Highlights d Microvilli exhibit persistent, active motility driven by actin assembly d Microvillar F-actin cores treadmill during motility d Barbed-end binding factors regulate microvillar motility d Motility promotes intermicrovillar collisions, adhesion, and cluster formation

Highlights d EPS8 and IRTKS puncta mark sites of new microvillus growth d EPS8 and IRTKS puncta remain enriched at the distal tips of nearly all microvilli d Existing microvilli also serve as mothers that give rise to daughter protrusions d Microvilli collapse when membrane wrapping and EPS8/ IRTKS tip enrichment are lost

Our goal was to investigate the neuroprotective effects of galantamine in a mouse model of blast-induced indirect traumatic optic neuropathy (bITON). Galantamine is an FDA-approved acetylcholinesterase inhibitor used to treat mild-moderate Alzheimer’s disease. We exposed one eye of an anesthetized mouse to repeat bursts of over-pressurized air to induce traumatic optic neuropathy. Mice were given regular or galantamine-containing water (120 mg/L) ad libitum, beginning immediately after blast and continuing for one month. Electroretinograms and visual evoked potentials were performed just prior to endpoint collection. Histological and biochemical assessments were performed to assess activation of sterile inflammation, axon degeneration, and synaptic changes. Galantamine treatment mitigated visual function deficits induced by our bITON model via preservation of the b-wave of the electroretinogram and the N1 of the visual evoked potential. We also observed a reduction in axon degeneration in the optic nerve as well as decreased rod bipolar cell dendritic retraction. Galantamine also showed anti-inflammatory and antioxidant effects. Galantamine may be a promising treatment for blast-induced indirect traumatic optic neuropathy as well as other optic neuropathies.

Differentiated transporting epithelial cells present an extensive apical array of microvilli, a brush border, where neighboring microvilli are linked together by intermicrovillar adhesion complexes (IMACs) composed of protocadherins CDHR2 and CDHR5. Although loss-of-function studies provide strong evidence that IMAC function is needed to build a mature brush border, how the IMAC contributes to the stabilization and accumulation of nascent microvilli remains unclear. We found that, early in differentiation, the apical surface exhibits a marginal accumulation of microvilli, characterized by higher packing density relative to medial regions of the surface. While medial microvilli are highly dynamic and sample multiple orientations over time, marginal protrusions exhibit constrained motion and maintain a vertical orientation. Unexpectedly, we found that marginal microvilli span the junctional space and contact protrusions on neighboring cells, mediated by complexes of CDHR2/CDHR5. FRAP analysis indicated that these transjunctional IMACs are highly stable relative to adhesion complexes between medial microvilli, which explains the restricted motion of protrusions in the marginal zone. Finally, long-term live imaging revealed that the accumulation of microvilli at cell margins consistently leads to accumulation in medial regions of the cell. Collectively, our findings suggest that nascent microvilli are stabilized by a capture mechanism that is localized to cell margins and enabled by the transjunctional formation of IMACs. These results inform our understanding of how apical specializations are assembled in diverse epithelial systems.