# Nerve Growth Factor Receptor (NGFR/p75NTR) of the Small‐Spotted Catshark (Scyliorhinus canicula): Evolutionary Conservation and Brain Function

## TL;DR

This study explores the p75NTR receptor in a shark species, revealing its brain expression and functional conservation across vertebrates, including mammals.

## Contribution

The first description of p75NTR brain expression in a basal vertebrate and demonstration of its functional conservation across species.

## Key findings

- p75NTR is expressed in the brain of the small-spotted catshark (Scyliorhinus canicula).
- The shark p75NTR complements a mammalian PC-12 cell line lacking p75NTR, showing functional conservation.
- The study reveals evolutionary parallels between ancient vertebrates and mammals in p75NTR function.

## Abstract

The p75NTR receptor, a member of the tumor necrosis factor (TNF) receptor superfamily, can participate in signaling pathways either by forming heteromeric complexes with other receptors, such as the Trk family (tropomyosin receptor kinases), or by functioning independently. p75NTR was investigated prevalently in the brain and retina of mammals, whereas almost nothing is known about its conservation among species. Here, we reconstructed the phylogenetic arb of p75NTR and described for the first time the p75NTR expression in the brain of the basal vertebrate Chondrichthyan Scyliorhinus canicula (S. canicula), uncovering the existing parallelism between ancient vertebrates and mammals. p75NTR functional conservation among vertebrates was further investigated by cloning the S. canicula nerve growth factor (NGF) and performing the canonical posterior commissure (PC)‐12 differentiation assay, which results in standard neurite‐like production. We then investigated the S. canicula p75NTR, which proves to be capable of complementing a specific clone of PC‐12 lacking p75NTR (PC‐12 p75NTR−/−). All together, our results highlighted the expression and functional conservation of p75NTR among vertebrates during the evolution.

p75NTR expression in the brain of the basal vertebrate Scyliorhinus canicula revealed its conservation across species. Functional conservation among vertebrates was demonstrated (i) by performing the canonical PC‐12 differentiation assay with the S. canicula NGF and (ii) by complementing the p75NTR absence in a PC‐12 p75NTR−/− knock‐out clone with the S. canicula p75NTR.