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 » Hes1 as a suppressor of Ngn3

Hes1 as a suppressor of Ngn3

- The molecular basis of transdifferentiation

Hes1 encodes a bHLH transcription factor that acts as a transcriptional repressor of genes such as Ngn3 [51]. Hes1 is required for normal repression of neurogenic programming and expansion of neuronal progenitors [52]. More recently, analysis of Hes1-/- animals has suggested that Hes1 may have a role in repressing endocrine cell development [53]. The elevated expression of Ngn3 in the stomach, small and large intestine in Hes1-/- mice confirmed that Hes1 and Ngn3 counteract in the determination of endocrine cell fate [54]. Based on the pro-endocrine action of Ngn3, the impaired expression of Hes1 would therefore be predicted to influence the differentiation of certain cell types such as pancreatic endocrine cells. To further support this idea, conversion of the developing biliary system to pancreatic tissue in Hes1 deficient mice has recently been described [54, 55]. The experiments also claimed that the conversion from biliary system to pancreatic-like cells might be through the re-activation of Ngn3 that is initially restrained by Hes1.

Intestine in the lung

During development, the lung arises as an outgrowth of the ventral foregut endoderm, a little later than the appearance of the liver (around E9- 9.5 in the mouse) [56]. The developing foregut tube separates to form (1) the future oesophagus and (2) the trachea that bifurcates to give rise to two ventrolateral buds that will become the bronchi. Following a period of morphogenesis involving extensive branching the typical 'treelike' structure characteristic of the lungs emerges and differentiation of the lung epithelia gives rise to several specialised pulmonary cell types; ciliated cells, mucus secreting goblet cells, pulmonary neuroendocrine cells, Clara cells and the alveolar type 1 and type 2 pneumocytes. The signalling events that mediate branching of the lung epithelia are now relatively well understood and involve interplay between FGF and Sonic hedgehog (Shh) pathways [57]. In contrast, the mechanisms regulating determination of the different cell lineages within the lung are not clear. There is some evidence to suggest that development along the pulmonary neuroendocrine lineage requires expression of the Achaete-scute homolog-1, Mash1 [58], whereas Hes1 (Notch signalling pathway) may be involved in the generation of non-neuroendocrine cell types [59, 60]