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

Developmental biology

Pooja P. Shah^1¹  Natalie H. Toke^1²  Bailey N. Warder^1³  Manasa Srivillibhuthur^1,3⁴ 

[1] Department of Biological Sciences, Rutgers, The State University of New Jersey, Newark, NJ 07102, USA^4;Lewis Katz School of Medicine at Temple University, 3500 N Broad Street, Philadelphia, PA 19140, USA^3;Rutgers Cancer Institute of New Jersey (CINJ), 195 Little Albany Street, New Brunswick, NJ 08903, USA^2;Rutgers University, Department of Genetics, Human Genetics Institute of New Jersey (HGINJ), 145 Bevier Road, Piscataway Township, NJ 08854, USA^1

关键词: TFAM;    Mitochondria;    Intestinal development;    Intestinal stem cells;   

DOI  :  10.1016/j.ydbio.2018.04.015

学科分类：生物科学（综合）

来源: Academic Press

【 摘 要 】

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.

【 授权许可】

CC BY