Transcription factors that shape the mammalian pancreas

Diabetologia. 2020 Oct;63(10):1974-1980. doi: 10.1007/s00125-020-05161-0. Epub 2020 Sep 7.


Improving our understanding of mammalian pancreas development is crucial for the development of more effective cellular therapies for diabetes. Most of what we know about mammalian pancreas development stems from mouse genetics. We have learnt that a unique set of transcription factors controls endocrine and exocrine cell differentiation. Transgenic mouse models have been instrumental in studying the function of these transcription factors. Mouse and human pancreas development are very similar in many respects, but the devil is in the detail. To unravel human pancreas development in greater detail, in vitro cellular models (including directed differentiation of stem cells, human beta cell lines and human pancreatic organoids) are used; however, in vivo validation of these results is still needed. The current best 'model' for studying human pancreas development are individuals with monogenic forms of diabetes. In this review, we discuss mammalian pancreas development, highlight some discrepancies between mouse and human, and discuss selected transcription factors that, when mutated, cause permanent neonatal diabetes. Graphical abstract.

Keywords: Development; Human; Islets of Langerhans; Mouse; NEUROG3; Neonatal diabetes; Neurogenin 3; PDX1; Pancreas and duodenal homeobox 1; RFX6; Regulatory factor X6; Review; Transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Line
  • Diabetes Mellitus / genetics
  • Gene Expression Regulation, Developmental / genetics*
  • Humans
  • In Vitro Techniques
  • Insulin-Secreting Cells
  • Mice
  • Organoids
  • Pancreas / embryology*
  • Pancreas / metabolism
  • Pluripotent Stem Cells
  • Transcription Factors / genetics*


  • Transcription Factors

Supplementary concepts

  • Diabetes Mellitus, Permanent Neonatal