A view of amphibian embryology during the last century.

Having started working in the field of amphibian embryology over 50 years ago, I make some comments about the changes that seem to me to have taken place in this field over this period. Over the period 1885 to 1960, much of the highly regarded experimental embryology was conducted on amphibian eggs and embryos. Indeed, much of this work was conducted in Germany and Switzerland using eggs and embryos of European newts (salamanders) and frogs of the Rana group. Xenopus started to be used extensively after the 1950s because eggs and embryos could be obtained throughout the year by hormone injection and because sexually mature animals could be raised from an egg within one year. Since the 1960s, publications using Xenopus have exceeded those using other amphibian species by 100-fold. This short commentary highlights some of the major advances attributable to embryological work with Amphibia and exemplifies these advances by reference to those who have made conspicuous contributions in this area.This is the final version. It was first published by UBC Press at http://www.ijdb.ehu.es/web/paper/150111jg/a-view-of-amphibian-embryology-during-the-last-century

TCTP in Development and Cancer

The translationally controlled tumor protein (TCTP) is highly conserved among animal species. It is widely expressed in many different tissues. It is involved in regulating many fundamental processes, such as cell proliferation and growth, apoptosis, pluripotency, and the cell cycle. Hence, it is not surprising that it is essential for normal development and, if misregulated, can lead to cancer. Provided herein is an overview of the diverse functions of TCTP, with a focus on development. Furthermore, we discuss possible ways by which TCTP misregulation or mutation could result in cancer

Histone H3 lysine 4 methylation is associated with the transcriptional reprogramming efficiency of somatic nuclei by oocytes.

BACKGROUND: When the nuclei of mammalian somatic cells are transplanted to amphibian oocytes in the first meiotic prophase, they are rapidly induced to begin transcribing several pluripotency genes, including Sox2 and Oct4. The more differentiated the donor cells of the nuclei, the longer it takes for the pluripotency genes to be activated after the nuclear transfer to oocytes. We have used this effect in order to investigate the role of histone modifications in this example of nuclear reprogramming. RESULTS: Reverse transcription polymerase chain reaction analysis shows that the transcriptional reprogramming of pluripotency genes, such as Sox2 and Oct4, takes place in transplanted nuclei from C3H10T1/2 cells and from newly differentiated mouse embryonic stem cells. We find that the reprogramming of 10T1/2 nuclei is accompanied by an increased phosphorylation, an increased methylation and a rapidly reduced acetylation of several amino acids in H3 and other histones. These results are obtained by the immunofluorescent staining of transplanted nuclei and by Western blot analysis. We have also used chromatin immunoprecipitation analysis to define histone modifications associated with the regulatory or coding regions of pluripotency genes in transplanted nuclei. Histone phosphorylation is increased and histone acetylation is decreased in several regulatory and gene coding regions. An increase of histone H3 lysine 4 dimethylation (H3K4 me2) is seen in the regulatory regions and gene coding region of pluripotency genes in reprogrammed nuclei. Furthermore, histone H3 lysine 4 trimethylation (H3K4 me3) is observed more strongly in the regulatory regions of pluripotency genes in transplanted nuclei that are rapidly reprogrammed than in nuclei that are reprogrammed slowly and are not seen in beta-globin, a gene that is not reprogrammed. When 10T1/2 nuclei are incubated in Xenopus oocyte extracts, histone H3 serine 10 (H3S10) is strongly phosphorylated within a few hours. Immunodepletion of Aurora B prevents this phosphorylation. CONCLUSION: We conclude that H3K4 me2 and me3 are likely to be important for the efficient reprogramming of pluripotency genes in somatic nuclei by amphibian oocytes and that Aurora B kinase is required for H3S10 phosphorylation which is induced in transplanted somatic cell nuclei.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

TCTP in development and cancer.

The translationally controlled tumor protein (TCTP) is highly conserved among animal species. It is widely expressed in many different tissues. It is involved in regulating many fundamental processes, such as cell proliferation and growth, apoptosis, pluripotency, and the cell cycle. Hence, it is not surprising that it is essential for normal development and, if misregulated, can lead to cancer. Provided herein is an overview of the diverse functions of TCTP, with a focus on development. Furthermore, we discuss possible ways by which TCTP misregulation or mutation could result in cancer.Peer Reviewe

HIRA dependent H3.3 deposition is required for transcriptional reprogramming following nuclear transfer to Xenopus oocytes.

BACKGROUND: Nuclear reprogramming is potentially important as a route to cell replacement and drug discovery, but little is known about its mechanism. Nuclear transfer to eggs and oocytes attempts to identify the mechanism of this direct route towards reprogramming by natural components. Here we analyze how the reprogramming of nuclei transplanted to Xenopus oocytes exploits the incorporation of the histone variant H3.3. RESULTS: After nuclear transplantation, oocyte-derived H3.3 but not H3.2, is deposited on several regions of the genome including rDNA, major satellite repeats, and the regulatory regions of Oct4. This major H3.3 deposition occurs in absence of DNA replication, and is HIRA-and transcription-dependent. It is necessary for the shift from a somatic- to an oocyte-type of transcription after nuclear transfer. CONCLUSIONS: This study demonstrates that the incorporation of histone H3.3 is an early and necessary step in the direct reprogramming of somatic cell nuclei by oocyte. It suggests that the incorporation of histone H3.3 is necessary during global changes in transcription that accompany changes in cell fate.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Epigenetic stability of repressed states involving the histone variant macroH2A revealed by nuclear transfer to Xenopus oocytes

How various epigenetic mechanisms restrict chromatin plasticity to determine the stability of repressed genes is poorly understood. Nuclear transfer to Xenopus oocytes induces the transcriptional reactivation of previously silenced genes. Recent work suggests that it can be used to analyze the epigenetic stability of repressed states. The notion that the epigenetic state of genes is an important determinant of the efficiency of nuclear reprogramming is supported by the differential reprogramming of given genes from different starting epigenetic configurations. After nuclear transfer, transcription from the inactive X chromosome of post-implantation-derived epiblast stem cells is reactivated. However, the same chromosome is resistant to reactivation when embryonic fibroblasts are used. Here, we discuss different kinds of evidence that link the histone variant macroH2A to the increased stability of repressed states. We focus on developmentally regulated X chromosome inactivation and repression of autosomal pluripotency genes, where macroH2A may help maintain the long-term stability of the differentiated state of somatic cells

The myeloid lineage is required for the emergence of a regeneration-permissive environment following Xenopus tail amputation.

Regeneration-competent vertebrates are considered to suppress inflammation faster than non-regenerating ones. Hence, understanding the cellular mechanisms affected by immune cells and inflammation can help develop strategies to promote tissue repair and regeneration. Here, we took advantage of naturally occurring tail regeneration-competent and -incompetent developmental stages of Xenopus tadpoles. We first establish the essential role of the myeloid lineage for tail regeneration in the regeneration-competent tadpoles. We then reveal that upon tail amputation there is a myeloid lineage-dependent change in amputation-induced apoptosis levels, which in turn promotes tissue remodelling, and ultimately leads to the relocalization of the regeneration-organizing cells responsible for progenitor proliferation. These cellular mechanisms failed to be executed in regeneration-incompetent tadpoles. We demonstrate that regeneration incompetency is characterized by inflammatory myeloid cells whereas regeneration competency is associated with reparative myeloid cells. Moreover, treatment of regeneration-incompetent tadpoles with immune-suppressing drugs restores myeloid lineage-controlled cellular mechanisms. Collectively, our work reveals the effects of differential activation of the myeloid lineage on the creation of a regeneration-permissive environment and could be further exploited to devise strategies for regenerative medicine purposes

Sperm is epigenetically programmed to regulate gene transcription in embryos.

For a long time, it has been assumed that the only role of sperm at fertilization is to introduce the male genome into the egg. Recently, ideas have emerged that the epigenetic state of the sperm nucleus could influence transcription in the embryo. However, conflicting reports have challenged the existence of epigenetic marks on sperm genes, and there are no functional tests supporting the role of sperm epigenetic marking on embryonic gene expression. Here, we show that sperm is epigenetically programmed to regulate embryonic gene expression. By comparing the development of sperm- and spermatid-derived frog embryos, we show that the programming of sperm for successful development relates to its ability to regulate transcription of a set of developmentally important genes. During spermatid maturation into sperm, these genes lose H3K4me2/3 and retain H3K27me3 marks. Experimental removal of these epigenetic marks at fertilization de-regulates gene expression in the resulting embryos in a paternal chromatin-dependent manner. This demonstrates that epigenetic instructions delivered by the sperm at fertilization are required for correct regulation of gene expression in the future embryos. The epigenetic mechanisms of developmental programming revealed here are likely to relate to the mechanisms involved in transgenerational transmission of acquired traits. Understanding how parental experience can influence development of the progeny has broad potential for improving human health.We thank: T. Jenuwein and N. Shukeir for anti-H3K27me3 antibody; A. Bannister, J. Ahringer and E. Miska for comments on the manuscript; Gurdon group members for reading the manuscript; The International Xenopus laevis Genome Project Consortium (the Harland, Rokhsar, Taira labs and others) for providing unpublished genome and gene annotation information. M.T. is supported by WT089613 and by MR/K011022/1. V.G. and P.Z. are funded by AICR 10-0908. A.S. is supported by MR/K011022/1. K.M. is a Research Fellow at Wolfson College and is supported by the Herchel Smith Postdoctoral Fellowship. E.M.M. is supported by National Institutes of Health, National Science Foundation, Cancer Prevention Research Institute of Texas, and the Welch Foundation (F1515). J.J. and J.B.G. are supported by WT101050/Z/13/Z. S.E. acknowledges Boehringer Ingelheim Fond fellowship. A.H.F.M.P. is supported by the Swiss National Science Foundation (31003A_125386) and the Novartis Research Foundation. All members of the Gurdon Institute acknowledge the core support provided by CRUK C6946/A14492 and WT092096.This is the final version of the article. It first appeared from Cold Spring Harbor Laboratory Press via https://doi.org/10.1101/gr.201541.11

Histone variant macroH2A confers resistance to nuclear reprogramming

Gurdon and collaborators report reversible X chromosome inactivation in epiblast stem cells (EpiSCs) that seems to be determined by macroH2A1 deposition. These findings are of rather general interest as they highlight the epigenetic state of repressed loci as determinant for reprogramming efficiency

Deficient Induction Response in a Xenopus Nucleocytoplasmic Hybrid

Defects in induction signaling and response underlie the nucleocytoplasmic incompatibility between two evolutionarily distant frog species, while specific treatments partially restore this response in explants and whole embryos