Loss of the Extracellular Matrix Protein DIG-1 Causes Glial Fragmentation, Dendrite Breakage, and Dendrite Extension Defects

Abstract

The extracellular matrix (ECM) guides and constrains the shape of the nervous system. In C. elegans, DIG-1 is a giant ECM component that is required for fasciculation of sensory dendrites during development and for maintenance of axon positions throughout life. We identified four novel alleles of dig-1 in three independent screens for mutants affecting disparate aspects of neuronal and glial morphogenesis. First, we find that disruption of DIG-1 causes fragmentation of the amphid sheath glial cell in larvae and young adults. Second, it causes severing of the BAG sensory dendrite from its terminus at the nose tip, apparently due to breakage of the dendrite as animals reach adulthood. Third, it causes embryonic defects in dendrite fasciculation in inner labial (IL2) sensory neurons, as previously reported, as well as rare defects in IL2 dendrite extension that are enhanced by loss of the apical ECM component DYF-7, suggesting that apical and basolateral ECM contribute separately to dendrite extension. Our results highlight novel roles for DIG-1 in maintaining the cellular integrity of neurons and glia, possibly by creating a barrier between structures in the nervous system.

Dendrite morphogenesis in Caenorhabditis elegans

“…Specifically, the gigantic ECM protein DIG-1 and the cell adhesion molecules SAX-7 /L1CAM, PTP-3 /LAR, and the Fat-like cadherin CDH-4 are required to maintain dendrite fasciculation in the amphid and other ciliated dendrite bundles ( Burket et al . 2006 ; Yip and Heiman 2018 ; Chong et al . 2021 ).…”

“…Moreover, dendrite breakage is observed in many ciliated dendrites in the head upon loss of the cytoskeletal protein UNC-70 /β-Spectrin ( Hammarlund et al . 2007 ) and specifically in the BAG dendrite upon loss of DIG-1 ( Chong et al . 2021 ).…”