Midline axon guidance in the Drosophila embryonic central nervous system

Abstract

Studies in the fruit fly Drosophila melanogaster have provided many fundamental insights into the genetic regulation of neural development, including the identification and characterization of evolutionarily conserved axon guidance pathways and their roles in important guidance decisions. Due to its highly organized and fast-developing embryonic nervous system, relatively small number of neurons, and molecular and genetic tools for identifying, labeling, and manipulating individual neurons or small neuronal subsets, studies of axon guidance in the Drosophila embryonic CNS have allowed researchers to dissect these genetic mechanisms with a high degree of precision. In this review, we discuss the major axon guidance pathways that regulate midline crossing of axons and the formation and guidance of longitudinal axon tracts, two processes that contribute to the development of the precise three-dimensional structure of the insect nerve cord. We focus particularly on recent insights into the roles and regulation of canonical midline axon guidance pathways, and on additional factors and pathways that have recently been shown to contribute to axon guidance decisions at and near the midline.

Drosophila glia: Few cell types and many conserved functions

“…The midline glial cells acquire their fate due to the function of the transcription factor Single‐minded and the activity of the EGF‐receptor signaling pathway (Klämbt, ; Klämbt et al, ). They are derived from the mesectoderm and are found at the symmetry axis of the nervous system, where they participate in patterning of the nervous system by inducing cell fate and organization of axonal projections (Howard, Brown, Wadsworth, & Evans, ; Menne, Luer, Technau, & Klämbt, ). The midline glial cells show a stereotypic migration pattern and engulf the commissural axon tracts (Klämbt et al, ; Stork et al, ; Wheeler et al, ; Wheeler, Kearney, Guardiola, & Crews, ).…”

“…However, no clearcut roles of glial cells on early axonal patterning could be provided and even the gcm mutant has a suprisingly normal appearing axon pattern (Takizawa & Hotta, ). The only exception can be seen for the midline glia which instruct the growth of commissural axons across the CNS midline by expressing the two guidance cues, Netrin and Slit (Howard et al, ). Drosophila glial cells, however, participate in the adjustment of optic centers where they relay a signal from photoreceptors to induce lamina neuronal differentiation (Fernandes et al, ).…”

“…The midline glial cells acquire their fate due to the function of the transcription factor Single-minded and the activity of the EGF-receptor signaling pathway (Klämbt, 1993;. They are derived from the mesectoderm and are found at the symmetry axis of the nervous system, where they participate in patterning of the nervous system by inducing cell fate and organization of axonal projections (Howard, Brown, Wadsworth, & Evans, 2017;Menne, Luer, Technau, & Klämbt, 1997).…”

“…The only exception can be seen for the midline glia which instruct the growth of commissural axons across the CNS midline by expressing the two guidance cues, Netrin and Slit (Howard et al, 2017). Drosophila glial cells, however, participate in the adjustment of optic centers where they relay a signal from photoreceptors to induce lamina neuronal differentiation .…”

Trans-Axonal Signaling in Neural Circuit Wiring

“…A panoply of factors are known to provide long-range and/or contact-mediated signals, including the classical guidance cues Ephrins, Slits, Netrins, and Semaphorins [ 13 ], adhesion molecules [ 14 , 15 ], neurotrophic and growth factors [ 16 ], or morphogens such as Sonic Hedgehog (Shh), Bone morphogenetic proteins (BMPs), and Wnts [ 17 , 18 ]. The activity of these signaling factors has mostly been studied in classical model systems for axon guidance such as the sensory and motor innervation of the limb [ 19 ], the midline [ 20 , 21 ], and the retinotectal and olfactory systems [ 22 , 23 , 24 , 25 ]. These models have been instrumental in defining the general rules of axon navigation and targeting.…”