SCHOLARS@TAMU

We are currently investigating how organismal level cues regulate the onset of stem cell division during development. Our primary system is the neuroblasts in the brain of the fruit fly, Drosophila melanogaster. The trol gene of Drosophila encodes the fly homolog of the mammalian heparan sulfate glycoprotein, Perlecan. Perlecan is found in mice, humans, and C. elegans, and is widely known as a co-receptor for the growth factor FGF. We have shown that Trol, the Drosophila Perlecan homolog, is required for signaling by FGF. Furthermore, we have demonstrated that Trol is also a likely candidate for the Hedgehog co-receptor. Hedgehogs are peptide growth factors which are conserved in mammals and require heparan sulfate glycoproteins for their movement and long-range signaling; however, until now the identity of the protein core was unknown. Our studies demonstrate genetic interactions between trol and hedgehog or patched mutations (patched is the Hedgehog receptor). Further studies reveal that both FGF and Hedgehog signaling activate stem cell division. Current projects involve determining how Trol stimulates FGF and Hedgehog signaling through genetic, molecular, and biochemical analyses.