Biologie cellulaire et du développement
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Unraveling the Myth of Foxa2 in Endocrine Formation of the Pancreatic Lineages

Willmann SJ

Diabetes mellitus is a severe disease caused by the autoimmune destruction and/or secreting defects of the β-cells with a global prognosis of 844 million patients in the next 20 years (The World Health Organization). The differences are stated either as T1D (Type1 Diabetes) or T2D (Type 2 Diabetes), focusing on the occurrence of the disease itself and the inheritance either early in life, at the beginning of the adulthood or in adults. Further studies are progressively made in the process of pregnancy, where a specific subset of diabetes appears for the expectant mother. Thus, making the disease itself a complex challenge in the world health population and on focus in the field of Research and Development. The focus is driven by elucidating the different factors in the maturation steps of the pancreatic insulin-secreting β-cell, impairment in this β-cells lead either to T1D or T2D. The main factor which accelerates the progression of the developing pancreas suggests being the fork head box (Fox) gene Foxa2, targeted deletions of Foxa2 in mice led to increased adiposity on a high-fat diet and decreased adipocyte glucose uptake and glycolysis. Interestingly, the null allele of Foxa2 leads to severe defects in embryogenesis and death at the embryonic stage (E) 10-11, suggesting an important role in the process of organogenesis. Thereby, Foxa2 and its target genes may shed light in specifically elucidating the transcriptional and signaling network which drives the lineage formation within the pancreas and suggests to be a promising target for creating the β-cell in vivo. Insights into the unique expression of Foxa2 in pancreatic organogenesis will accelerate our understanding of pancreatic development and highlight current findings in the field of diabetes.