Gastric hypoplasia in mice lacking fibroblast growth factor 9.

Abstract

Background: Fibroblast Growth Factor 9 (Fgf9) and its paralog Fgf20 are expressed in the developing stomach. We investigate the role of these growth factors during gastric development, using combinations of null alleles.

Results: Analysis of expression databases showed that Fgf9 is expressed in gastric endoderm and surrounding mesoderm such as the mesothelium as early as E8.5, and Fgf20 is expressed in the gastric progenitors of the glandular stomach. To explore whether Fgf9 and Fgf20 are important for gastric development, we examined embryonic stomachs from Fgf9 and Fgf20 null (Fgf9^LacZ/LacZ and Fgf20^{Cre.GFP/Cre.GFP}) mice during development. At E18.5, Fgf9^LacZ/LacZ stomachs were hypoplastic, lacking the squamous forestomach. No changes to glandular stomach differentiation were observed using representative markers of glandular lineages. Fgf9^LacZ/LacZ stomachs were smaller during early development (E12.5 and E15.5). RNA-seq analysis of Fgf9^LacZ/LacZ mice at E15.5 showed that squamous-epithelium-associated transcripts were underrepresented, and glandular epithelial transcripts were overrepresented. Analysis of gastric patterning at E12.5 revealed loss of early squamous progenitors in the epithelium, characterized by loss of SOX2⁺; GATA4^- cells. We further show that loss of Fgf20 does not alone impact gastric development nor modify the Fgf9^LacZ/LacZ phenotype.

Conclusions: Fgf9 drives gastric growth and squamous epithelial identity during gastric development.