Hair Cell Development and Regeneration in Zebrafish Lacking the Cannabinoid Receptor2

Hair cells (HCs) are mechanosensory receptors found in sensory epithelia in the vertebrate inner ear that detect sound and head movements. HCs are fragile and prone to damage from various causes like disease, aging, and noise pollution. Unlike mammals, lower vertebrates including birds, amphibians and fish can regenerate HCs. To understand the underlying molecular mechanisms of HCs regeneration, we study the lateral line (LL) in a powerful genetic and regenerative animal model: the zebrafish. The LL is a skin‐deep fish sensory organ that is evolutionarily linked to the vertebrate sensory epithelia of the inner ear. It is composed of stereotypical distributed sensory patches called neuromasts (NMs) which contain HCs that are highly similar in function, cellular structure and gene expression to HCs of the inner ear. LL‐HCs are deflected and activate by surrounding water movements. Using CRISPR‐Cas9 genome editing technology, our laboratory has previously generated a null allele of the cnr2 gene ( cnr2 upr1 ) which is encoding the cannabinoid receptor 2 (CB2). We found that cnr2 mRNA is highly expressed in LL‐HCs. So, we hypothesized that CB2 has a role in the development and the regeneration of LL‐HCs. We counted LL‐HCs at different developmental stages in wild type and homozygote mutant larvae ( cnr2 upr1/upr1 ) to see if their number is affected in the absence of a functional CB2 protein. Next, to trigger vigorous HCs regeneration, we synchronously ablated LL‐HCs by copper treatment of 5‐day post‐fertilization (dpf) wild type and homozygote animals. We counted regenerating LL‐HCs for 3‐day post‐treatment. We will present our preliminary results that will ultimately allow us to conclude on the involvement of CB2 in development and in regeneration of the LL and on a potential link between endocannabinoid signaling and sensory epithelia development and regeneration. Support or Funding Information CREST This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .