Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila.

Sophie Cate,Thomas Raabe,Samantha Alsbury,Guy Tear,Kevin J Mitchell,Sangeetha Gajendra

doi:10.1242/dev.129684

Abstract

The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance.

Highlights

In the central nervous system (CNS) of vertebrates and invertebrates most neurons extend across the midline to form commissures, while the remainder extend on their own side (Tear, 1999; Kaprielian et al, 2001; Garbe and Bashaw, 2004; Evans and Bashaw, 2010)
This decision depends in part on the responsiveness of the growth cone to Netrin attractants and Slit repellents, both secreted from cells at the midline, additional mechanisms exist to direct axons across the midline (Andrews et al, 2008; Dickson and Zou, 2010; Evans and Bashaw, 2010; Spitzweck et al, 2010; Organisti et al, 2015)
Netrin deficiencies reveal the presence of an additional activity mediating axon guidance across the midline Drosophila has two Netrin genes, NetA and NetB, which are adjacent on the X chromosome (Fig. 1A)

Summary

Introduction

In the central nervous system (CNS) of vertebrates and invertebrates most neurons extend across the midline to form commissures, while the remainder extend on their own side (Tear, 1999; Kaprielian et al, 2001; Garbe and Bashaw, 2004; Evans and Bashaw, 2010). The role of these additional pathways in directing commissural axons across the midline is only revealed in the absence of Netrin signalling. We show that Mushroom body defect (Mud) has a role in a Netrin-independent signalling pathway directing commissural axons to the midline in Drosophila.

Results

Conclusion