Specializations of intercellular junctions are associated with the presence and absence of hair cell regeneration in ears from six vertebrate classes

Abstract

Sensory hair cell losses lead to hearing and balance deficits that are permanent for mammals, but temporary for nonmammals because supporting cells in their ears give rise to replacement hair cells. In mice and humans, vestibular supporting cells grow exceptionally large circumferential F-actin belts and their junctions express E-cadherin in patterns that strongly correlate with postnatal declines in regeneration capacity. In contrast, chicken supporting cells retain thin F-actin belts throughout life and express little E-cadherin. To determine whether the junctions in chicken ears might be representative of other ears that also regenerate hair cells, we investigated inner ears from dogfish sharks, zebrafish, bullfrogs, Xenopus, turtles, and the lizard, Anolis. As in chickens, the supporting cells in adult zebrafish, Xenopus, and turtle ears retained thin circumferential F-actin belts and expressed little E-cadherin. Supporting cells in adult sharks and bullfrogs also retained thin belts, but were not tested for E-cadherin. Supporting cells in adult Anolis exhibited wide, but porous webs of F-actin and strong E-cadherin expression. Anolis supporting cells also showed some cell cycle reentry when cultured. The results reveal that the association between thin F-actin belts and low E-cadherin is shared by supporting cells in anamniotes, turtles, and birds, which all can regenerate hair cells. Divergent junctional specializations in supporting cells appear to have arisen independently in Anolis and mammals. The presence of webs of F-actin at the junctions in Anolis appears compatible with supporting cell proliferation, but the solid reinforcement of the F-actin belts in mammals is associated with its absence.