GON-1 and fibulin have antagonistic roles in control of organ shape
GON-1 and fibulin have antagonistic roles in control of organ shape
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DOI：
10.1016/j.cub.2004.11.006
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发表时间：
2004-11-23
期刊：
影响因子：
9.2
通讯作者：
Kimble, J
中科院分区：
文献类型：
--
作者：
Hesselson, D;Newman, C;Kimble, J
大多数发育中的器官周围都有细胞外基质(ECM)，必须对其进行改造，以适应生长和形态发生。在线虫中，Gon-1 ADAMTS金属蛋白酶同时调节发育中的性腺的伸长和形状[1]。在这里，我们报告了人ADAMTS-4或ADAMTS-9可以替代转基因蠕虫中的Gon-1，这表明人和线虫同源物之间的功能保守。我们进一步确定了纤维蛋白(FBL-1)，一种广泛保守的细胞外基质成分[2]，对性腺形态发生至关重要。FBL-1在非性腺组织中表达，但存在于伸长的性腺表面。纤毛蛋白缺失突变体具有比正常性腺更宽的性腺以及身体大小缺陷。我们发现Gon-1和纤毛蛋白在控制性腺形状方面具有拮抗作用。去除FBL-1，而不是其他ECM成分，可以挽救Gon-1伸长缺陷，去除Gon-1可以挽救FBL-1宽度缺陷。因此，Gon-1蛋白通常会促进组织的伸长和扩张，而纤维蛋白ECM蛋白则会阻止这些关键的形态发生过程。我们认为，在线虫中，Gon-1和纤毛蛋白对器官形状的控制可能为人类类似的细胞过程提供了一个模型，包括血管生成。
Most developing organs are surrounded by an extracellular matrix (ECM), which must be remodeled to accommodate growth and morphogenesis. In C. elegans, the GON-1 ADAMTS metalloprotease regulates both elongation and shape of the developing gonad [1]. Here, we report that either human ADAMTS-4 or ADAMTS-9 can substitute for GON-1 in transgenic worms, suggesting functional conservation between human and nematode homologs. We further identify fibulin (FBL-1), a widely conserved ECM component [2], as critical for gonadal morphogenesis. FBL-1 is expressed in nongonadal tissues but is present at the surface of the elongating gonad. A fibulin deletion mutant has a wider than normal gonad as well as body size defects. We find that GON-1 and fibulin have antagonistic roles in controlling gonadal shape. Depletion of fbl-1, but not other ECM components, rescues gon-1 elongation defects, and removal of gon-1 rescues fbl-1 width defects. Therefore, the GON-1 protease normally promotes tissue elongation and expansion, whereas the fibulin ECM protein blocks these key morphogenetic processes. We suggest that control of organ shape by GON-1 and fibulin in C. elegans may provide a model for similar cellular processes, including vasculogenesis, in humans.