Title:
Linx: a novel transmembrane protein directing the establishment of neural circuits during development

Kenji Mandai, M.D., Ph.D.
Division of Molecular and Cellular Biology
Kobe University Graduate School of Medicine

Abstract:
 The establishment of neural circuits relies on neural responses to guidance cues that are expressed spatially and temporally in a right place. To address molecular mechanisms underlying axonal growth, guidance, and target field innervation of developing neurons, we performed genome-wide screens [1, 2] and identified a novel gene, Linx [2]. Linx is a member of a LIG(leucine-rich repeat and immunoglobulin) gene family of transmembrane proteins. Linx and its family members are expressed in unique subsets of sensory and motor neurons where they physically interact with TrkA and Ret. Interestingly, Linx mutant mice display axonal projection defects, which resemble those found in mice lacking Ngf , TrkA and Ret . These findings show that Linx and its family members form complexes with receptor tyrosine kinases in unique populations of developing neurons and modulate their activities to control axonal growth, guidance and target field innervation. In this way, LIG gene family members provide fine-tuned control over neural circuit formation. In addition, we have recently found that Linx non-cell-autonomously regulates the development of large axon bundles in the brain. I will present our latest insights into molecular mechanisms of the establishment of neural circuits by Linx .

References:
1)Guo, T., Mandai, K., Condie, B.G., Wickramasinghe, S.R., Wang, F., Capecchi, M.R., and Ginty, D.D. (2011)
An evolving NGF-Hoxd1 signaling pathway mediates development of divergent neural circuits in vertebrates.
Nat Neurosci, 14, 31-36.

2)Mandai, K., Guo, T., St. Hillaire, C., Meabon, J.S., Kanning, K.C., Bothwell, M., and Ginty, D.D. (2009)
LIG family receptor tyrosine kinase-associated proteins modulate growth factor signals during neural development.
Neuron, 63, 614-627.