Seth Blair

Research Description:
Over the last decade we have learned a great deal about the processes that give rise to the various cell types of the adult wing of the fruitfly, allowing us to quickly link mutations that affect wing development to specific molecular processes. This, coupled with the unparalleled molecular and genetic tools available in Drosophila, make the wing a powerful system for isolating and analyzing novel genes. We have been using this system to identify new, critical regulators of developmental signaling pathways. We have two current areas of research. First, developmental signaling is often regulated, not by the localized expression of ligand or receptor, but by the expression of secreted ligand-binding modulators. Chordin is a famous vertebrate example that sequesters and inhibits BMP morphogens, helping ensure, amongst other things, that you have a nervous system. However, ligand-binding molecules can also stimulate signaling, and researchers are still trying to understand the mechanisms by which this happens. We have isolated several Drosophila proteins that increase the range and effectiveness of two critical developmental signals, the BMP and the Hedgehog family, and are examining their function using genetics and biochemical methods. Second, we have by examining a poorly understood signaling pathway by which two huge protocadherins, Fat and Dachsous regulates growth via the Hippo pathway, proximo-distal patterning and planar cell polarity in the wing. We have been examining the function of Fat’s intracellular domain, have isolated separate portions active in each of these pathways, and are using them to identify downstream targets. We have also been examining the pathway genetically by isolating novel regulators, such as the DHHC palmitoyltransferase Approximated.

Representative Publications:
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Serpe, M.*, Umulis, D.*, Ralston, A., Chen, J., Olson, D.J., Avanesov, A., Othmer, H., O’Connor, M.B. and Blair, S.S. (2008). The BMP binding protein Crossveinless 2 is a short-range, concentration -dependent, biphasic modulator of BMP signaling in Drosophila. Dev. Cell 14, 940-953.

Matakatsu, H. and Blair, S.S. (2008). The DHHC palmitoyltransferase Approximated regulates Fat signaling and Dachs subcellular localization and activity. Curr. Biol. 18, 1390-1395.

Umulis, D., O’Connor, M.B. and Blair, S.S. (2009). Extracellular regulation of bone morphogenetic protein signaling. Development 136, 3715-3728.

Avanesov, A., Honeyager, S.M., Malicki, M. and Blair, S.S. (2012). The role of glypicans in Wnt Inhibitory Factor 1 activity and the structural basis of Wif1’s effects on Wnt and Hedgehog signaling. PLOS Genetics Feb;8(2):e1002503.

Matakatsu, H. and Blair, S.S. (2012). Separating planar cell polarity and Hippo pathway activities of the protocadherin Fat. Development 139, 1498-1508.

Chen, J., Honeyager, S.M., Schleede, J., Avanesov, A, Laughon, A and Blair, S.S. (2012). Crossveinless d is a vitellogenin-like lipoprotein that binds BMPs and HSPGs and is required for BMP signaling in the Drosophila wing. Development 139, 2170-2176.