From Lgi4 to Adam22: Novel Players in Peripheral Nervous System Development and Myelination

Abstract

The evolution of complex nervous systems from simple sensory apparatuses in animals provides great advantages to these organisms. Not only does this facilitate their interactions with the outside world, but it also helps them to regulate homeostasis. Like all information transfer protocols, speed is a very important aspect of nerve impulse propagation. Neurons themselves are capable of very fast nerve conduction velocities, but myelination by glial cells gives a new meaning to the term conduction velocity as it cranks up the speed by two orders of magnitude. In the peripheral nerves of higher vertebrates, large calibre axons are myelinated by Schwann cells, whereas small calibre axons are supported by non-myelinating Schwann cells. Development and myelination of peripheral nerves involves the intimate association of neurons and glia, and the molecular cross-talk between axons and Schwann cells. Whereas several mechanisms both in the extra- and intracellular environments have been studied extensively, many unknowns governing the development and myelination of the peripheral nervous system remain. The main aim of this thesis is to identify and characterize such mechanisms, and the molecules involved. Throughout this project, we have worked with Claw paw, Lgi4, and Adam22 mutant mice. These animals display similar limb abnormalities, and hypomyelinated peripheral nerves. Combined efforts from our lab and our collaborators enabled us to characterize several aspects of these phenotypes, and to study the role of Lgi4 and Adam22 proteins.