Integrins are necessary for the development and maintenance of the glial layers in theDrosophilaperipheral nerve

Abstract

SUMMARYPeripheral nerve development involves multiple classes of glia that cooperate to form overlapping glial layers paired with the deposition of a surrounding extracellular matrix (ECM). The formation of this tubular structure protects the ensheathed axons from physical and pathogenic damage and from changes in the ionic environment. Integrins, a major family of ECM receptors, play a number of roles in the development of myelinating Schwann cells, one class of glia ensheathing the peripheral nerves of vertebrates. However, the identity and the role of the integrin complexes utilized by the other classes of peripheral nerve glia have not been determined in any animal. Here, we show that, in the peripheral nerves of Drosophila melanogaster, two integrin complexes (PS2PS and PS3PS) are expressed in the different glial layers and form adhesion complexes with integrin-linked kinase and Talin. Knockdown of the common beta subunit (PS) using inducible RNAi in all glial cells results in lethality and glial defects. Analysis of integrin complex function in specific glial layers showed that loss of PS in the outermost layer (the perineurial glia) results in a failure to wrap the nerve, a phenotype similar to that of Matrix metalloproteinase 2-mediated degradation of the ECM. Knockdown of PS integrin in the innermost wrapping glia causes a loss of glial processes around axons. Together, our data suggest that integrins are employed in different glial layers to mediate the development and maintenance of the protective glial sheath in Drosophila peripheral nerves.

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

“…1C-E). βPS was located in puncta, similar to those observed in the peripheral nerve (Xie and Auld, 2011), that were located at the interface of the PG layer and the ECM, the PG-CG interface, and between the two CG (Fig. 1D,E).…”

“…To analyze the roles of integrin in glia at larval stages, we used the pan-glial driver repo-GAL4 to drive the expression of RNAi constructs previously shown to knock down βPS and talin (Perkins et al, 2010;Xie and Auld, 2011). When repo-GAL4 drove the respective RNAi (repo>βPS-RNAi or repo>talin-RNAi), βPS or talin immunolabeling was absent in the OS glia, whereas the integrin complexes within the ED epithelia remained intact (supplementary material Fig.…”

ECM stiffness regulates glial migration in Drosophila and mammalian glioma models

“…In Drosophila, perineurial glial cells migrate below the neural lamella, a dense ECM surrounding the entire nervous system (Stork et al, 2008;Xie and Auld, 2011). We therefore set out to test whether modulation of ECM rigidity suppresses glial cell migration evoked by expression of activated PVR.…”

Kinesin Heavy Chain Function inDrosophilaGlial Cells Controls Neuronal Activity

“…Recently the role of focal adhesion kinase 56 ( fak56 ) in Drosophila nerves was reported (Ueda et al, 2008). Focal adhesion kinase acts downstream of integrin receptors, which are also known to be expressed by Drosophila glial cells (Murakami et al, 2007;Xie and Auld, 2011). Interestingly, loss of fak56 function in the subperineurial glial cells (which constitute the blood-brain barrier) lowers axonal conductance in larvae and also renders the larvae sluggish pointing toward the notion that adhesion is required for a full establishment of the blood-brain barrier (Ueda et al, 2008).…”