Coordinate development of skin cells and cutaneous sensory axons in zebrafish

Abstract

Peripheral sensory axons innervate the epidermis early in embryogenesis to detect touch stimuli. To characterize the time course of cutaneous innervation and the nature of interactions between sensory axons and skin cells at early developmental stages, we conducted a detailed analysis of cutaneous innervation in the head, trunk, and tail of zebrafish embryos and larvae from 18 to 78 hours postfertilization. This analysis combined live imaging of fish expressing transgenes that highlight sensory neurons and skin cells, transmission electron microscopy (TEM), and serial scanning electron microscopy (sSEM). In zebrafish, the skin initially consists of two epithelial layers, and all of the axons in the first wave of innervation are free endings. Maturation of the epithelium coincides with, but does not depend on, its innervation by peripheral sensory axons. We found that peripheral axons initially arborize between the two epithelial skin layers, but not within the basal lamina, as occurs in other organisms. Strikingly, as development proceeds, axons become tightly enveloped within basal keratinocytes, an arrangement suggesting that keratinocytes may serve structural or functional roles, akin to Schwann cells, in somatosensation mediated by these sensory neurons.

Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish

“…Interestingly, we observed prominent MMP-13 expression in the dermis of both adult vehicle and paclitaxel-treated animals, yet dermal axons are not affected by MMP-13 activity. One possible explanation is that the dermis contains myelinated axons which do not establish direct contact with the microenvironment, unlike unmyelinated axons in the epidermis (13,14). This is further evidence that interactions between keratinocytes and unmyelinated axons might play a role in paclitaxel neurotoxicity in zebrafish.…”

“…The palms and soles are more frequently injured and exposed to biomechanical stresses, and cutaneous axons, for instance, are receptive to mechanical stress through binding via integrin receptors to the extracellular matrix (ECM) (12). Moreover, sensory axons and keratinocytes are in close apposition (13,14) and have been shown to communicate through various molecular mechanisms. For instance, after injury keratinocytes promote axon regeneration by secreting hydrogen peroxide (H 2 O 2 ) (15).…”

LAR Receptor Tyrosine Phosphatases and HSPGs Guide Peripheral Sensory Axons to the Skin

“…RT-PCR verified that MO1 effectively altered splicing, creating truncated mRNAs coding for nonfunctional proteins (supplemental Figure S2). These morpholinos were injected into embryos carrying two transgenic reporters—sensory:GFP to visualize somatosensory neurons [36, 37] and krt4:dsRed to visualize the two epithelial layers making up the larval zebrafish skin [38]. To standardize our analysis, we collected confocal images of a 416 square micrometer region of the trunk (Figure 2A–C, supplemental Movie S1) after 48 hpf, when sensory neurons have finished arborizing.…”

Enclosure of Dendrites by Epidermal Cells Restricts Branching and Permits Coordinated Development of Spatially Overlapping Sensory Neurons

“…Most da neuron dendrites grow over the ECM near the basal surface of the epidermal cell layer in a largely two dimensional array. As larval development proceeds, segments of dendrites from the highly branched C4da neurons lose integrin-mediated contact with the ECM and become enclosed within invaginations of the epidermal cell membrane (Jiang et al, 2014), similarly to neurites of vertebrate sensory neurons (O’Brien et al, 2012). When integrin-mediated contact of C4da neurons with the ECM is disrupted experimentally, dendrite enclosure is increased and the loss of dendrite-ECM interaction results in aberrant dendrite crossings within and between C4da neuron arbors, possibly by circumventing contact-mediated mechanisms that promote self-avoidance and tiling (Han et al, 2012; Kim et al, 2012).…”