Editors' ChoiceDevelopment

Need ADP to See

Science's STKE  30 Oct 2007:
Vol. 2007, Issue 410, pp. tw393
DOI: 10.1126/stke.4102007tw393

Ectonucleoside triphosphate diphosphohydrolase 2 (E-NTPDase2) is a membrane-bound ectoenzyme that converts adenosine triphosphate (ATP) into adenosine diphosphate (ADP). In investigating roles for E-NTPDase2 in development, Massé et al. injected E-NTPDase2 mRNA into one side of a developing Xenopus laevis embryo and found ectopic eyelike structures on the injected side that were histologically characteristic of normal eyes. Pax6, Rx1, and Six3 encode eye-field transcription factors (EFTFs) that are responsible for eye development. Using in situ hybridization, the authors found that overexpression of E-NTPDase2 in injected embryos increased the expression of these EFTF genes. Knockdown of E-NTPDase2 by injection with a specific antisense morpholino oligonucleotide (MO) resulted in reduced expression of Pax6 compared with that in control MO-injected embryos, and knockdown of the ADP receptor P2Y1 had a synergistic effect on EFTF gene expression. Knockdown of both E-NTPDase2 and P2Y1 resulted in embryos with very small eyes, or even lacking an eye, on the injected side. Using a biosensor for ATP, transient production of ATP was detected in the anterior, but not posterior, neural plate at a time consistent with eye-field development; however, the cells responsible for releasing the ATP remain unknown. A P2Y1 antagonist blocked the effects of overexpression of E-NTPDase2, and a P2Y1 agonist rescued the effects of injection of an E-NTPDase2 MO. In humans, mutations in chromosome 9, where the gene locus of E-NTPDase2 is located, are associated with eye defects such as microphthalmia. This study suggests a mechanism whereby ADP signaling initiates development of the eye.

K. Massé, S. Bhamra, R. Eason, N. Dale, E. A. Jones, Purine-mediated signalling triggers eye development. Nature 449, 1058-1062 (2007). [PubMed]