Gastric hypoplasia in mice lacking fibroblast growth factor 9

IF 1.5 3区生物学 Q2 ANATOMY & MORPHOLOGY Developmental Dynamics Pub Date : 2025-03-01 DOI:10.1002/dvdy.70000

Jason C. Mills, Nattapon Thanintorn, Yongjun Yin, Helen McNeill, David M. Ornitz, Spencer G. Willet

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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.

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缺乏成纤维细胞生长因子9的小鼠胃发育不全。

背景：成纤维细胞生长因子9 （Fgf9）及其平行体Fgf20在发育中的胃中表达。我们利用零等位基因的组合来研究这些生长因子在胃发育过程中的作用。结果：表达数据库分析显示，Fgf9早在E8.5时就在胃内胚层及周围中胚层如间皮中表达，Fgf20在腺胃的胃祖细胞中表达。为了探究Fgf9和Fgf20是否在胃发育中起重要作用，我们检测了Fgf9和Fgf20 null （Fgf9LacZ/LacZ和Fgf20Cre.GFP/Cre.GFP）小鼠发育期间的胚胎胃。E18.5时，Fgf9LacZ/LacZ胃发育不全，缺少鳞状前胃。使用腺系的代表性标记未观察到腺胃分化的变化。Fgf9LacZ/LacZ在发育早期（E12.5和E15.5）胃较小。Fgf9LacZ/LacZ小鼠在E15.5时的RNA-seq分析显示，鳞状上皮相关转录物的代表性不足，而腺上皮转录物的代表性过高。E12.5的胃图分析显示上皮中早期鳞状祖细胞的缺失，其特征是SOX2+的缺失；GATA4 -细胞。我们进一步表明，Fgf20的缺失并不会单独影响胃发育，也不会改变Fgf9LacZ/LacZ表型。结论：Fgf9在胃发育过程中驱动胃的生长和鳞状上皮的特性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Developmental Dynamics 生物-发育生物学

CiteScore

5.10

自引率

8.00%

发文量

116

审稿时长

3-8 weeks

期刊介绍： Developmental Dynamics, is an official publication of the American Association for Anatomy. This peer reviewed journal provides an international forum for publishing novel discoveries, using any model system, that advances our understanding of development, morphology, form and function, evolution, disease, stem cells, repair and regeneration.