Glia and barrier development
Our research program investigates the roles that glia play in the development and function of the nervous system. Glia are known to fulfill a number of important functions during nervous system development. Glia help guide axon guidance, separate axons bundles in nerves and finally wrap and insulate their associated axons and nerves. However many of the molecules and signals that mediate these roles of glia have yet to be determined. This is important given the essential role that glia play in the nervous systems of all animals. Any mutation or disease that disrupts glial cell function or development results in disruption of nervous system function and can lead to paralysis or death of the animal.
One approach to study molecular and cellular interactions that occur between glia and neurons during development is to use a genetic approach. The organism of choice for these studies is the fruit-fly, Drosophila melanogaster, because of the powerful genetic tools that can be applied to study the molecular interactions that occur during nervous system development. There are many parallels between the glia in of vertebrates and Drosophila and we have shown that many of the same molecular cues are conserved. For instance, we have shown that the glia of the peripheral nervous system in Drosophila are strikingly similar to the vertebrate peripheral glia (Schwann cells) in terms of morphology, developmental dynamics and molecular composition. We have shown that disruptions in the glia of the peripheral nervous system can lead to loss of nervous system function, neurodegeneration and death in Drosophila.
There are a number of related projects in the laboratory which correspond to the different stages of glial cell development.
Glial cell migration:
What molecular signals and cellular contacts drive glial cell migration?
Glial cell ensheathement/wrapping:
What molecular signals trigger the end of migration and the formation of the blood-nerve barrier?
Gliotactin and its role in glia and epithelia:
What molecular interactions mediate Gliotactin function in forming the junctions that underlie the Drosophila permeability barrier?
Schulte J, Charish K, Que J, Ravn S, Mackinnon C, Auld VJ. (2006) Gliotactin and Discs large form a protein complex at the tricellular junction of polarized epithelial cells in Drosophila. J Cell Sci. 119(21):4391-401 PMID: 17032735
Gilbert MM, Auld VJ. (2005) Evolution of clams (cholinesterase-like adhesion molecules): structure and function during development. Front Biosci. 10:2177-92. PMID: 15970486
Venema DR, Zeev-Ben-Mordehai T, Auld VJ (2004) Transient apical polarization of Gliotactin and Coracle is required for parallel alignment of wing hairs in Drosophila. Dev Biol. 275(2):301-14. PMID: 15501220
Schulte J, Tepass U, and Auld VJ. (2003) Gliotactin, a novel marker of tricellular junctions, is necessary for septate junction development in Drosophila. J Cell Biol. 161(5):991-1000. PMID: 12782681
Sepp KJ and Auld VJ (2003) Reciprocal interactions between neurons and glia are required for Drosophila peripheral nervous system development. J Neurosci. 23(23):8221-30. PMID: 12967983
Sepp KJ, and Auld VJ. (2003) RhoA and Rac1 GTPases mediate the dynamic rearrangement of actin in peripheral glia. Development 130(9):1825-35. PMID: 12642488
Sepp KJ, Schulte J, and Auld VJ. (2001) Peripheral glia direct axon guidance across the CNS/PNS transition zone. Dev. Biol. 238(1):47-63. PMID: 11783993
Gilbert M, Smith J, Roskams AJ, and Auld VJ. (2001) Neuroligin 3 is a vertebrate gliotactin expressed in the olfactory ensheathing glia, a growth-promoting class of macroglia. Glia 34(3):151-64. PMID: 11329178
Sepp KJ, Schulte J, and Auld VJ. (2000) Developmental dynamics of peripheral glia in Drosophila melanogaster. Glia 30(2):122-33. PMID: 10719354 Auld VJ. (1999)
Glia as mediators of growth cone guidance: studies from insect nervous systems. Cell Mol Life Sci. 55(11):1377-85. Review. PMID: 10518987
Sepp KJ and Auld VJ. (1999) Conversion of lacZ enhancer trap lines to GAL4 lines using targeted transposition in Drosophila melanogaster. Genetics 151(3):1093-101. PMID: 10049925
Auld VJ, Fetter RD, Broadie K, and Goodman CS. (1995) Gliotactin, a novel transmembrane protein on peripheral glia, is required to form the blood-nerve barrier in Drosophila. Cell 81(5):757-67. PMID: 7539719
Lin DM, Auld VJ, and Goodman CS. (1995) Targeted neuronal cell ablation in the Drosophila embryo: pathfinding by follower growth cones in the absence of pioneers. Neuron 14(4):707-15. PMID: 77182345
Lectures BIOL445 and BIOL350.