Thyroid and endostyle development in cyclostomes provides new insights into the evolutionary history of vertebrates

Abstract

Background The endostyle is an epithelial exocrine gland found in non-vertebrate chordates (amphioxi and tunicates) and the larvae of modern lampreys. It is generally considered to be an evolutionary precursor of the thyroid gland of vertebrates. Transformation of the endostyle into the thyroid gland during the metamorphosis of lampreys is thus deemed to be a recapitulation of a past event in vertebrate evolution. In 1906, Stockard reported that the thyroid gland in hagfish, the sister cyclostome group of lampreys, develops through an endostyle-like primordium, strongly supporting the plesiomorphy of the lamprey endostyle. However, the findings in hagfish thyroid development were solely based on this single study, and these have not been confirmed by modern molecular, genetic, and morphological data pertaining to hagfish thyroid development over the last century. Results Here, we showed that the thyroid gland of hagfish undergoes direct development from the ventrorostral pharyngeal endoderm, where the previously described endostyle-like primordium was not found. The developmental pattern of the hagfish thyroid, including histological features and regulatory gene expression profiles, closely resembles that found in modern jawed vertebrates (gnathostomes). Meanwhile, as opposed to gnathostomes but similar to non-vertebrate chordates, lamprey and hagfish share a broad expression domain of Nkx2-1/2-4, a key regulatory gene, in the pharyngeal epithelium during early developmental stages. Conclusions Based on the direct development of the thyroid gland both in hagfish and gnathostomes, and the shared expression profile of thyroid-related transcription factors in the cyclostomes, we challenge the plesiomorphic status of the lamprey endostyle and propose an alternative hypothesis where the lamprey endostyle could be obtained secondarily in crown lampreys.

Gross anatomy of the Pacific hagfish,Eptatretus burgeri, with special reference to the coelomic viscera

“…The thyroid gland of the cyclostomes is not a glandular organ with clusters of follicles, but rather, the thyroid follicles are scattered throughout the pharynx (Kobayashi, 1987). Hagfish thyroid follicles are similar in early development and morphology to those of gnathostomes and represent the ancestral condition among extant vertebrates (Takagi et al, 2022). Electron microscopic analyses have revealed the presence of dense granules in the thyroid follicular epithelial cells of hagfishes, which are thought to contain iodine (Henderson & Gorbman, 1971; Fujita, 1975; Fujita & Shinkawa, 1975; Suzuki, 1985).…”

“…However, recent studies have suggested that some lamprey characteristics that had been regarded as ancestral to the cyclostomes, such as the larval-type oral apparatus (Miyashita et al, 2021) and the transformation of the larval endostyle into the thyroid after metamorphosis (Takagi et al, 2022), are in fact the derived state from the acquisition of the ammocoete larval stage. Lampreys and hagfish split around 470 to 390 million years ago (Kuraku & Kuratani, 2006), and their morphology subsequently diverged.…”

“…The morphology of the hagfishes is regarded to be highly derived, including the degeneration of eyes because of adaptation to the deep sea (Gabbott et al, 2016; Dong & Allison, 2021), and many studies have instead used lampreys as a model for cyclostomes. However, recent studies have suggested that some lamprey characteristics that had been regarded as ancestral to the cyclostomes, such as the larval-type oral apparatus (Miyashita et al, 2021) and the transformation of the larval endostyle into the thyroid after metamorphosis (Takagi et al, 2022), are in fact the derived state from the acquisition of the ammocoete larval stage. Lampreys and hagfish split around 470 to 390 million years ago (Kuraku & Kuratani, 2006), and their morphology subsequently diverged.…”

Gross anatomy of the Pacific hagfish, Eptatretus burgeri, with special reference to the coelomic viscera

“…In lampreys, the thyroid gland takes on the function of an exocrine organ, known as an endostyle during the larval period. This was long considered to be an ancestral condition, but recently it has been suggested to be a secondary condition (Takagi et al, 2022). Although there is some difference in the arrangement of blood vessels, both lamprey and hagfish have the scattered distribution of thyroid follicles along the bifurcated ventral aorta (for lamprey, see Takagi et al, 2022).…”

“…The morphology of the hagfishes is regarded to be highly derived, including the degeneration of eyes because of adaptation to the deep sea (Dong & Allison, 2021; Gabbott et al, 2016), and many studies have instead used lampreys as a model for cyclostomes. However, recent studies have suggested that some lamprey characteristics that had been regarded as ancestral to the cyclostomes, such as the larval‐type oral apparatus (Miyashita et al, 2021) and the transformation of the larval endostyle into the thyroid after metamorphosis (Takagi et al, 2022), are in fact the derived state from the acquisition of the ammocoete larval stage (still, careful discussion is necessary; see Mallatt, 2023). Lampreys and hagfish split around 470–390 million years ago (Kuraku & Kuratani, 2006; also see Miyashita et al, 2019), and their morphology has highly diverged.…”