Masse, Karine, Bhamra, Surinder, Eason, Robert, Dale, Nicholas and Jones, Elizabeth A. (2007) Purine-mediated signalling triggers eye development. Nature, Vol.449 (No.7165). pp. 1058-1062. ISSN 0028-0836

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Abstract

A conserved network of eye field transcription factors (EFTFs) underlies the development of the eye in vertebrates and invertebrates(1). To direct eye development, Pax6, a key gene in this network(2,3), interacts with genes encoding other EFTFs such as Rx1 and Six3 (refs 4-6). However, the mechanisms that control expression of the EFTFs remain unclear(7). Here we show that purine-mediated signalling triggers both EFTF expression and eye development in Xenopus laevis. Overexpression of ectonucleoside triphosphate diphosphohydrolase 2 (E-NTPDase2)(8), an ectoenzyme that converts ATP to ADP(9), caused ectopic eye-like structures, with occasional complete duplication of the eye, and increased expression of Pax6, Rx1 and Six3. In contrast, down-regulation of endogenous E-NTPDase2 decreased Rx1 and Pax6 expression. E-NTPDase2 therefore acts upstream of these EFTFs. To test whether ADP (the product of E-NTPDase2) might act to trigger eye development through P2Y1 receptors, selective in Xenopus for ADP(10,11), we simultaneously knocked down expression of the genes encoding E-NTPDase2 and the P2Y1 receptor. This could prevent the expression of Rx1 and Pax6 and eye formation completely. We next measured ATP release(12-14) in the presumptive eye field, demonstrating a transient release of ATP at a time that could plausibly trigger (once converted to ADP) expression of the EFTFs. This surprising role for transient purine-mediated signalling in eye development may be widely conserved, because alterations to the locus of E-NTPDase2 on human chromosome 9 cause severe head and eye defects, including microphthalmia(15-18). Our results suggest a new mechanism for the initiation of eye development.

Item Type:	Journal Item
Subjects:	Q Science
Divisions:	Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Journal or Publication Title:	Nature
Publisher:	Nature Publishing Group
ISSN:	0028-0836
Official Date:	25 October 2007
Volume:	Vol.449
Number:	No.7165
Number of Pages:	6
Page Range:	pp. 1058-1062
Identification Number:	10.1038/nature06189
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/31341

Data sourced from Thomson Reuters' Web of Knowledge

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