Morphogenesis of neurons and glia within an epithelium

Abstract

To sense the outside world, some neurons protrude across epithelia, the cellular barriers that line every surface of our bodies. To study the morphogenesis of such neurons, we examined the C. elegans amphid, in which dendrites protrude through a glial channel at the nose. During development, amphid dendrites extend by attaching to the nose via DYF-7, a type of protein typically found in epithelial apical ECM. Here, we show that amphid neurons and glia exhibit epithelial properties, including tight junctions and apical-basal polarity, and develop in a manner resembling other epithelia. We find that DYF-7 is a fibril-forming apical ECM component that prevents rupture of the tube-shaped glial channel, reminiscent of roles for apical ECM in other narrow epithelial tubes. We also identify a role for FRM-2, a homolog of EPBL15/moe/Yurt which promote epithelial integrity in other systems. Finally, we show that other environmentally-exposed neurons share a requirement for DYF-7. Together, our results suggest that these neurons and glia can be viewed as part of an epithelium continuous with the skin, and are shaped by mechanisms shared with other epithelia.

Epithelial Shaping by Diverse Apical Extracellular Matrices Requires the Nidogen Domain Protein DEX-1 in Caenorhabditis elegans

“…In 1.5-fold embryos and L1 larvae, a discrete spot of DYF-7::SfGFP was observed near the excretory canal cell, but it did not extend through the duct and pore lumens (Figure 1, G and H). The vast majority of DYF-7::SfGFP accumulated near the nose tip, as previously described (Heiman and Shaham 2009;Low et al 2018), and we did not detect any signal in the remainder of the epidermis (Figure 1…”

“…Different ZP components likely confer different physical properties to aECMs, which are specialized for the types of stresses each tissue experiences. For example, embryonic elongation puts the pharyngeal-epidermal connection, the glial-epidermal connection, and the epidermis under tension that ZP proteins (FBN-1, DYF-7, and NOAH-1 and -2, respectively) resist (Heiman and Shaham 2009;Kelley et al 2015;Vuong-Brender et al 2017;Low et al 2018). The duct/pore lumen is likely under stress from fluid flow as well as from morphogenetic forces associated with duct lumen elongation, which may exert both circumferential and longitudinal pressures that must be countered by LET-653 to maintain uniform lumen diameter (Gill et al 2016).…”

“…Mutants used included: dex-1(ns42) I (Heiman and Shaham 2009), dex-1(cs201) I (this study), fbn-1(ns283) III (Kelley et al 2015), dyf-7(ns117) X and dyf-7(ns119) X (Heiman and Shaham 2009). Transgenes used included: aaaEx78 (mini-FBN-1:: mCherry) (Kelley et al 2015), cbcEx1 (dex-1pro,long::GFP,unc-122pro::GFP) (Flatt et al, 2019), hmnEx144 (DYF-7::-SfGFP) (Low et al 2018), csEx402 (dex-1pro::DEX-1, unc-119pro::GFP) (this study), csEx503 (dex-1pro::DEX-1(ecto)::SfGFP, lin-48pro::mRFP) (this study), csEx808 (dex-1pro::ssSfGFP::DEX-1, lin-48pro::mRFP) (this study), csIs61 (RDY-2::GFP, lin-48pro::mRFP) I (Gill et al 2016), csIs66 (let-653pro::ssSfGFP::LET-653(ZP), let-653pro:PH-mCherry, lin-48p::mRFP) X, jcIs1 (AJM-1::GFP, rol-6d) IV (Köppen et al 2001), nsEx1339 (pMH118 = pJIM20dex-1pro:his-24-mCherry, -pRF4) (Heiman and Shaham 2009), nsEx1404(pMH136 = pJIM20dex-1prolong:his-24-mCherry, pRF4) (Heiman and Shaham 2009), qnEx59 (dct-5pro:: mCherry, unc-119+) (Abdus-Saboor et al 2011), and zwEx113 (inx-13pro::GFP, lin-15+) (Altun et al 2009). CRISPR insertions used included: noah-1[mc68 (noah-1:: mCherry)] I and noah-2[mc93 (noah-2::gfp)] IV (Vuong-Brender et al 2017).…”

“…We sought new mutants with ZP-like phenotypes and identified a new allele of the previously described gene dex-1. DEX-1 is a proposed partner of the ZP protein DYF-7 in a dendritic cap matrix that anchors sensory dendrites and glia to the nose tip (Heiman and Shaham 2009;Low et al 2018). In both dex-1 and dyf-7 mutants, dendrites retract into the body cavity under tension from elongation forces in the embryo.…”

Direct glia-to-neuron transdifferentiation gives rise to a pair of male-specific neurons that ensure nimble male mating

“…Each sensillum is composed of the dendrites of one or more sensory neurons enveloped by a channel, usually composed of a single sheath glial cell and a single socket-glial cell. These sensilla can be viewed as part of an epithelium, continuous with the skin, and are shaped by mechanisms shared with other epithelia ( Low et al, 2019 ). Socket-glial cells are highly polarised and adhere to the hypodermis at the distal end of their process where they form a small, ring-like hollow pore in the cuticle through which the sensory dendrites can access the outside world.…”