Axial protocadherin is a mediator of prenotochord cell sorting in Xenopus

Axial protocadherin is a mediator of prenotochord cell sorting in Xenopus
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DOI:
10.1006/dbio.2002.0589
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发表时间:
2002-04-15
影响因子:
2.7
通讯作者:
Asashima, M
Asashima, M
中科院分区:
生物学3区
文献类型:
--
作者:
Kuroda, H;Inui, M;Asashima, M

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脊索前细胞分选被认为是脊索动物早期发育过程中最早的细胞分选事件之一。我们最近证明了这种分选事件发生在体外,尽管这种活性的介质仍未确定。在此,我们报道了轴向原钙粘蛋白(AXPC)的全长cDNA克隆,它是人原钙粘蛋白-1 (PCD1)的同源物。AXPC编码一种跨膜蛋白(AXPC),该蛋白仅在神经期的脊索中表达,在尾芽期的肾原、体、心脏、视泡、耳泡和脑的不同部位表达。细胞分离和再聚集实验和体内显微注射实验表明,过表达一种膜系形式的AXPC (MT-AXPC)的细胞获得了与脊索前细胞相同的粘附特性。此外,微量注射编码AXPC显性阴性形式的mRNA (DN-AXPC)或morpholino寡核苷酸都会干扰脊索前细胞的分选活性和正常轴的形成。该研究表明,AXPC对于原肠胚脊索前细胞的分选是必要和充分的,并且可能介导发育后期的分选事件。(C) 2002 Elsevier Science (USA)。
Prenotochord cell sorting is regarded as one of the first cell sorting events in early chordate development. We recently demonstrated that this sorting event occurs in vitro, although the mediator of this activity remains unidentified. Herein, we report the isolation of a full-length cDNA clone of Axial Protocadherin (AXPC), the homologue of human protocadherin-1 (PCD1). AXPC encodes a transmembrane protein (AXPC) that is expressed exclusively in the notochord at the neurula stage and in the pronephros, somites, heart, optic vesicle, otic vesicle, and distinct parts of the brain at the tailbud stage. Cell dissociation and reaggregation assays and in vivo microinjection experiments demonstrated that cells overexpressing a membrane-tethered form of AXPC (MT-AXPC) acquired the same adhesive properties as prenotochord cells. Moreover, microinjection of either mRNA encoding the dominant negative form of AXPC (DN-AXPC) or morpholino oligonucleotides interferes with the sorting activity of prenotochord cells and normal axis formation. This study suggests that AXPC is necessary and sufficient for prenotochord cell sorting in the gastrulating embryo, and may also mediate sorting events later in development. (C) 2002 Elsevier Science (USA).