Insights into Electroreceptor Development and Evolution from Molecular Comparisons with Hair Cells

Abstract

The vertebrate lateral line system comprises a mechanosensory division, with neuromasts containing hair cells that detect local water movement ("distant touch"); and an electrosensory division, with electrosensory organs that detect the weak, low-frequency electric fields surrounding other animals in water (primarily used for hunting). The entire lateral line system was lost in the amniote lineage with the transition to fully terrestrial life; the electrosensory division was lost independently in several lineages, including the ancestors of frogs and of teleost fishes. (Electroreception with different characteristics subsequently evolved independently within two teleost lineages.) Recent gene expression studies in a non-teleost actinopterygian fish suggest that electroreceptor ribbon synapses employ the same transmission mechanisms as hair cell ribbon synapses, and show that developing electrosensory organs express transcription factors essential for hair cell development, including Atoh1 and Pou4f3. Previous hypotheses for electroreceptor evolution suggest either that electroreceptors and hair cells evolved independently in the vertebrate ancestor from a common ciliated secondary cell, or that electroreceptors evolved from hair cells. The close developmental and putative physiological similarities implied by the gene expression data support the latter hypothesis, i.e., that electroreceptors evolved in the vertebrate ancestor as a "sister cell-type" to lateral line hair cells.

Fig. 1

Phylogeny showing the distribution of lateral line sensory divisions among living vertebrates, with the invertebrate chordates shown for reference. Black font indicates possession of both the mechanosensory division and the electrosensory division (the latter responding to low-frequency, cathodal stimuli, with the dorsal octavolateral nucleus as the hindbrain target of lateral line afferents projecting via the dorsal root of the anterior lateral line nerve). Gray font indicates possession of the mechanosensory division only, except for the amniotes (), which lost the whole lateral line system during the transition to fully terrestrial life, and actinopterygian teleost fishes (≠), in which a few groups independently evolved lateral line electroreception responding to anodal stimuli, with an electrosensory lateral line lobe as the hindbrain target of lateral line afferents projecting via both anterior and posterior lateral line nerves.

Fig. 2

Genes important for transmission at the hair cell ribbon synapse are expressed in electrosensory organs in the paddlefish. (A) Schematic showing the distribution of neuromasts in canals, flanked by large fields of electrosensory ampullary organs, on the head of a late-larval paddlefish (at the onset of independent feeding). The caudal box outlines the region shown at higher power in panels C, D; the rostral box outlines the region shown at higher power in panels E–G. (B–G) In situ hybridization (shown in skin-mounts in panels C–G: white dotted lines indicating the approximate position of lateral line canals, within which neuromasts are buried) reveals expression of hair cell ribbon synapse-associated genes in ampullary organs, as well as neuromasts, for (B) Cacna1d, encoding the pore-forming subunit of Ca_v1.3; (C) Cacnb2, encoding the Ca_vβ2 auxiliary subunit for Ca_v1.3 in hair cells (expression is very weak in neuromasts: compare with panel D for neuromast distribution); (D) Scl17a8, encoding Vglut3 (asterisk indicates damage to the skin-mount); (E) Otof, encoding otoferlin; (F) Rims2, encoding Rab3-interacting molecules 2α and β, which recruit Ca_v1.3 channels to the membrane under the presynaptic ribbon in hair cells; (G) the N-terminal A-domain sequence of Ctbp2, encoding Ribeye. Scale-bars: 200 μm in B; 100 μm in C (panels D–G are shown at the same magnification as panel C). Abbreviations: ao, ampullary organs; e, eye; io, infraorbital neuromast line; nm, neuromasts; ol, otic neuromast line; so, supraorbital neuromast line. (A color version of this figure is available online.)

Fig. 3

Transcription factor genes important for hair cell development are expressed in developing electrosensory organs in the paddlefish. (A–E) In situ hybridization in paddlefish embryos reveals expression in both developing neuromasts and ampullary organs of (A) Six1 and (B) Eya1 (expression of both is also seen in the posterior lateral line primordium migrating along the trunk); (C) Sox2, (D) Atoh1 (the inset shows neuromast lines at an earlier stage of development) and (E) Pou4f3 (Brn3c). (F–H²) The bHLH transcription factor gene Neurod4 is expressed in ampullary organs but not neuromasts. The dotted white lines in panel G show the approximate position of the neuromast lines. H–H² show a transverse section through the head (near the eye). Panel H shows Neurod4 expression in an ampullary organ. Panel H¹ shows immunostaining for a calcium-buffering protein (an oncomodulin-related beta-parvalbumin; see Modrell et al. 2017) expressed in both neuromast hair cells and electroreceptors, which shows a Neurod4-negative neuromast dorsal to a Neurod4-positive ampullary organ. Panel H² shows DAPI, which stains all nuclei. Scale bars: 500 μm in A (panels B–E shown at the same magnification as panel A); 500 μm in F; 100 μm in G; and 50 μm in H. Abbreviations: ao, ampullary organ; e, eye; nm, neuromasts; pll, posterior lateral line primordium. (A color version of this figure is available online.).