Academic journal article Genetics

Glial and Neuronal Functions of the Drosophila Homolog of the Human SWI/SNF Gene ATR-X (DATR-X) and the Jing Zinc-Finger Gene Specify the Lateral Positioning of Longitudinal Glia and Axons

Academic journal article Genetics

Glial and Neuronal Functions of the Drosophila Homolog of the Human SWI/SNF Gene ATR-X (DATR-X) and the Jing Zinc-Finger Gene Specify the Lateral Positioning of Longitudinal Glia and Axons

Article excerpt

ABSTRACT

Neuronal-glial communication is essential for constructing the orthogonal axon scaffold in the developing Drosophila central nervous system (CNS). Longitudinal glia (LG) guide extending commissural and longitudinal axons while pioneer and commissural neurons maintain glial survival and positioning. However, the transcriptional regulatory mechanisms controlling these processes are not known. Previous studies showed that the midline function of the jing C^sub 2^H^sub 2^-type zinc-finger transcription factor was only partially required for axon scaffold formation in the Drosophila CNS. We therefore screened for gain-of-function enhancers of jing gain of function in the eye and identified the Drosophila homolog of the disease gene of human α-thalassemia/mental retardation X-linked (ATR-X) as well as other genes with potential roles in gene expression, translation, synaptic transmission, and cell cycle. jing and DATR-X reporter genes are expressed in both CNS neurons and glia, including the LG. Coexpression of jing and DATR-X in embryonic neurons synergistically affects longitudinal connective formation. During embryogenesis, jing and DATR-X have autonomous and nonautonomous roles in the lateral positioning of LG, neurons, and longitudinal axons as shown by cell-specific knockdown of gene expression. jing and DATR-X are also required autonomously for glial survival. jing and DATR-X mutations show synergistic effects during longitudinal axon formation suggesting that they are functionally related. These observations support a model in which downstream gene expression controlled by a potential DATR-X-Jing complex facilitates cellular positioning and axon guidance, ultimately allowing for proper connectivity in the developing Drosophila CNS.

DURING central nervous system (CNS) development, axons navigate long distances and are faced with both attractive and repulsive guidance cues that must be properly interpreted (TESSIER-LAVIGNE and GOODMAN 1996). Many interneurons, whose cell bodies lie next to the CNS midline, must project their axons across the midline to form the commissural tracts. The "decision" of an axon to cross the midline of the Drosophila ventral nerve cord (VNC) and the vertebrate spinal cord depends on the differential response of axons to the midline repellent Slit and to the attractant Netrins (SEEGER et al. 1993; TESSIER-LAVIGNE 1994; BATTYE et al. 1999; KIDD et al. 1999; LONG et al. 2004; BHAT 2005). After commissural axons cross the midline, they turn to fasciculate with the longitudinal tracts that run parallel to the midline and are repelled from the midline by Slit.

The ligand of Slit is Roundabout (Robo), which is located on the longitudinal glia (LG) and associated pioneer neuron growth cones adjacent to the midline (KIDD et al. 1998a; KINRADE et al. 2001). Signaling and cell-cell contact maintain the ipsilateral positions of both LG and connectives. In fact, Slit-Robo signaling cancels out the attraction of longitudinal axons to the CNS midline by Netrin-Frazzled (BHAT 2005). Commissureless (Comm) is a transmembrane protein that prevents the delivery of Robo to the growth cones, specifically in commissural neurons, allowing their axons to cross the midline (TEAR et al. 1996; KELEMAN et al. 2002; KELEMAN et al. 2005). A downregulation of Robo by genetic means or by overexpression of comm results in an excess of axons at the CNS midline (KIDD et al. 1998b). Therefore, the differential localization of Comm, Robo, and Slit determines what directions navigating axons of the scaffold will follow. The Slit-Robo system is an important and conserved mechanism to establish cellular positioning and boundaries in the developing vertebrate and invertebrate nervous systems (KIDD et al. 1999; RAJAGOPALAN et al. 2000a,b; SIMPSON et al. 2000a,b; RASBAND et al. 2003; BARRESI et al. 2005).

The relationship between neurons and glia and the formation of the Drosophila CNS axon tracts has been extensively studied by genetic and cell ablation methods (HIDALGO and BRAND 1997, 2000; BOOTH et al. …

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