Proceedings of The Physiological Society
King's College London (2011) Proc Physiol Soc 22, PC20
A bioinformatic and in situ screen for novel axon guidance molecules
S. Alsbury1, T. Okafuji2, S. O'Keeffe2, H. Karsten2, K. J. Mitchell2, G. Tear1
1. MRC Centre for Developmental Neurobiology, Kings College London, London, United Kingdom. 2. Smurfit Institute of Genetics, Trinity College, Dublin, Ireland.
Sophisticated genetic and biochemical screens for axon guidance molecules have identified a number of ligands and their axonal receptors. Many of these fall into a few major classes that share a limited number of structural motifs which are conserved from invertebrates to vertebrates. Although it has been speculated that the majority of axon guidance molecules have been discovered it is unlikely that sufficient molecules have been identified to encode the complete wiring of the embryonic nervous system. In order to identify further axon guidance molecules we have taken a systematic bioinformatic approach to identify novel transmembrane proteins that contain any of a number of conserved extracellular protein domains found in known axon guidance molecules. This screen has identified 158 genes in Drosophila that fulfil these criteria and their expression patterns were subsequently determined by in situ hybridization. This study yielded 46 candidates that show neural expression in the embryo during the period of axon extension. These include 8 genes that have orthologues in vertebrates including the CG32635/Neto and Ten/Odz families, Gogo and CG8403/Pikachurin. Pikachurin is a type II transmembrane receptor-like protein with predicted EGF and laminin domains. It has been identified to interact with dystroglycan and have a role in positioning the bipolar cell dendrites in the mouse photoreceptor ribbon synapse (Sato et al 2008). Drosophila Pikachurin is widely expressed in the embryonic nervous system. A small deletion in pikachurin created by imprecise excision of an existing P-element reveals a likely role in the targeting of the ISNb motor neurons.
Where applicable, experiments conform with Society ethical requirements