Raw regulates glial population of the eye imaginal disc

Abstract

Summary Glia are critical for proper development, support, and function of the nervous system. The Drosophila eye has proven an excellent model for gaining significant insight into the molecular mechanisms regulating glial development and function. Recent studies have demonstrated that Raw is required in glia of the central and peripheral nervous systems; however, the function of Raw in glia of the developing eye has not been explored. These studies demonstrate that raw knockdown results in a reduction in the number of glia in the third instar eye imaginal disc and reduced glial spreading across the field of differentiating photoreceptor neurons. Expression of a raw enhancer trap reveals that raw is expressed in eye disc glia. Exploration of the mechanism by which raw knockdown results in glial reduction reveals that Raw is required for glial proliferation and migration into the eye disc. In addition, Raw negatively regulates Jun N‐terminal kinase (JNK) signaling in glia of the developing eye and increased JNK signaling results in a reduction in the number of glia populating the eye disc, similar to that observed upon raw knockdown. Thus, Raw functions as a critical regulator of glial population of the eye imaginal disc by regulating glial proliferation and migration and inhibiting JNK signaling.

Degeneration of Injured Axons and Dendrites Requires Restraint of a Protective JNK Signaling Pathway by the Transmembrane Protein Raw

“…Using this assay we discovered a new mutation on the second chromosome that strongly inhibits axon degeneration in vivo, and have mapped this mutation via whole-genome sequencing to the Drosophila gene raw. Raw is previously known to regulate multiple developmental processes including embryonic dorsal closure, gonad development, glial development, and dendrite morphogenesis (Bates et al, 2008;Jemc et al, 2012;Lee et al, 2015;Hans et al, 2018;Luong et al, 2018). Here we find an essential function for Raw in axonal degeneration via restraint of the JNK MAP kinase and the transcription factors Fos and Jun.…”

“…Previous studies suggest that Raw regulates cell-cell interactions in several developmental events, including dorsal closure, gonad morphogenesis, and dendrite patterning (Bates et al, 2008;Jemc et al, 2012;Lee et al, 2015;Hans et al, 2018;Luong et al, 2018). Recent work has implicated functions for Raw in glial development (Hans et al, 2018;Luong et al, 2018). It is therefore tempting to hypothesize that Raw participates in glia-neuron interactions, which can influence the onset of axonal degeneration as well as the clearance of axonal debris (Beirowski, 2013;Corty and Freeman, 2013).…”

“…The raw dcp-1 allele contains a missense mutation, A532D, which lies in Raw's extracellular domain. Previously characterized mutations in raw are embryonic lethal and cause defects in embryonic dorsal closure, gonad morphogenesis, glial development, and dendrite branching (Bates et al, 2008;Jemc et al, 2012;Lee et al, 2015;Hans et al, 2018;Luong et al, 2018); however, raw dcp-1 mutants are viable and fertile. Because the degeneration phenotype is recessive, we suspected that the raw dcp-1 mutations confer a partial loss in raw function.…”

CG11426 gene product negatively regulates glial population size in the Drosophila eye imaginal disc

“…The numbers are significantly increased in CG11426 loss‐of‐function mutants, while decreased by ectopic expression of CG11426 . Regulation of glial population is thought to be controlled primarily through cell proliferation (Franzdóttir et al., 2009; Hans et al., 2018; Read et al., 2009; Reddy & Irvine, 2011; Witte et al., 2009). However, our results suggested that regulation of glial cell number by CG11426 was primarily due to cell death rather than cell proliferation.…”

“…Due to its morphological and functional similarities to mammalian glia, Drosophila’ s glia is a relevant model system for studying glial functions in mammals including humans (Freeman & Doherty, 2006; Stork et al., 2012). The developing Drosophila eye has been used to study glial cell development, as this system is relatively simple and easy to manipulate (Choi & Benzer, 1994; Franzdóttir et al., 2009; Hans et al., 2018; Rangarajan et al., 1999; Reddy & Irvine, 2011, 2013; Silies et al., 2007). Glial cells in the eye disc, termed retinal basal glia (RBG), originate from the optic stalk and migrate into the eye disc during photoreceptor (PR) differentiation (Figure 1a; Choi & Benzer, 1994; Silies et al., 2007).…”