Expression of Sympathetic Nervous System Genes in Lamprey Suggests Their Recruitment for Specification of a New Vertebrate Feature

Abstract

The sea lamprey is a basal, jawless vertebrate that possesses many neural crest derivatives, but lacks jaws and sympathetic ganglia. This raises the possibility that the factors involved in sympathetic neuron differentiation were either a gnathostome innovation or already present in lamprey, but serving different purposes. To distinguish between these possibilities, we isolated lamprey homologues of transcription factors associated with peripheral ganglion formation and examined their deployment in lamprey embryos. We further performed DiI labeling of the neural tube combined with neuronal markers to test if neural crest-derived cells migrate to and differentiate in sites colonized by sympathetic ganglia in jawed vertebrates. Consistent with previous anatomical data in adults, our results in lamprey embryos reveal that neural crest cells fail to migrate ventrally to form sympathetic ganglia, though they do form dorsal root ganglia adjacent to the neural tube. Interestingly, however, paralogs of the battery of transcription factors that mediate sympathetic neuron differentiation (dHand, Ascl1 and Phox2b) are present in the lamprey genome and expressed in various sites in the embryo, but fail to overlap in any ganglionic structures. This raises the intriguing possibility that they may have been recruited during gnathostome evolution to a new function in a neural crest derivative.

Dual origin of enteric neurons in vagal Schwann cell precursors and the sympathetic neural crest

“…A recent study in lamprey (37) showed a contribution of the trunk crest but not of the vagal crest to the ENS. Since agnathans are suggested to have no sympathetic neural crest derivative (38), the absence of vagal contribution to the ENS fits with our data that the formerly called "vagal" crest of gnathostomes is for the most part cervical and sympathetic; but it also entails the surprising notion that the vagus nerve itself does not carry Schwann cell precursors-like enteroblasts to the gut of lampreys, when trunk nerves do.…”

Gaskell revisited: new insights into spinal autonomics necessitate a revised motor neuron nomenclature

“…In ascidians, Phox2 expression is limited at larval stages to neurons in the region proposed to be homologous with the vertebrate brainstem, and in the sessile adult is present in neurons associated with the branchial arches (Dufour, Chettouh, Deyts, De Rosa, Goridis, Joly and Brunet, 2006). In lampreys, Phox2 expression is limited to the brainstem, and although its expression in motor neurons has not yet been demonstrated directly, it likely overlaps with motor neurons associated with cranial nerves III–X (Häming, et al, 2011) (lampreys have neither a hypoglossal nerve (they are jawless and tongue-less) nor an accessory nerve (associated with muscles of anterior appendages, absent in lamprey) (Fritzsch and Northcutt, 1993a). …”

“…It has not yet been demonstrated whether Phox2 gene(s) are expressed in lamprey extraocular muscle motor neurons [(Häming, Simoes-Costa, Uy, Valencia, Sauka-Spengler and Bronner-Fraser, 2011) III, IV, VI] and if those motor neurons are dependent on Phox2 expression, as they are on Phox2a in mice (Pattyn, Morin, Cremer, Goridis and Brunet, 1997). It would also be interesting to determine whether hagfish (another cyclostome that separated from a common ancestor with the lampreys about 350 million years ago, (Simakov, Kawashima, Marlétaz, Jenkins, Koyanagi, Mitros, Hisata, Bredeson, Shoguchi and Gyoja, 2015)), which lack extraocular muscles and their innervating cranial nerves (III, IV and VI), exhibit any transient expression of Phox2 in the developing midbrain/hindbrain region where the III and IV nuclei normally develop.…”

“…Neural crest precursors have been claimed to exist in lancelets and ascidians based on molecular and neuroanatomical evidence (Abitua, et al, 2015, Abitua, et al, 2012, Fritzsch and Northcutt, 1993a, Häming, Simoes-Costa, Uy, Valencia, Sauka-Spengler and Bronner-Fraser, 2011), but in these taxa they do not form peripheral ganglia per se but rather other neural crest-typical derivatives such as (scattered) peripheral sensory neurons and mesenchymal cell types (Pasini et al 2012, Häming et al 2011). The evidence for the presence of bona fide autonomic ganglia in cyclostomes is scanty and then only in association with the vagus nerve.…”

Insights into neural crest development and evolution from genomic analysis

“…Lampreys are basal vertebrates that lack several neural crest derivatives, including a neural crest-derived jaw and sympathetic ganglia (Nicol 1952;Häming et al 2011). Nevertheless they possess a SoxE expressing population of migrating neural crest cells (McCauley and Bronner-Fraser 2006) that contribute to branchial arch cartilage, as well as the formation of pigment cells, cranial, and dorsal root ganglia.…”