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.
- Ferguson, B. W., & Datta, S. (2011). Role of Heparan Sulfate 2-O-Sulfotransferase in Prostate Cancer Cell Proliferation, Invasion, and Growth Factor Signaling. Prostate Cancer. 2011, 1-14.
- Datta Kanjilal, S., & Datta, H. (2009). Subluxation of lens in Marfan syndrome.. Indian Pediatrics. 46(5), 434.
- Barrett, A. L., Krueger, S., & Datta, S. (2008). Branchless and Hedgehog operate in a positive feedback loop to regulate the initiation of neuroblast division in the Drosophila larval brain. DEVELOPMENTAL BIOLOGY. 317(1), 234-245.
- Barrett, A. L., Krueger, S., Jackson, M., & Datta, S. (2008). Curable genetic instability of a GAL4 transgene in Drosophila. FLY. 2(2), 67-73.
- Lindner, J. R., Hillman, P. R., Barrett, A. L., Jackson, M. C., Perry, T. L., Park, Y., & Datta, S. (2007). The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts. BMC Dev Biol. 7(1), 121-121.
- Lindner, Jonathan Ryan (2010-12). The Regulation of Growth Factor Signaling in Drosophila Development and Disease. (Doctoral Dissertation)
- Ferguson, Brent Wade (2010-12). Regulation of PERLECAN and 2OST Expression in Prostate Cancer Progression by Stress-activated Transcription Factors. (Doctoral Dissertation)
- Clarke, Douglas Nelson (2010-12). Perlecan Domain V Induces VEGF Secretion in Brain Endothelial Cells Through ?5?1 Integrin Dependent Mechanism a Novel Insight in Brain Tissue Recovery Following Ischemia. (Doctoral Dissertation)
- Hernandez, Ana Maria (2008-05). Perlecan regulation of sonic hedgehog signaling: from drosophila to humans. (Doctoral Dissertation)
- Barrett, Andrea Lynn (2007-12). A FGF-Hh feedback loop controls stem cell proliferation in the developing larval brain of drosophila melanogaster. (Doctoral Dissertation)