Discontinuities in Rap1 activity determine epithelial cell morphology within the developing wing of Drosophila.

Discontinuities in Rap1 activity determine epithelial cell morphology within the developing wing of Drosophila.
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Rap1 活性的不连续性决定了果蝇发育中翅膀内的上皮细胞形态。

DOI:
10.1016/j.ydbio.2012.06.024
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发表时间:
2012
影响因子:
2.7
通讯作者:
Curtiss,Jennifer
Curtiss,Jennifer
中科院分区:
生物学3区
文献类型:
--
作者:
O'Keefe,DavidD;Gonzalez-Niño,Eduardo;Edgar,BruceA;Curtiss,Jennifer

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控制发育中的上皮细胞命运的机制已经被深入研究,许多关键的细胞间信号通路被识别,并被很好地描述。然而,一旦这些细胞的命运已经确定,人们对驱动这些细胞形态分化的下游事件知之甚少。在果蝇的翼叶上皮中,主要有两种细胞:静脉细胞和脉间细胞。细胞增殖完成后,细胞与细胞间的粘连接触被细化,绝大多数静脉间细胞呈六角形形态。然而,在静脉区域内,细胞形状的细化会产生梯形。区分静脉和静脉间细胞命运的信号事件已被很好地理解,但静脉/静脉间细胞结构差异背后的遗传途径在很大程度上仍未被描述。我们在这里表明,RAP1 GTP酶在决定发育中的翅膀上皮细胞类型特定的形态方面起着关键作用。RAP1与其效应器CANOE一起促进黏附分子DE-钙粘附素在上皮细胞顶端外周的对称分布。我们提供的证据表明,在假定的静脉组织中,RAP1/CANOE活性下调,导致粘连不对称和非六角形细胞形态。特别是,静脉细胞在形态分化时,独木舟的水平会降低。我们还证明了Rap1的过度表达破坏了发育中的上皮细胞和成虫翅膀叶片中的血管形成。因此,静脉/静脉间的形态差异至少部分是由于RAP1活性的模式调节造成的。
Mechanisms that govern cell-fate specification within developing epithelia have been intensely investigated, with many of the critical intercellular signaling pathways identified, and well characterized. Much less is known, however, about downstream events that drive the morphological differentiation of these cells, once their fate has been determined. In the Drosophila wing-blade epithelium, two cell types predominate: vein and intervein. After cell proliferation is complete and adhesive cell–cell contacts have been refined, the vast majority of intervein cells adopt a hexagonal morphology. Within vein territories, however, cell-shape refinement results in trapezoids. Signaling events that differentiate between vein and intervein cell fates are well understood, but the genetic pathways underlying vein/intervein cyto-architectural differences remain largely undescribed. We show here that the Rap1 GTPase plays a critical role in determining cell-type-specific morphologies within the developing wing epithelium. Rap1, together with its effector Canoe, promotes symmetric distribution of the adhesion molecule DE-cadherin about the apicolateral circumference of epithelial cells. We provide evidence that in presumptive vein tissue Rap1/Canoe activity is down-regulated, resulting in adhesive asymmetries and non-hexagonal cell morphologies. In particular Canoe levels are reduced in vein cells as they morphologically differentiate. We also demonstrate that over-expression of Rap1 disrupts vein formation both in the developing epithelium and the adult wing blade. Therefore, vein/intervein morphological differences result, at least in part, from the patterned regulation of Rap1 activity.
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