The buccohypophyseal canal is an ancestral vertebrate trait maintained by modulation in sonic hedgehog signaling

Abstract

BackgroundThe pituitary gland is formed by the juxtaposition of two tissues: neuroectoderm arising from the basal diencephalon, and oral epithelium, which invaginates towards the central nervous system from the roof of the mouth. The oral invagination that reaches the brain from the mouth is referred to as Rathke’s pouch, with the tip forming the adenohypophysis and the stalk disappearing after the earliest stages of development. In tetrapods, formation of the cranial base establishes a definitive barrier between the pituitary and oral cavity; however, numerous extinct and extant vertebrate species retain an open buccohypophyseal canal in adulthood, a vestige of the stalk of Rathke’s pouch. Little is currently known about the formation and function of this structure. Here we have investigated molecular mechanisms driving the formation of the buccohypophyseal canal and their evolutionary significance.ResultsWe show that Rathke’s pouch is located at a boundary region delineated by endoderm, neural crest-derived oral mesenchyme and the anterior limit of the notochord, using CD1, R26R-Sox17-Cre and R26R-Wnt1-Cre mouse lines. As revealed by synchrotron X-ray microtomography after iodine staining in mouse embryos, the pouch has a lobulated three-dimensional structure that embraces the descending diencephalon during pituitary formation. Polarisfl/fl; Wnt1-Cre, Ofd1-/- and Kif3a-/- primary cilia mouse mutants have abnormal sonic hedgehog (Shh) signaling and all present with malformations of the anterior pituitary gland and midline structures of the anterior cranial base. Changes in the expressions of Shh downstream genes are confirmed in Gas1-/- mice. From an evolutionary perspective, persistence of the buccohypophyseal canal is a basal character for all vertebrates and its maintenance in several groups is related to a specific morphology of the midline that can be related to modulation in Shh signaling.ConclusionThese results provide insight into a poorly understood ancestral vertebrate structure. It appears that the opening of the buccohypophyseal canal depends upon Shh signaling and that modulation in this pathway most probably accounts for its persistence in phylogeny.

Structural and Morphometric Comparison of the Molar Teeth in Pre-eruptive Developmental Stage of PACAP-Deficient and Wild-Type Mice

“…Teeth are typical examples of epithelial appendages, where sequential and reciprocal interactions between oral epithelium and neural crest derived mesenchyme play a pivotal role in their development (Thesleff 2014). Recently, great progress has been made in identifying various key transcription factors and signaling molecules participating in epithelial-mesenchymal crosstalk, involving different pleiotropic morphogens, such as bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), hedgehog (HH) and Wnt proteins (Jernvall and Thesleff 2012;Khonsari et al 2013;Luukko and Kettunen 2014). Among these candidates, HHs have been extensively studied for odontogenic initiation and morphogenesis.…”

Perspective on Stem Cells in Developmental Biology, with Special Reference to Neuroendocrine Systems

“…RP is an epithelial invagination that forms in continuity with the oral ectoderm and extends dorsally toward the ventral diencephalon. RP is also in contact with the anterior border of foregut endoderm (Khonsari et al 2013), and both dorsally and ventrally secreted signals are crucial for proper RP morphogenesis. SHH, independently of its role for formation of the infundibulum, is required for RP development, but it is not expressed in the pouch (Wang et al 2010).…”

Stem Cells in Neuroendocrinology

“…RP is an epithelial invagination that forms in continuity with the oral ectoderm and extends dorsally toward the ventral diencephalon. RP is also in contact with the anterior border of foregut endoderm (Khonsari et al 2013), and both dorsally and ventrally secreted signals are crucial for proper RP morphogenesis. SHH, independently of its role for formation of the infundibulum, is required for RP development, but it is not expressed in the pouch ).…”