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• W2075604741 endingPage "11088" @default.
• W2075604741 startingPage "11076" @default.
• W2075604741 abstract "Growing axons navigate a complex environment as they respond to attractive and repellent guidance cues. Axons can modulate their responses to cues through a G-protein-coupled, cAMP-dependent signaling pathway. To examine the role of G-protein signaling in axon guidance <i>in vivo</i>, we used the GAL4/UAS system to drive expression of dominant-negative heterotrimeric G-proteins (DNG) in retinal ganglion cells (RGCs) of embryonic zebrafish. Retinal axons normally cross at the ventral midline and project to the contralateral tectum. Expression of DNGα_S in RGCs causes retinal axons to misproject to the ipsilateral tectum. These errors resemble misprojections in <i>adcy1</i>, <i>adcy8</i>, <i>nrp1a</i>, <i>sema3D</i>, or <i>sema3E</i> morphant embryos, as well as in <i>sema3D</i> mutant embryos. <i>nrp1a</i> is expressed in RGCs as their axons extend toward and across the midline. <i>sema3D</i> and <i>sema3E</i> are expressed adjacent to the chiasm, suggesting that they facilitate retinal midline crossing. We demonstrate synergistic induction of ipsilateral misprojections between <i>adcy8</i> knockdown and transgenic DNGα_S expression, <i>adcy8</i> and <i>nrp1a</i> morphants, or <i>nrp1a</i> morphants and transgenic DNGα_S expression. Using qPCR analysis, we show that either transgenic DNGα_S-expressing embryos or <i>adcy8</i> morphant embryos have decreased levels of <i>nrp1a</i> and <i>nrp1b</i> mRNA. Ipsilateral misprojections in <i>adcy8</i> morphants are corrected by the expression of an <i>nrp1a</i> rescue construct expressed in RGCs. These findings are consistent with the idea that elevated cAMP levels promote Neuropilin1a expression in RGCs, increasing the sensitivity of retinal axons to Sema3D, Sema3E, or other neuropilin ligands at the midline, and consequently facilitate retinal axon crossing in the chiasm." @default.
• W2075604741 created "2016-06-24" @default.
• W2075604741 creator A5008165829 @default.
• W2075604741 creator A5011974068 @default.
• W2075604741 creator A5047794258 @default.
• W2075604741 creator A5064469673 @default.
• W2075604741 date "2013-07-03" @default.
• W2075604741 modified "2023-09-30" @default.
• W2075604741 title "cAMP-Induced Expression of Neuropilin1 Promotes Retinal Axon Crossing in the Zebrafish Optic Chiasm" @default.
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