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Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia.

ABSTRACT: Pancreatic development requires spatially and temporally controlled expression of growth factors derived from mesenchyme. Here, we report that in mice the secreted factor Fgf9 is expressed principally by mesenchyme and then mesothelium during early development, then subsequently by both mesothelium and rare epithelial cells by E12.5 and onwards. Global knockout of the Fgf9 gene resulted in the reduction of pancreas and stomach size, as well as complete asplenia. The number of early Pdx1+ pancreatic progenitors was reduced at E10.5, as was proliferation of mesenchyme at E11.5. Although loss of Fgf9 did not interfere with differentiation of later epithelial lineages, single-cell RNA-Sequencing identified transcriptional programs perturbed upon loss of Fgf9 during pancreatic development, including loss of the transcription factor Barx1. Lastly, we identified conserved expression patterns of FGF9 and receptors in human fetal pancreas, suggesting that FGF9 expressed by pancreatic mesenchyme may similarly affect the development of the human pancreas.

SUBMITTER: Patzek S

PROVIDER: S-EPMC10121468 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia.

Patzek Sophie S Liu Zhe Z de la O Sean S Chang Sean S Byrnes Lauren E LE Zhang Xiuqin X Ornitz David M DM Sneddon Julie B JB

iScience 20230325 4

Pancreatic development requires spatially and temporally controlled expression of growth factors derived from mesenchyme. Here, we report that in mice the secreted factor Fgf9 is expressed principally by mesenchyme and then mesothelium during early development, then subsequently by both mesothelium and rare epithelial cells by E12.5 and onwards. Global knockout of the <i>Fgf9</i> gene resulted in the reduction of pancreas and stomach size, as well as complete asplenia. The number of early Pdx1+ ...[more]

PMID: 37096042

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Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia.

Publications

Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia.

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