Review

Cellular and Molecular Life Sciences CMLS

, Volume 63, Issue 19, pp 2317-2328

First online:

The Foxa family of transcription factors in development and metabolism

  • J. R. FriedmanAffiliated withDivision of Gastroenterology and Nutrition, Department of Pediatrics, University of Pennsylvania School of Medicine, Abramson Research Center
  • , K. H. KaestnerAffiliated withDepartment of Genetics and Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine Email author 

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Abstract.

The Foxa subfamily of winged helix/forkhead box (Fox) transcription factors has been the subject of genetic and biochemical study for over 15 years. During this time its three members, Foxa1, Foxa2 and Foxa3, have been found to play important roles in multiple stages of mammalian life, beginning with early development, continuing during organogenesis, and finally in metabolism and homeostasis in the adult. Foxa2 is required for the formation of the node and notochord, and in its absence severe defects in gastrulation, neural tube patterning, and gut morphogenesis result in embryonic lethality. Foxa1 and Foxa2 cooperate to establish competence in foregut endoderm and are required for normal development of endoderm-derived organs such as the liver, pancreas, lungs, and prostate. In post-natal life, members of the Foxa family control glucose metabolism through the regulation of multiple target genes in the liver, pancreas, and adipose tissue. Insight into the unique molecular basis of Foxa function has been obtained from recent genetic and genomic data, which identify the Foxa proteins as ‘pioneer factors’ whose binding to promoters and enhancers enable chromatin access for other tissue-specific transcription factors.

Keywords.

Transcription factors development organogenesis metabolism diabetes