The Selleck laboratory is interested in how growth factor signaling shapes the development and function of the nervous system. These studies range from exploring the molecular determinants of signaling molecule gradients to the genetics of behavioral disorders in children. Their principal model system is the fruitfly, Drosophila melanogaster, which provides a wide array of powerful genetic, molecular and cellular methods to understand gene function. In addition to providing a system to identify novel genes affecting nervous system assembly, they employ Drosophila to understand the function of candidate disease genes identified from human genetic studies.
A principal effort in the lab is to understand how heparan sulfate proteoglycans, an abundant class of cell surface and matrix molecules, affect nervous system patterning and assembly. Initial studies demonstrated that a GPI-linked heparan sulfate proteoglycan encoded by division abnormally delayed (dally) was responsible for controlling cell cycle progression and growth factor signaling in the visual system (Nakato et al. 1995; Jackson et al. 1997). More recent work has established that glypicans pattern the nervous system by both controlling cell responses to Wnt and BMP-related ligands as well as dictating the levels of these signaling molecules in the matrix (Tsuda et al. 1999; Fujise et al. 2001; Kirkpatrick et al. 2004). The lab has also discovered that two distinct Drosophila HSPGs, a glypican and a syndecan, are expressed at high levels on axons and play distinct roles in axon guidance in the Drosophila visual system (Rawson et al. 2005).
The neuromuscular junction in Drosophila has provided a system to understand the molecular control of synapse development and plasticity. The Selleck lab was one of several groups to demonstrate that BMP signaling is essential for normal NMJ assembly and physiological function (Rawson et al. 2003). Current work examines the requirements for HSPGs in synapse assembly and function.
The lab’s recent human genetic studies were initiated by the identification of a large kindred with autism and developmental delay through the University of Minnesota clinics. They have identified a region of chromosome 10 susceptible to rearrangements that can contribute to abnormal behavioral development in children. Their studies now include detailed genomic and genetic mapping of chromosome 10 contributions to autism and the analysis of candidate genes using Drosophila.
Other studies in the lab examine the function of HSPGs in vascular and blood development using the zebrafish, Danio rerio, in collaboration with Dr. Steve Ekker (Chen et al. 2005).