Fgf8 regulates first pharyngeal arch segmentation through pouch-cleft interactions

Abstract

Introduction: The pharyngeal arches are transient developmental structures that, in vertebrates, give rise to tissues of the head and neck. A critical process underlying the specification of distinct arch derivatives is segmentation of the arches along the anterior-posterior axis. Formation of ectodermal-endodermal interfaces is a key mediator of this process, and although it is essential, mechanisms regulating the establishment of these interfaces vary between pouches and between taxa.Methods: Here, we focus on the patterning and morphogenesis of epithelia associated with the first pharyngeal arch, the first pharyngeal pouch (pp1) and the first pharyngeal cleft (pc1), and the role of Fgf8 dosage in these processes in the mouse model system.Results: We find that severe reductions of Fgf8 levels disrupt both pp1 and pc1 development. Notably, out-pocketing of pp1 is largely robust to Fgf8 reductions, however, pp1 extension along the proximal-distal axis fails when Fgf8 is low. Our data indicate that Fgf8 is required for specification of regional identity in both pp1 and pc1, for localized changes in cell polarity, and for elongation and extension of both pp1 and pc1.Discussion: Based on Fgf8-mediated changes in tissue relationships between pp1 and pc1, we hypothesize that extension of pp1 requires physical interaction with pc1. Overall, our data indicate a critical role for the lateral surface ectoderm in segmentation of the first pharyngeal arch that has previously been under-appreciated.

Fgf signalling is required for gill slit formation in the skate, Leucoraja erinacea

“…Given established roles for Fgf8 and Fgf3 signalling in the control of pharyngeal pouch development or morphogenesis in zebrafish ( Crump et al, 2004 ), lamprey ( Jandzik et al, 2014 ) and mouse ( Zbasnik and Fish, 2023 ), we examined spatial expression of Fgf8 and Fgf3 by mRNA in situ hybridisation during skate gill slit development. We found that discrete Fgf8 expression domains appear in a rostral-to-caudal sequence, in the vicinity of each developing pharyngeal pouch, from S18–S22 ( Fig.…”

“…But unlike in zebrafish, where pharyngeal pouches fail to form in the absence of Fgf signalling, formation of the first pharyngeal pouch in mouse appears to be laregly robust to reductions in Fgf8 dosage. Instead, Fgf8 signalling is required in mouse for separation of the mandibular and hyoid arches via reshaping and elongation of the first pharyngeal pouch and interaction of this pouch with adjacent ectoderm ( Zbasnik and Fish, 2023 ).…”

Fgf signalling is required for gill slit formation in the skate,Leucoraja erinacea

“…Given established roles for Fgf8 and Fgf3 signalling in the control of pharyngeal pouch development or morphogenesis in zebrafish (Crump et al, 2004), lamprey (Jandzik et al, 2014) and mouse (Zbasnik, 2023), we examined spatial expression of Fgf8 and Fgf3 by mRNA in situ hybridisation during skate gill slit development. We found that discrete Fgf8 expression domains appear in a rostral-to-caudal sequence, in the vicinity of each developing pharyngeal pouch, from S18-S22 (Fig.…”

“…In the lamprey, Fgf3 and Fgf8 are expressed in the posterior region of each pharyngeal endodermal pouch with Fgf8 additionally expressed in overlying pharyngeal ectoderm (Jandzik et al, 2014), and this regionalised expression of Fgf8 and/or Fgf3 within pharyngeal endormal pouches is conserved in chick (Veitch et al, 1999) and skate (reported here). In mouse Fgf8 is expressed broadly throughout pharyngeal pouch endoderm and in overlying ectoderm, as well as in splanchnic mesoderm (Abu-Issa et al, 2002;Zbasnik et al, 2023), while in zebrafish fgf8 is expressed in pharyngeal mesoderm during pouch formation (Choe and Crump, 2014).…”

“…But unlike in zebrafish, where pharyngeal pouches fail to form in the absence of Fgf signalling, formation of the first pharyngeal pouch in mouse appears to be laregly robust to reductions in Fgf8 dosage. Instead, Fgf8 signalling is required in mouse for separation of the mandibular and hyoid arches via reshaping and elongation of the first pharyngeal pouch and interaction of this pouch with adjacent ectoderm (Zbasnik, 2023).…”