In the present review the authors discussed the identification of selector, or …

• Abstract
• Introduction
• Identification of master switch genes and MyoD
• Transdifferentiation of myoblasts to adipocytes
• In vivo pancreas to liver transdifferentiation
• Conversion of hepatic cells to pancreatic-like cells
• Transdifferentiation of liver to pancreas by ectopic expression of Pdx1
• Hes1 as a suppressor of Ngn3
• Wnt signalling
• Barrett's metaplasia
• Bone marrow transdifferentiation - fact or artefact?
• Summary
• References
• Figures

Biology Articles » Developmental Biology » The molecular basis of transdifferentiation » Conversion of hepatic cells to pancreatic-like cells

Conversion of hepatic cells to pancreatic-like cells

- The molecular basis of transdifferentiation

Although experimentally less well documented, recent progress in our understanding of the molecular biology of pancreatic development has taken us several steps closer to elucidating the mechanisms involved in the switch from hepatic to pancreatic cell types. Studies using mouse knockouts have demonstrated that certain transcription factors are essential for the steps in β cell formation: first the specification of a pancreatic rudiment in the endodermal epithelium, then the formation of endocrine precursor cells and finally the commitment to the β cell phenotype [28–30]. In the mouse embryo, a single inductive signal, fibroblast growth factor (FGF), distinguishes the region of endoderm that becomes the liver bud from that destined to become the ventral pancreatic bud [31], suggesting that only one or a few transcription factors need to have their activity switched on or off in order to interconvert the two tissues. Candidate transcription factors acting as master switch genes to determine a pancreatic fate are Pdx1, Ngn3, PTF1-p48 and Hes1.

Pdx1 and Ngn3

Two transcription factors known to be particularly important in the normal development of β cells are Pdx1 and Ngn3. Pdx1 is a homeodomain-containing transcription factor expressed in the early pancreatic buds and surrounding duodenum [32]. All pancreatic precursor cells express Pdx1 at an early stage of development [33], however expression later becomes restricted to β cells where Pdx1 is a specific transcription factor required for the expression of insulin. Interestingly, if the Pdx1 gene is knocked out, pancreatic agenesis results [32, 34], implicating Pdx1 as an essential factor in the determination of the pancreatic cell fate.