Conserved function of mSpry-2, a murine homolog of Drosophila sprouty, which negatively modulates respiratory organogenesis

In Drosophila embryos, the loss of sprouty gene function enhances branching of the respiratory system. Three human sprouty homologues (h-Spry1-3) have been cloned recently, but their function is as yet unknown ill, Here, we s how that a murine sprouty gene (mSpry-2), the product of which shares 97% h omology with the respective human protein, is expressed in the embryonic mu rine lung. We used an antisense oligonucleotide strategy to reduce expressi on of mSpry-2 by 96%, as measured by competitive reverse transcriptase PCR, in E11.5 murine embryonic lungs cultured for 4 days [2]. Morphologically, the decrease in mSpry-2 expression resulted in a 72% increase in embryonic murine lung branching morphogenesis as well as a significant increase in ex pression of the lung epithelial marker genes SP-C, SP-B and SP-A. These res ults support a striking conservation of function between the Drosophila and mammalian sprouty gene families to negatively modulate respiratory organog enesis.