Laminin is required for Schwann cell morphogenesis

Abstract

Development of the peripheral nervous system requires radial axonal sorting by Schwann cells (SCs). To accomplish sorting, SCs must both proliferate and undergo morphogenetic changes such as process extension. Signaling studies reveal pathways that control either proliferation or morphogenesis, and laminin is essential for SC proliferation. However, it is not clear whether laminin is also required for SC morphogenesis. By using a novel time-lapse live-cell-imaging technique, we demonstrated that laminins are required for SCs to form a bipolar shape as well as for process extension. These morphological deficits are accompanied by alterations in signaling pathways. Phosphorylation of Schwannomin at serine 518 and activation of Rho GTPase Cdc42 and Rac1 were all significantly decreased in SCs lacking laminins. Inhibiting Rac1 and/or Cdc42 activities in cultured SCs attenuated laminin-induced myelination, whereas forced activation of Rac1 and/or Cdc42 in vivo improved sorting and hypomyelinating phenotypes in SCs lacking laminins. These findings indicate that laminins play a pivotal role in regulating SC cytoskeletal signaling. Coupled with previous results demonstrating that laminin is critical for SC proliferation, this work identifies laminin signaling as a central regulator coordinating the processes of proliferation and morphogenesis in radial axonal sorting.

Laminin regulates mouse embryonic stem cell migration: involvement of Epac1/Rap1 and Rac1/cdc42

“…Also, Yu et al (63) published that both activated Rac1 and cdc42 are greatly diminished in laminin-deficient Schwann cells, which suggest direct association between laminin and Rac1/cdc42. Our results indicated that laminin increased the protein level of Rac1/cdc42 in the plasma mem- Fig.…”

Basement Membranes: Cell Scaffoldings and Signaling Platforms

“…An evolving but incomplete model holds that laminin (or basement membrane) ligation of b1 integrins promotes lammellipodial extension and axonal interdigitation through alterations of the activated state of Rac1, Cdc42 and Rho/ Rho kinase. Laminins can affect both Schwann cell proliferation and process extension and proliferation whereas b1-integrins affect only the former (Yu et al 2005;Yu et al 2009). …”

Loss of focal adhesions in glia disrupts both glial and photoreceptor axon migration in the Drosophila visual system

“…During glial development, integrins are necessary for the radial sorting of axons and for subsequent myelination by oligodendrocytes and Schwann cells (Barros et al, 2009;Benninger et al, 2007;Camara et al, 2009;Feltri et al, 2002;Lee et al, 2006;Nodari et al, 2007;Yu et al, 2009). Similarly, loss of FAK or Integrin-linked kinase (ILK) mimics the phenotype of β1-integrin-deficient glia of both the PNS and CNS (Grove et al, 2007;Pereira et al, 2009).…”