TFAM is required for maturation of the fetal and adult intestinal epithelium

Manasa Srivillibhuthur, Bailey N. Warder, Natalie H. Toke, Pooja P. Shah, Qiang Feng, Nan Gao, Edward M. Bonder, Michael P. Verzi

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

During development, the embryo transitions from a metabolism favoring glycolysis to a metabolism favoring mitochondrial respiration. How metabolic shifts regulate developmental processes, or how developmental processes regulate metabolic shifts, remains unclear. To test the requirement of mitochondrial function in developing endoderm-derived tissues, we genetically inactivated the mitochondrial transcription factor, Tfam, using the Shh-Cre driver. Tfam mutants did not survive postnatally, exhibiting defects in lung development. In the developing intestine, TFAM-loss was tolerated until late fetal development, during which the process of villus elongation was compromised. While progenitor cell populations appeared unperturbed, markers of enterocyte maturation were diminished and villi were blunted. Loss of TFAM was also tested in the adult intestinal epithelium, where enterocyte maturation was similarly dependent upon the mitochondrial transcription factor. While progenitor cells in the transit amplifying zone of the adult intestine remained proliferative, intestinal stem cell renewal was dependent upon TFAM, as indicated by molecular profiling and intestinal organoid formation assays. Taken together, these studies point to critical roles for the mitochondrial regulator TFAM for multiple aspects of intestinal development and maturation, and highlight the importance of mitochondrial regulators in tissue development and homeostasis.

Original languageEnglish (US)
Pages (from-to)92-101
Number of pages10
JournalDevelopmental Biology
Volume439
Issue number2
DOIs
StatePublished - Jul 15 2018

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Keywords

  • Intestinal development
  • Intestinal stem cells
  • Mitochondria
  • TFAM

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