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Abstract：
A common question in organ regeneration is the extent to which regeneration recapitulates embryonic development. To investigate this concept, we compared the expression of two highly interlinked and essential genes for salivary gland development, Sox9 and Fgf10, during submandibular gland development, homeostasis and regeneration. Salivary gland duct ligation/deligation model was used as a regenerative model. Fgf10 and Sox9 expression changed during regeneration compared to homeostasis, suggesting that these key developmental genes play important roles during regeneration, however, significantly both displayed different patterns of expression in the regenerating gland compared to the developing gland. Regenerating glands, which during homeostasis had very few weakly expressing Sox9-positive cells in the striated/granular ducts, displayed elevated expression of Sox9 within these ducts. This pattern is in contrast to embryonic development, where Sox9 expression was absent in the proximally developing ducts. However, similar to the elevated expression at the distal tip of the epithelium in developing salivary glands, regenerating glands displayed elevated expression in a subpopulation of acinar cells, which during homeostasis expressed Sox9 at lower levels. A shift in expression of Fgf10 was observed from a widespread mesenchymal pattern during organogenesis to a more limited and predominantly epithelial pattern during homeostasis in the adult. This restricted expression in epithelial cells was maintained during regeneration, with no clear upregulation in the surrounding mesenchyme, as might be expected if regeneration recapitulated development. As both Fgf10 and Sox9 were upregulated in proximal ducts during regeneration, this suggests that the positive regulation of Sox9 by Fgf10, essential during development, is partially reawakened during regeneration using this model. Together these data suggest that developmentally important genes play a key role in salivary gland regeneration but do not precisely mimic the roles observed during development.
摘要：
器官再生中的一个常见问题是再生在多大程度上概括了胚胎发育。为了研究这个概念，我们比较了唾液腺发育的两个高度互连和必需基因的表达，Sox9和Fgf10，在颌下腺发育过程中，稳态和再生。唾液腺导管结扎/分离模型用作再生模型。与稳态相比，Fgf10和Sox9表达在再生过程中发生变化，表明这些关键的发育基因在再生过程中起着重要的作用，然而,与发育中的腺体相比，两者在再生腺体中的表达模式显着不同。再生腺体,在体内平衡期间，条纹/颗粒导管中很少有弱表达Sox9阳性细胞，在这些导管内显示Sox9的表达升高。这种模式与胚胎发育相反，在近端发育的导管中没有Sox9表达。然而,类似于在发育中的唾液腺中上皮远端尖端的升高表达，再生腺体在腺泡细胞亚群中表达升高，在稳态期间，Sox9的表达水平较低。观察到Fgf10的表达从器官发生过程中广泛的间充质模式转变为成人稳态过程中更有限且主要是上皮模式。这种在上皮细胞中的限制性表达在再生过程中得以维持,周围的间充质没有明显的上调，如果再生概括发展，这可能是预期的。由于Fgf10和Sox9在再生过程中在近端管道中上调，这表明Fgf10对Sox9的正向调节是发育过程中必不可少的，使用此模型在再生过程中部分重新唤醒。这些数据共同表明，发育重要的基因在唾液腺再生中起关键作用，但不能精确模拟发育过程中观察到的作用。
