Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia

Sophie Patzek; Zhe Liu; Sean de la O; Sean Chang; Lauren E. Byrnes; Xiuqin Zhang; David M. Ornitz; Julie B. Sneddon

iScience (Apr 2023)

Loss of Fgf9 in mice leads to pancreatic hypoplasia and asplenia

Sophie Patzek,
Zhe Liu,
Sean de la O,
Sean Chang,
Lauren E. Byrnes,
Xiuqin Zhang,
David M. Ornitz,
Julie B. Sneddon

Affiliations

Sophie Patzek: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Endocrinology and Metabolism, University of California, San Francisco, San Francisco, CA 94143, USA
Zhe Liu: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Sean de la O: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Sean Chang: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Lauren E. Byrnes: Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
Xiuqin Zhang: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA
David M. Ornitz: Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA
Julie B. Sneddon: Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Corresponding author

Journal volume & issue: Vol. 26, no. 4
p. 106500

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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