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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.

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