Impeded Interaction between Schwann Cells and Axons in the Absence of Laminin α4

• DOI: 10.1523/jneurosci.5225-04.2005
• Publication Date: 2005-04-06T19:43:18Z
• Authors: Wilhelm Wallquist; Stefan Plantman; Sebastian Thams; Jill Thyboll; Jarkko Kortesmaa; Jan Lännergren; Anna Domogatskaya; Sven Ove Ögren; Mårten Risling; Henrik Hammarberg; Karl Tryggvason; Staffan Cullheim
• Keywords: Central Nervous System; Mice, Knockout; 0303 health sciences; Behavior, Animal; S100 Proteins; In Vitro Techniques; Immunohistochemistry; Sciatic Nerve; Axons; Nerve Regeneration; Mice; 03 medical and health sciences; Animals, Newborn; Microscopy, Electron, Transmission; Cell Movement; Muscle Spasticity; Animals; Laminin; Schwann Cells; Sciatic Neuropathy; Cells, Cultured; Demyelinating Diseases

The Schwann cell basal lamina (BL) is required for normal myelination. Loss or mutations of BL constituents, such as laminin-2 (α2β1γ1), lead to severe neuropathic diseases affecting peripheral nerves. The function of the second known laminin present in Schwann cell BL, laminin-8 (α4β1γ1), is so far unknown. Here we show that absence of the laminin α4 chain, which distinguishes laminin-8 from laminin-2, leads to a disturbance in radial sorting, impaired myelination, and signs of ataxia and proprioceptive disturbances, whereas the axonal regenerative capacity is not influenced.In vitrostudies show poor axon growth of spinal motoneurons on laminin-8, whereas it is extensive on laminin-2. Schwann cells, however, extend longer processes on laminin-8 than on laminin-2, and, in contrast to the interaction with laminin-2, solely use the integrin receptor α6β1 in their interaction with laminin-8. Thus, laminin-2 and laminin-8 have different critical functions in peripheral nerves, mediated by different integrin receptors.