Diverse gene expression and function of semaphorins in developing lung: positive and negative regulatory roles of semaphorins in lung branching morphogenesis
Diverse gene expression and function of semaphorins in developing lung: positive and negative regulatory roles of semaphorins in lung branching morphogenesis
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DOI：
10.1046/j.1365-2443.2001.00441.x
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发表时间：
2001-06-01
期刊：
影响因子：
2.1
通讯作者：
Goshima, Y
中科院分区：
文献类型：
--
作者：
Kagoshima, M;Ito, T;Goshima, Y
背景：之前，我们报道了 Sema3A（一种分泌性排斥性轴突引导分子）、CRMP（胶原蛋白反应介导蛋白）-2（一种假定的 Sema3A 细胞内信号分子）和 Sema3A 受体神经毡蛋白-1 在发育中的肺中表达。 Sema3A抑制器官培养中胚胎肺的分支形态发生。结果：通过原位杂交检测了Sema3A、Sema3C、Sema3F及其受体NP-1、NP-2和plexin-A1的基因表达。从胚胎E11.5到E17.5，在小鼠肺中检测到所有六个基因的转录本，酸显示出高度特异性的时空分布，检测到的受体基因的分布模式与信号蛋白的已知受体使用一致。与Sema3A相反，我们发现其他3类信号蛋白Sema3C和Sema3F刺激分支形态发生。 Sema3C 或 Sema3F 的这种刺激作用伴随着末端上皮细胞中溴脱氧尿苷 (BrdU) 掺入 DNA 的适度增加。结论：不同信号蛋白及其受体的协调表达模式，以及影响分支形态发生的特定活性表明，信号蛋白在发育中的肺中充当分支形态发生的正向和负向调节剂。
Background: Previously, we reported that Sema3A, one of the secreted repulsive axon guidance molecules, CRMP (collaprin response mediator protein)-2, a putative intracellular signalling molecule for Sema3A and Sema3A receptor neuropilin-1 are expressed in the developing lung. Sema3A inhibits branching morphogenesis of embryonic lung in organ culture.Results: We examined the gene expression of Sema3A, Sema3C, Sema3F and their receptors, NP-1, NP-2 and plexin-A1 by in situ hybridization. Transcripts of all six genes were detected in mouse lung from embryonic day E11.5 to E17.5, acid displayed highly specific spatiotemporal distributions, The distribution of the receptor genes was detected in patterns which were consistent with known receptor usage of the semaphorins, In contrast to Sema3A, we found that the other class 3 semaphorins, Sema3C and Sema3F, stimulated branching morphogenesis. This stimulatory effect of Sema3C or Sema3F was accompanied by a moderate increase in the incorporation of bromodeoxyuridine (BrdU) into DNA in the terminal epithelial cells.Conclusion: The coordinated expression patterns of different semaphorins and their receptors, together with the specific activities affecting branching morphogenesis, suggest that the semaphorins act as both positive and negative regulators of branching morphogenesis in the developing lung.