Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis† †Electronic supplementary information (ESI) available: Figure showing the of effect of 5 and 6 on the notochord and experimental details for compounds 2–6. See DOI: 10.1039/b613673g Click here for additional data file.

نویسندگان

  • Carrie Anderson
  • Stephen J. Bartlett
  • John M. Gansner
  • Duncan Wilson
  • Ling He
  • Jonathan D. Gitlin
  • Robert N. Kelsh
  • James Dowden
چکیده

As a result of a chemical genetic screen for modulators of metalloprotease activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan mutant. The location of the chemically-induced wavy notochord correlated with the timing of application, thus defining a narrow chemical sensitivity window during segmentation stages. Microscopic observations revealed that notochord undulations appeared during the phase of notochord cell vacuolation and notochord elongation. Notochord cells become swollen as well as disorganized, while electron microscopy revealed disrupted organization of collagen fibrils in the surrounding sheath. We demonstrate by assay in zebrafish extracts that 2-mercaptopyridine-N-oxide inhibits lysyl oxidase. Thus, we provide insight into notochord morphogenesis and reveal novel compounds for lysyl oxidase inhibition. Taken together, these data underline the utility of small molecules for elucidating the dynamic mechanisms of early morphogenesis and provide a potential explanation for the recently established role of copper in zebrafish notochord formation.

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منابع مشابه

Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis{

As a result of a chemical genetic screen for modulators of metalloprotease activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan mutant. The location of the chemically-induced wavy notochord correlated with the timing of application, thus defining a narrow chemical sensitivity window during segmen...

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Laboratory of Molecular Recognition an Zhejiang University, Hangzhou 310027, Zh ac.cn State Key Laboratory of Organometallic C Chemistry, Chinese Academy of Sciences, [email protected] Shanghai Key Laboratory of Magnetic Reson Normal University, Shanghai 200062, P. R. † Electronic supplementary information ( and experimental procedures and theor 979559 and 990983. For ESI and crystallo format s...

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Institute for Materials Chemistry and Kasugakoen, Kasuga, Fukuoka 816-8580, Ja Department of Chemistry, Graduate Schoo Sendai 980-8578, Japan Institute for Materials Chemistry and En Fukuoka 819-0395, Japan CREST, Japan Science and Technology Fukuoka 816-8580, Japan † Electronic supplementary informati crystallographic, computational details, a 1057111–1057113 and 1425703. For ESI other electro...

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عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2007