Positional cloning of heart and soul reveals multiple roles for PKCλ in zebrafish organogenesis
Positional cloning of heart and soul reveals multiple roles for PKCλ in zebrafish organogenesis
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DOI：
10.1016/s0960-9822(01)00458-4
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发表时间：
2001-10-02
期刊：
影响因子：
9.2
通讯作者：
Abdelilah-Seyfried, S
中科院分区：
文献类型：
--
作者：
Horne-Badovinac, S;Lin, D;Abdelilah-Seyfried, S
背景：Par-3/Par-6/aPKC复合物是许多系统中细胞极性的关键调节因子。在果蝇中，这种复合物作用于粘附小带（粘附连接）以建立上皮极性，并有助于在不对称成神经细胞分裂期间定向有丝分裂纺锤体。在MDCKII细胞中，该复合物定位于悬韧带。闭合（紧密连接），并似乎调节上皮极性。然而，在脊椎动物胚胎发生过程中，这种复杂的体内作用是未知的，由于缺乏相关的mutations.Results：我们已经定位克隆斑马鱼的心脏和灵魂（有）突变，这影响了几个胚胎组织的形态发生，并显示它编码非典型蛋白激酶C λ（aPKC λ）。我们发现aPKC λ的缺失影响视网膜、神经管和消化道极化上皮中粘附小带的形成和维持，导致新的表型，例如在发育中的肠中形成多个管腔。此外，突变体显示肠循环和内胚层器官形态发生的缺陷，似乎是独立的上皮极性的缺陷。最后，我们发现，aPKC λ的损失导致缺陷的纺锤体方向在神经retina.Conclusions祖细胞分裂过程中：我们的研究结果表明，aPKC λ是必要的小带的形成和维护。在脊椎动物的早期上皮发育过程中的adherens，并证明了以前未描述的，但在器官形态发生这种蛋白质的关键作用。此外，我们的研究确定了脊椎动物中第一个调节细胞分裂方向的遗传位点。
Background: The Par-3/Par-6/aPKC complex is a key regulator of cell polarity in a number of systems. In Drosophila, this complex acts at the zonula adherens (adherens junctions) to establish epithelial polarity and helps to orient the mitotic spindle during asymmetric neuroblast divisions. In MDCKII cells, this complex localizes to the zonula. occludens (tight junctions) and appears to regulate epithelial polarity. However, the in vivo role of this complex during vertebrate embryogenesis is not known, due to the lack of relevant mutations.Results: We have positionally cloned the zebrafish heart and soul (has) mutation, which affects the morphogenesis of several embryonic tissues, and show that it encodes atypical protein kinase C lambda (aPKC lambda). We find that loss of aPKC lambda affects the formation and maintenance of the zonula adherens in the polarized epithelia of the retina, neural tube, and digestive tract, leading to novel phenotypes, such as the formation of multiple lumens in the developing intestine. In addition, has mutants display defects in gut looping and endodermal organ morphogenesis that appear to be independent of the defects in epithelial polarity. Finally, we show that loss of aPKC lambda leads to defects in spindle orientation during progenitor cell divisions in the neural retina.Conclusions: Our results show that aPKC lambda is required for the formation and maintenance of the zonula. adherens during early epithelial development in vertebrates and demonstrate a previously undescribed yet critical role for this protein in organ morphogenesis. Furthermore, our studies identify the first genetic locus regulating the orientation of cell division in vertebrates.