PROS-1/Prospero Is a Major Regulator of the Glia-Specific Secretome Controlling Sensory-Neuron Shape and Function in C. elegans

Abstract

SUMMARY Sensory neurons are an animal’s gateway to the world, and their receptive endings, the sites of sensory signal transduction, are often associated with glia. While glia are known to promote sensory-neuron functions, the molecular bases of these interactions are poorly explored. Here we describe a post-developmental glial role for the PROS-1/Prospero/PROX1 homeodomain protein in sensory-neuron function in C. elegans. Using glia expression profiling, we demonstrate that, unlike previously characterized cell fate roles, PROS-1 functions post-embryonically to control sense-organ glia-specific secretome expression. PROS-1 functions cell autonomously to regulate glial secretion and membrane structure, and non-cell autonomously to control the shape and function of the receptive endings of sensory neurons. Known glial genes controlling sensory-neuron function are PROS-1 targets, and we identify additional PROS-1-dependent genes required for neuron attributes. Drosophila Prospero and vertebrate PROX1 are expressed in post-mitotic sense-organ glia and in astrocytes, suggesting conserved roles for this class of transcription factors.

Coordinated morphogenesis of neurons and glia

“…non-dauer) growth conditions, laser ablation of single glial cells and cell-specific inhibition of secretion in glia revealed that glia are also required to maintain the shape of neuronal REs embedded within them[40,41]. For example, RNAi-mediated knockdown of glial-enriched genes demonstrated that the transcription factor PROS-1/Prospero functions in glia to regulate the shape of associated dendritic REs[42]. …”

IGDB-2, an Ig/FNIII protein, binds the ion channel LGC-34 and controls sensory compartment morphogenesis in C. elegans

“…We favor the latter model based on the following observations. First, both igdb-2 and daf-6 are expressed in AMso and AMsh glia (Wallace et al, 2016; S.W. Wallace, unpublished results; and Perens and Shaham, 2005).…”

“…All fluorescence images were analyzed with ImageJ (NIH). For transmission electron microscopy, animals were sectioned and imaged as previously described (Perens and Shaham, 2005; Wallace et al, 2016). …”

“…IGDB-2 co-immunoprecipitates with LGC-34, purified with anti-GFP beads (top), and vice versa, with anti-FLAG beads (bottom). (D) Gene expression profiling of daf-6 , igdb-2 , and lgc-34 in amphid sheath glia and other cells of the worm (Based on Wallace et al, 2016; and S.W. Wallace, unpublished results).…”

“…Glial loss or manipulation in this animal leads to profound sensory and synaptic deficits (Bacaj et al, 2008; Colón-Ramos et al, 2007; Felton and Johnson, 2011; Singhvi et al, 2016; Wallace et al, 2016). Importantly, interactions between single glia and neurons can be interrogated at the level of neuronal activity and animal behavior (Oikonomou and Shaham, 2011).…”