Abstract
Xenopus embryos provide a rich source of pluripotent cells that can be differentiated into functional organs. Since the molecular principles of vertebrate organogenesis appear to be conserved between Xenopus and mammals, this system can provide useful guidelines for the directional manipulation of human embryonic stem cells. Pluripotent Xenopus cells can be easily isolated from the animal pole of blastula stage Xenopus embryos. These so called “animal cap” cells represent prospective ectodermal cells, but give rise to endodermal, mesodermal and neuro-ectodermal derivatives if treated with the appropriate factors. These factors include evolutionary conserved modulators of the key developmental signal transduction pathways that can be supplied either by mRNA microinjection or direct application of recombinant proteins. This relatively simple system has added to our understanding of pancreas, liver, kidney, eye and heart development. In particular, recent studies have used animal cap cells to generate ectopic eyes and hearts, setting the stage for future work aimed at programming pluripotent cells for regenerative medicine.
Highlights
Amphibians have traditionally been used as model systems for vertebrate embryogenesis
animal cap cells (ACC) can be turned into endoderm: In a cell-autonomous manner, VegT, a vegetally localizing, maternal T-box transcription factor, or its downstream transcription factor Mixer, can induce the expression of endodermal marker genes [7,8,9]
Transplantation of these programmed ACC into Xenopus embryos, which had undergone bilateral pronephrectomy, suggests that they develop into functional secretory units
Summary
Amphibians have traditionally been used as model systems for vertebrate embryogenesis. During the late 1960s, Peter Nieuwkoop and colleagues discovered that ectodermal cells can differentiate into mesodermal tissue if combined with prospective endodermal cells of the vegetal pole [3] These so-called animal cap cells (ACC) can be isolated from the blastocoel roof of a blastula stage Xenopus embryo. ACC can be turned into endoderm: In a cell-autonomous manner, VegT, a vegetally localizing, maternal T-box transcription factor, or its downstream transcription factor Mixer, can induce the expression of endodermal marker genes [7,8,9] All of these studies using manipulated ACC were primarily based on the analysis of the activation of germ layer-/tissue-specific marker gene expression, as analyzed by either RT-PCR or whole mount in situ hybridization based techniques. Xenopus embryos where they generated organ specific cell types or functional organs (see the following paragraphs on individual organ systems, and for a recent review [10]). The discovery of the ACC as a source for pluripotent precursor cells, which can be directed to differentiate into a broad variety of specialized cell types, has paved the road for their use in the generation of ectopic, functional organs in vivo
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