the embryos in K and L, respectively, confirm the aberrant notochord expression of col2a1. Bars, 10 μm (N,O). Steve Mangos et al. Dis. Model. Mech. 2010;3:354-365 ©2010 by The Company of Biologists Limited