Patterning of the apical extracellular matrix at sense organs

Abstract

Communication between sense organs and the outside world is tightly regulated and requires a key interface that lies at the center: the apical extracellular matrix (aECM). The aECM is a complex network of secreted macromolecules whose structure and composition are tailored to the function of a particular sense organ. As all animals need to sense a wide range of environmental cues, including light, odors, tastes, and physical forces, a diverse array of specialized aECM have evolved to mediate the capture and transmission of these cues to sensory cells. To elucidate the cellular and molecular mechanisms that pattern aECM, we studied specializations of the cuticle aECM that overlies sense organs in the nematode C. elegans. We specifically investigated how two distinct types of cuticle – a closed sheet versus an open pore – are built to support either mechanosensory or chemosensory function, respectively. First, in Chapter 2, we focused on how the cuticle aECM overlying the cephalic sense organ in the head is remodeled from a closed sheet to a ~200 nm pore in adult males to accommodate a male-specific chemosensory neuron used in pheromone detection. We discovered that a male-specific switch in gene expression in a single glial cell (the CEP socket) is necessary and sufficient to induce formation of the cuticle pore. We determined that this switch is controlled by opposing regulators and includes expression of a Hedgehog-related aECM protein that localizes transiently to nanoscale rings at sites of pore formation. We demonstrate that an individual cell can pattern the aECM by switching between discrete gene expression modules. Next, in Chapter 3, we developed new genetic tools to further investigate the role of glia in patterning the cuticle aECM at sense organs. We identified new cell-type-specific markers for distinct glial subtypes and found that glia express different collagen genes, depending on whether the sense organ contains an open pore or a closed sheet of cuticle. In Chapter 4, we demonstrate the presence of highly sense organ-specific aECM by determining that two collagens – COL-53 and COL-56 – are specifically co-expressed in the CEP socket glial cell of adult males. Whereas COL-53 forms a tube-like structure that lines the pore that a male chemosensory neuron protrudes through, COL-56 forms a flat sheet that sits above the cilium of a mechanosensory neuron. These findings suggest that aECM contains discrete local features built from a distinct set of aECM components. Altogether, this work shows that aECM, unlike what is generally assumed, is not a uniform, static meshwork. Instead, aECM is highly structured, precisely patterned, and contains local features that reflect the gene expression modules expressed in the underlying cells.