Epithelia delimits glial apical polarity against mechanical shear to maintain glia-neuron architecture

For an organ to maintain proper architecture and function, its different component cell-types must coordinate their cell-shapes with each other through life. While cell-intrinsic developmental mechanisms driving homotypic cell-cell coordination are known, how heterotypic cells collectively regulate cell-shape is less-clear. We report that, in a sense-organ, epithelial cells delimit and maintain polarity domains of contacting glia, and thereby, associated neuron shapes throughout life. Briefly, Hsp co-chaperone UNC-23/BAG2 keeps epithelial apical domains from deforming with animal movement. Epithelial apical domains stretch aberrantly and progressively in adult unc-23 mutant animals, which in an FGFR-dependent manner, dislocates glial apical cytoskeleton proteins SMA-1/{beta}H-Spectrin and actin. This alters glial apical polarity and cell shape, and concomitantly, associated neuron-ending shape. Notably, UNC-23 acts temporally at a developmental critical period to maintain glia-neuron shape in adults, and spatially within a defined anatomical zone. Lastly, intervention in either epithelia, glia or neuron ameliorate or phenocopy unc-23 neural defects. Epi/endothelia resist mechanical stress and contact glia-neuron units across central/peripheral nervous systems and species, and all components of the identified molecular pathway are conserved and disease-relevant. Thus, we posit that analogous epithelia-glia mechanobiological coupling may broadly regulate glia-neuron shapes through animal life.