Background: Vertebrate epithelial appendages constitute a diverse group of organs that includes integumentary
structures such as reptilian scales, avian feathers and mammalian hair. Recent studies have provided new evidence for
the homology of integumentary organ development throughout amniotes, despite their disparate fnal morphologies.
These structures develop from conserved molecular signalling centres, known as epithelial placodes. It is not yet
certain whether this homology extends beyond the integumentary organs of amniotes, as there is a lack of knowledge
regarding their development in basal vertebrates. As the ancient sister lineage of bony vertebrates, extant chondrichthyans
are well suited to testing the phylogenetic depth of this homology. Elasmobranchs (sharks, skates and
rays) possess hard, mineralised epithelial appendages called odontodes, which include teeth and dermal denticles
(placoid scales). Odontodes constitute some of the oldest known vertebrate integumentary appendages, predating
the origin of gnathostomes. Here, we used an emerging model shark (Scyliorhinus canicula) to test the hypothesis that
denticles are homologous to other placode-derived amniote integumentary organs. To examine the conservation
of putative gene regulatory network (GRN) member function, we undertook small molecule inhibition of fbroblast
growth factor (FGF) signalling during caudal denticle formation.
Results: We show that during early caudal denticle morphogenesis, the shark expresses homologues of conserved
developmental gene families, known to comprise a core GRN for early placode morphogenesis in amniotes. This
includes conserved expression of FGFs, sonic hedgehog (shh) and bone morphogenetic protein 4 (bmp4). Additionally,
we reveal that denticle placodes possess columnar epithelial cells with a reduced rate of proliferation, a conserved
characteristic of amniote skin appendage development. Small molecule inhibition of FGF signalling revealed
placode development is FGF dependent, and inhibiting FGF activity resulted in downregulation of shh and bmp4
expression, consistent with the expectation from comparison to the amniote integumentary appendage GRN.
Conclusion: Overall, these fndings suggest the core GRN for building vertebrate integumentary epithelial appendages
has been highly conserved over 450 million years. This provides evidence for the continuous, historical homology
of epithelial appendage placodes throughout jawed vertebrates, from sharks to mammals. Epithelial placodes
constitute the shared foundation upon which diverse vertebrate integumentary organs have evolved