The window period of NEUROGENIN3 during human gestation (original) (raw)

“…Studying the offspring from the Dutch winter famine of 1944-1945 demonstrated that later impairment in insulin secretion and glucose intolerance, but not resistance to insulin action, in non-diabetic individuals correlated to undernutrition up to but not after 32 weeks gestation (de Rooij et al, 2006), a very similar time period to the profile of NEUROG3 expression (Salisbury et al, 2014). Therefore, one would predict that at least some GWA signals for T2D might relate to events during pancreas development, such as progenitor cell proliferation or β-cell differentiation, rather than to functional attributes of adult β-cells.…”

Section: Endocrine Differentiationmentioning

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“…Studying the offspring from the Dutch winter famine of 1944-1945 demonstrated that later impairment in insulin secretion and glucose intolerance, but not resistance to insulin action, in non-diabetic individuals correlated to undernutrition up to but not after 32 weeks gestation (de Rooij et al, 2006), a very similar time period to the profile of NEUROG3 expression (Salisbury et al, 2014). Therefore, one would predict that at least some GWA signals for T2D might relate to events during pancreas development, such as progenitor cell proliferation or β-cell differentiation, rather than to functional attributes of adult β-cells.…”

Section: Endocrine Differentiationmentioning

“…Jennings et al, 2013). NEUROG3 detection peaks around the end of the first trimester and was not detected in human fetuses after 35 wpc (Salisbury et al, 2014). By additional inference from experiments transplanting human fetal pancreas into mouse, NEUROG3 is probably switched off at some point after 26-28 wpc (Capito et al, 2013).…”

Section: Endocrine Differentiationmentioning

“…In mouse, a biphasic transient wave of Ngn3 expression [24] is observed, wherein the second wave corresponds to the secondary transition, an extensive terminal differentiation event in the developing pancreas that peaks at e15.5. In stark contrast, only a single-phase of NGN3 expression is observed in human that starts at 8wpc (corresponding to e16 in the mouse) and peaks in the second trimester between 10-14wpc[25] (Fig. 1).…”

Section: Section Ii: Early Pancreas Development: From Foregut To Endomentioning

“…Shortly after Neurog3 expression, endocrine cells delaminate from the ductal epithelium and aggregate to form nascent islets. Although there is a transient peak in NEUROG3 expression in human fetal pancreas that corresponds to the stage of endocrine lineage commitment, inactivating mutations of NEUROG3 in humans causes relatively mild defects in endocrine islet cell development and function[43–46]. Interestingly, despite the remarkable molecular conservation between zebrafish and murine pancreas development, Neurog3 is also dispensable for endocrine lineage differentiation in zebrafish and, instead, the control of endocrine cell fate requires two basic helix-loop-helix factors, Ascl1b and Neurod1[47].…”

Section: Endocrine Islet Developmentmentioning