Which alpha integrin pairs with betal to form the Schwann cell receptor required

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(Oral presentation from Antwerp Consortium July 2009)

Which alpha integrin pairs with betal to form the Schwann cell receptor required

for nerve development?

M. Pellegattat, A. D'Ursot, D. Zambronit, A. Nodari2 , A. De Arcangelis3 , E.

sLabouesse3, L. Wrabetzrand M.L. Feltrir

ISan Raffaele Scientific Institute, Milano, Italy; 'National Institutes of

Health (NIH), Bethesda, USA; 3Institut de Genetique et de Biologie MoIeculaire

et Cellulaire, Strasbourg, France

During peripheral nervous system development Schwann cells segregate large

caliber axons destined to be myelinated during the process of " axonal sorting " .

Axonal sorting is a prerequisite for myelination and requires signals deriving

from both axons and the extracellular matrix. Genetic alterations in mice have

shown that laminins and betal integrins are required in Schwann cells for axonal

sorting, Thus a receptor containing beta integrin links laminin to the Schwann

cell cytoskeleton to enable them to ensheathe axons. To form

laminin receptors, beta integrin can pair with different alpha integrin chains,

many of which are expressed by Schwann cells (alpha1, 2, 3, 6 and 7).

The goal of this study is to identify the partner of betal integrin in the

receptor involved in axonal sorting. Since alpha6 integrin

is highly expressed in Schwarm cells at the time of axonal sorting, we ablated

it specifically in these cells using the CrelLoxP system in mice. Surprisingly,

alpha6 conditional null mice are phenotipically normal and mutant sciatic nerves

and spinal roots do not present sorting abnormalities. We thus analyzed possible

compensatory expression of other alpha integrin subunits and we found an earlier

and higher expression of alpha7 integrin in developing

alpha6 null nerves. Thus we produced double alpha6/alpha7 null mice and found

morphological evidences of a defective radial sorting.

Further studies are necessary to understand the signalling mediated by

alpha6beta and alpha7betal integrins and the single

contribution of other alpha-beta laminin receptors in the process of radial

sorting.