Mesenchymal bone morphogenetic protein signaling is required for normal pancreas development.
Mesenchymal bone morphogenetic protein signaling is required for normal pancreas development.
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作者：
Ahnfelt-Rønne J;Ravassard P;Pardanaud-Glavieux C;Scharfmann R;Serup P
胰腺器官发生是由上皮细胞和间充质细胞之间的相互作用协调的，但这些相互作用还没有完全理解。在这里，我们研究了胰腺间充质内骨形态发生蛋白（BMP）信号传导的作用，发现它是间充质和胰腺上皮正常发育所必需的。我们通过磷酸化Smad1，5，8的免疫染色分析了活性BMP信号传导，并测试了在鸡和小鼠胰腺中表达Noggin和显性阴性BMP受体后，胰腺发育是否受到BMP抑制的影响。内源性BMP信号传导仅限于早期胰腺中的间充质，BMP信号传导的抑制导致严重的胰腺发育不全伴上皮分支减少。值得注意的是，当间充质BMP信号传导被阻断时，我们还观察到过度的内分泌分化，推测是继发于有缺陷的间充质至上皮信号传导。我们的结论是，BMP信号在间充质中起着一个以前未被怀疑的作用，需要正常发育的间充质以及上皮。
Pancreas organogenesis is orchestrated by interactions between the epithelium and the mesenchyme, but these interactions are not completely understood. Here we investigated a role for bone morphogenetic protein (BMP) signaling within the pancreas mesenchyme and found it to be required for the normal development of the mesenchyme as well as for the pancreatic epithelium. We analyzed active BMP signaling by immunostaining for phospho-Smad1,5,8 and tested whether pancreas development was affected by BMP inhibition after expression of Noggin and dominant negative BMP receptors in chicken and mouse pancreas. Endogenous BMP signaling is confined to the mesenchyme in the early pancreas and inhibition of BMP signaling results in severe pancreatic hypoplasia with reduced epithelial branching. Notably, we also observed an excessive endocrine differentiation when mesenchymal BMP signaling is blocked, presumably secondary to defective mesenchyme to epithelium signaling. We conclude that BMP signaling plays a previously unsuspected role in the mesenchyme, required for normal development of the mesenchyme as well as for the epithelium.