School of Medicine, Deakin University, Pigdons Road, Geelong, VIC, Australia.
Peter MacCallum Cancer Centre, Melbourne, Australia.
BMC Genomics. 2018 Oct 5;19(1):732. doi: 10.1186/s12864-018-5102-2.
After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray short-tailed opossum (Monodelphis domestica).
Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis.
The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung.
有袋类动物经过短暂的妊娠期，产下肺部尚未完全发育成熟的早产儿，在生命早期，幼崽部分依赖皮肤进行气体交换。因此，与人类和小鼠等真兽类哺乳动物不同，有袋类动物的肺部主要在出生后发育。为了探讨有袋类动物与真兽类动物肺部发育的机制，对灰色短尾负鼠（Monodelphis domestica）进行了形态学和基因表达分析。
Monodelphis 的产后肺发育经历了三个关键的发育阶段：（i）从晚期小管到早期囊泡的过渡阶段，（ii）囊泡和（iii）肺泡阶段，与真兽类动物中重叠胚胎和围产期的发育阶段相似。鉴定出差异表达的基因，并与发育阶段相关联。功能类别包括生长因子、细胞外基质蛋白（ECMs）、转录因子和与分支形态发生、肺泡发生和血管生成相关的信号通路。与发表在小鼠上的数据进行比较，突出了细胞外基质重塑和信号通路（如 Wnt、Notch、IGF、TGFβ、视黄酸和血管生成素）的保守重要性。比较还揭示了与肺泡发生和出生相关的哺乳动物基因表达程序的变化，这表明真兽类小鼠无功能的胚胎肺和有袋类 Monodelphis 早产儿部分功能的发育肺之间存在细微差异。这些数据还突出了一组在肺泡发生期间和之后在 Monodelphis 中特异性表达的收缩蛋白。
研究结果提供了对有袋类动物肺部发育的深入了解，并支持了有袋类动物出生后发育模型在更好地理解哺乳动物支气管肺泡肺的进化方面的潜力。
