Cellular and molecular drivers of differential organ growth: insights from the limbs of Monodelphis domestica
Cellular and molecular drivers of differential organ growth: insights from the limbs of Monodelphis domestica
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DOI：
10.1007/s00427-016-0549-0
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发表时间：
2016-06-01
影响因子：
2.4
通讯作者：
Sears, Karen E.
中科院分区：
文献类型：
--
作者：
Dowling, Anna;Doroba, Carolyn;Sears, Karen E.
生物学中的一个基本问题是“在发育过程中，生长是如何受到不同的调节以产生特定大小的器官的？“我们使用了一种新的模型系统来研究器官的差异生长，即负鼠的四肢，以研究哺乳动物器官差异生长的细胞和分子基础。负鼠的前肢比后肢长得快得多，这使得负鼠的四肢成为研究差异生长的一个特殊系统。我们首先利用负鼠前肢和后肢生长的巨大差异来识别差异肢体生长的细胞过程和分子信号。然后，我们使用器官培养和FGF配体和抑制剂的药理学添加来测试FGF/促分裂原活化蛋白激酶（MAPK）信号通路在驱动这些细胞过程中的作用。我们发现，来自肢体内的分子信号驱动细胞增殖的差异，这有助于负鼠前肢和后肢的差异生长。我们还发现，Fgf/MAPK通路的改变可以产生细胞增殖的差异，反映了野生型前肢和后肢的负鼠和Fgf/MAPK信号的操纵影响下游的粘着斑细胞外基质（FA-ECM）和Wnt信号在负鼠肢体之间观察到的差异。总之，这些发现表明，FGF/MAPK通路的进化变化可能有助于推动所观察到的负鼠前肢和后肢细胞行为和生长差异。
A fundamental question in biology is "how is growth differentially regulated during development to produce organs of particular sizes?" We used a new model system for the study of differential organ growth, the limbs of the opossum (Monodelphis domestica), to investigate the cellular and molecular basis of differential organ growth in mammals. Opossum forelimbs grow much faster than hindlimbs, making opossum limbs an exceptional system with which to study differential growth. We first used the great differences in opossum forelimb and hindlimb growth to identify cellular processes and molecular signals that underlie differential limb growth. We then used organ culture and pharmacological addition of FGF ligands and inhibitors to test the role of the Fgf/Mitogen-activated protein kinases (MAPK) signaling pathway in driving these cellular processes. We found that molecular signals from within the limb drive differences in cell proliferation that contribute to the differential growth of the forelimb and hindlimbs of opossums. We also found that alterations in the Fgf/MAPK pathway can generate differences in cell proliferation that mirror those observed between wild-type forelimb and hindlimbs of opossums and that manipulation of Fgf/MAPK signaling affects downstream focal adhesion-extracellular matrix (FA-ECM) and Wnt signaling in opossum limbs. Taken together, these findings suggest that evolutionary changes in the Fgf/MAPK pathway could help drive the observed differences in cell behaviors and growth in opossum forelimb and hindlimbs.