The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

Abstract

During development, the growth of the animal body is accompanied by a concomitant elongation of the peripheral nerves, which requires the elongation of integrated nerve fibers and the axons projecting therein. Although this process is of fundamental importance to almost all organisms of the animal kingdom, very little is known about the mechanisms regulating this process. Here, we describe the identification and characterization of novel mutant alleles of GlcAT-P, the Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P mutants reveal shorter larval peripheral nerves and an elongated ventral nerve cord (VNC). We show that GlcAT-P is expressed in a subset of neurons in the central brain hemispheres, in some motoneurons of the ventral nerve cord as well as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants the VNC is under tension of shorter peripheral nerves suggesting that the VNC elongates as a consequence of tension imparted by retarded peripheral nerve growth during larval development. We also provide evidence that for growth of peripheral nerve fibers GlcAT-P is critically required in hemocytes; however, glial cells are also important in this process. The glial specific repo gene acts as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P mutant background enhances VNC elongation. We propose a model in which hemocytes are required for aspects of glial cell biology which in turn affects the elongation of peripheral nerves during larval development. Our data also identifies GlcAT-P as a first candidate gene involved in growth of integrated peripheral nerves and therefore establishes Drosophila as an amenable in-vivo model system to study this process at the cellular and molecular level in more detail.

Tracing cells throughout development: insights into single glial cell differentiation

“…Pandey and colleagues also show that in brave mutants less glial cells are found along shortened nerves, again indicating that cell specific proliferation of perineurial cells is controlled by underlying peripheral nerves. 13 In contrast to these data, we observed the same amount of glial cells in tubby mutant larvae (which are about 30% shorter) compared with wild type animals of the same stage. We cannot interpret this discrepancy, nor do we know the underlying signals for both perineurial specific proliferation and subperineurial/wrapping glial cell growth.…”

Drosophila glia: Few cell types and many conserved functions

“…In the absence of the neural lamella, or loss of integrin mediated contact to this structure, the nervous system fails to be condensed in its normal form and rather stays in its original embryonic appearance. In addition, the lack of the neural lamella or its altered stiffness disrupts migration of the perineurial glia (Kim et al, ; Meyer, Schmidt, & Klämbt, ; Pandey, Blanco, & Udolph, ; Petley‐Ragan, Ardiel, Rankin, & Auld, ; Skeath et al, ; Tavares et al, ).…”

“…Color code is as in Figure 1. For further details see text (Kim et al, 2014;Meyer, Schmidt, & Klämbt, 2014;Pandey, Blanco, & Udolph, 2011;Petley-Ragan, Ardiel, Rankin, & Auld, 2016;Skeath et al, 2017;Tavares et al, 2015).…”

Over-expression of Hsp83 in grossly depletedhsrωlncRNA background causes synthetic lethality andl(2)glphenocopy inDrosophila

“…7A). Interaction between the neural lamella (extra-cellular lamella) and glia shapes the VG and either down-or up-regulation of its components results in elongated nerve cord phenotype (Kato et al 2011; Martinek et al 2008; Meyer et al 2014; Pandey et al 2011; Schmidt et al 2012; Xie and Auld 2011). Expressions of these genes were affected in Hsp90GFP as well as hsrω 66 but to a much less extent than in hsrω 66 Hsp90GFP larvae (Fig.…”