The Fgf8 subfamily (Fgf8, Fgf17 and Fgf18) is required for closure of the embryonic ventral body wall.

Michael Boylan,Mark Lewandoski,David M Ornitz,Matthew J Anderson

doi:10.1242/dev.189506

Abstract

ABSTRACTThe closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are extruded. By refining where and when these genes are required using different Cre lines, we show that Fgf8 and Fgf17 are required in the presomitic mesoderm, whereas Fgf18 is required in the somites. This study identifies complex and multifactorial origins of ventral wall defects and has important implications for understanding their origins during embryonic development.

Highlights

Embryonic ventral wall (VW) defects are a class of congenital abnormality and are relatively frequently encountered in the clinic
The Fgf8 subfamily is expressed in progenitors of the primary and secondary body wall We first examined the expression patterns of Fgf8 (Fig. 1A-E), Fgf17 (Fig. 1F-J) and Fgf18 (Fig. 1K-O) from E7.75 through to E11.5 using RNA whole-mount in situ hybridization reaction (WISH)
The results we have obtained far present something of a conundrum: how does the loss of Fgf8 and Fgf17 in the presomitic mesoderm (PSM) cause omphalocele at E13.5 and later? As fibroblast growth factor (FGF) signaling is known to be essential for both maintaining a pool of progenitor tissue within the PSM (Naiche et al, 2011) and for somitogenesis (Dubrulle et al, 2001), we looked for defects in these two processes in our TCre Fgf8 subfamily conditional mutant mouse line

Summary

Introduction

Embryonic ventral wall (VW) defects are a class of congenital abnormality and are relatively frequently encountered in the clinic. Omphalocele is a VW defect where the viscera are herniated through an enlarged umbilical ring. The organs remain covered by the amnion (Williams, 2008). Omphalocele is sometimes confused with another VW defect, gastroschisis, and this confusion has been noted in the literature (Carnaghan et al, 2013; Williams, 2008). The defect is centered on the umbilical ring and the viscera are contained within the amniotic membrane unless the membrane has ruptured (Brewer and Williams, 2004a). In gastroschisis the defect is dextral to the umbilical ring, usually only loops of midgut are herniated, and

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