10 Most Recent Papers
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<pubmed limit=5>Frog Development</pubmed>
<pubmed limit=5>Frog Embryology</pubmed>
Anosmin-1 is essential for neural crest and cranial placodes formation in Xenopus
Biochem Biophys Res Commun. 2018 Jan 15;495(3):2257-2263. doi: 10.1016/j.bbrc.2017.12.127. Epub 2017 Dec 22.
Bae CJ1, Hong CS1, Saint-Jeannet JP2.
During embryogenesis vertebrates develop a complex craniofacial skeleton associated with sensory organs. These structures are primarily derived from two embryonic cell populations the neural crest and cranial placodes, respectively. Neural crest cells and cranial placodes are specified through the integrated action of several families of signaling molecules, and the subsequent activation of a complex network of transcription factors. Here we describe the expression and function of Anosmin-1 (Anos1), an extracellular matrix protein, during neural crest and cranial placodes development in Xenopus laevis. Anos1 was identified as a target of Pax3 and Zic1, two transcription factors necessary and sufficient to generate neural crest and cranial placodes. Anos1 is expressed in cranial neural crest progenitors at early neurula stage and in cranial placode derivatives later in development. We show that Anos1 function is required for neural crest and sensory organs development in Xenopus, consistent with the defects observed in Kallmann syndrome patients carrying a mutation in ANOS1. These findings indicate that anos1 has a conserved function in the development of craniofacial structures, and indicate that anos1-depleted Xenopus embryos represent a useful model to analyze the pathogenesis of Kallmann syndrome. KEYWORDS: Anosmin-1; Cranial placode; Kallmann syndrome; Neural crest; Sensory organs; Xenopus
PMID: 29277616 DOI: 10.1016/j.bbrc.2017.12.127
Cloning and spatiotemporal expression of Xenopus laevis Apolipoprotein CI
PLoS One. 2018 Jan 18;13(1):e0191470. doi: 10.1371/journal.pone.0191470. eCollection 2018.
Sridharan J1, Haremaki T1, Weinstein DC1.
Apolipoprotein CI (ApoCI) belongs to the Apolipoprotein superfamily, members of which are involved in lipid transport, uptake and homeostasis. Excessive ApoCI has been implicated in atherosclerosis and Alzheimer's disease in humans. In this study we report the isolation of Xenopus laevis apoCI and describe the expression pattern of this gene during early development, using reverse transcription polymerase chain reaction and whole mount in situ hybridization. Xenopus apoCI is enriched in the dorsal ectoderm during gastrulation, and is subsequently expressed in sensory placodes, neural tube and cranial neural crest. These data suggest as yet uncharacterized roles for ApoCI during early vertebrate embryogenesis. PMID: 29346450 PMCID: PMC5773212 DOI: 10.1371/journal.pone.0191470 [Indexed for MEDLINE] Free PMC Article
EphA7 regulates claudin6 and pronephros development in Xenopus
Biochem Biophys Res Commun. 2018 Jan 8;495(2):1580-1587. doi: 10.1016/j.bbrc.2017.12.027. Epub 2017 Dec 6.
Sun J1, Wang X1, Shi Y2, Li J1, Li C1, Shi Z3, Chen Y3, Mao B4.
Abstract Eph/ephrin molecules are widely expressed during embryonic development, and function in a variety of developmental processes. Here we studied the roles of the Eph receptor EphA7 and its soluble form in Xenopus pronephros development. EphA7 is specifically expressed in pronephric tubules at tadpole stages and knockdown of EphA7 by a translation blocking morpholino led to defects in tubule cell differentiation and morphogenesis. A soluble form of EphA7 (sEphA7) was also identified. Interestingly, the membrane level of claudin6 (CLDN6), a tetraspan transmembrane tight junction protein, was dramatically reduced in the translation blocking morpholino injected embryos, but not when a splicing morpholino was used, which blocks only the full length EphA7. In cultured cells, EphA7 binds and phosphorylates CLDN6, and reduces its distribution at the cell surface. Our work suggests a role of EphA7 in the regulation of cell adhesion during pronephros development, whereas sEphA7 works as an antagonist. KEYWORDS: Claudin6; EphA7; Morphogenesis; Pronephros development; Soluble EphA7; Xenopus PMID: 29223398 DOI: 10.1016/j.bbrc.2017.12.027
The ectodomain of cadherin-11 binds to erbB2 and stimulates Akt phosphorylation to promote cranial neural crest cell migration
PLoS One. 2017 Nov 30;12(11):e0188963. doi: 10.1371/journal.pone.0188963. eCollection 2017.
Mathavan K1, Khedgikar V1, Bartolo V1, Alfandari D1.
During development, a multi-potent group of cells known as the cranial neural crest (CNC) migrate to form craniofacial structures. Proper migration of these cells requires proteolysis of cell adhesion molecules, such as cadherins. In Xenopus laevis, preventing extracellular cleavage of cadherin-11 impairs CNC migration. However, overexpression of the soluble cleavage product (EC1-3) is capable of rescuing this phenotype. The mechanism by which EC1-3 promotes CNC migration has not been investigated until now. Here we show that EC1-3 stimulates phosphorylation of Akt, a target of PI3K, in X.laevis CNC. Through immunoprecipitation experiments, we determined that EC1-3 interacts with all ErbB receptors, PDGFRα, and FGFR1. Of these receptors, only ErbB2 was able to produce an increase in Akt phosphorylation upon treatment with a recombinant EC1-3. This increase was abrogated by mubritinib, an inhibitor of ErbB2. We were able to recapitulate this decrease in Akt phosphorylation in vivo by knocking down ErbB2 in CNC cells. Knockdown of the receptor also significantly reduced CNC migration in vivo. We confirmed the importance of ErbB2 and ErbB receptor signaling in CNC migration using mubritinib and canertinib, respectively. Mubritinib and the PI3K inhibitor LY294002 significantly decreased cell migration while canertinib nearly prevented it altogether. These data show that ErbB2 and Akt are important for CNC migration and implicate other ErbB receptors and Akt-independent signaling pathways. Our findings provide the first example of a functional interaction between the extracellular domain of a type II classical cadherin and growth factor receptors. PMID: 29190819 PMCID: PMC5708760 DOI: 10.1371/journal.pone.0188963
N1-Src kinase is required for primary neurogenesis in Xenopus tropicalis
J Neurosci. 2017 Aug 1. pii: 3881-16. doi: 10.1523/JNEUROSCI.3881-16.2017. [Epub ahead of print]
Lewis PA1, Bradley IC1, Pizzey AR1, Isaacs HV2, Evans GJO2.
The presence of the neuronal-specific N1-Src splice variant of the C-Src tyrosine kinase is conserved through vertebrate evolution, suggesting an important role in complex nervous systems. Alternative splicing involving a N1-Src specific microexon leads to a five or six amino acid insertion into the SH3 domain of Src. A prevailing model suggests that N1-Src regulates neuronal differentiation via cytoskeletal dynamics in the growth cone. Here we have investigated the role of n1-src in the early development of the amphibian Xenopus tropicalis, and find that n1-src expression is regulated in embryogenesis, with highest levels detected during the phases of primary and secondary neurogenesis. In situ hybridisation analysis, using locked nucleic acid (LNA) oligo probes complementary to the n1-src microexon indicate that n1-src expression is highly enriched in the open neural plate during neurula stages and in the neural tissue of adult frogs. Given the n1-src expression pattern, we investigated a possible role for n1-src in neurogenesis. Using splice site-specific antisense morpholino oligos, we are able to inhibit n1-src splicing, whilst preserving c-src expression. Differentiation of neurons in the primary nervous system is reduced in n1-src knockdown embryos, accompanied by a severely impaired touch response in later development. These data reveal an essential role for n1-src in amphibian neural development and suggest that alternative splicing of C-Src in the developing vertebrate nervous system evolved to regulate neurogenesis.SIGNIFICANCE STATEMENTThe Src family of non-receptor tyrosine kinases act in signalling pathways that regulate cell migration, cell adhesion and proliferation. Srcs are also enriched in the brain where they play key roles in neuronal development and neurotransmission. Vertebrates have evolved a neuron-specific splice variant of C-Src, N1-Src, which differs from C-Src by just five or six amino acids. N1-Src is poorly understood and its high similarity to C-Src has made it difficult to delineate its function. Using antisense knockdown of the n1-src microexon, we have studied neuronal development in the Xenopus embryo in the absence of n1-src, whilst preserving c-src Loss of n1-src causes a striking absence of primary neurogenesis, implicating n1-src in the specification of neurons early in neural development. Copyright © 2017 Lewis et al.
PMID: 28765332 DOI: 10.1523/JNEUROSCI.3881-16.2017
Endocrine disruption by environmental gestagens in amphibians - A short review supported by new in vitro data using gonads of Xenopus laevis
Chemosphere. 2017 Aug;181:74-82. doi: 10.1016/j.chemosphere.2017.04.021. Epub 2017 Apr 5.
Ziková A1, Lorenz C2, Hoffmann F2, Kleiner W2, Lutz I2, Stöck M2, Kloas W3.
Endocrine disruption caused by various anthropogenic compounds is of persisting concern, especially for aquatic wildlife, because surface waters are the main sink of these so-called endocrine disruptors (ED). In the past, research focused on (anti)estrogenic, (anti)androgenic, and (anti)thyroidal substances, affecting primarily reproduction and development in vertebrates; however, other endocrine systems might be also targeted by ED. Environmental gestagens, including natural progestogens (e.g. progesterone (P4)) and synthetic progestins used for contraception, are supposed to affect vertebrate reproduction via progesterone receptors. In the present paper, we review the current knowledge about gestagenic effects in amphibians, focussing on reproduction and the thyroid system. In addition, we support the literature data with results of recent in vitro experiments, demonstrating direct impacts of the gestagens levonorgestrel (LNG) and P4 on sexually differentiated gonads of larval Xenopus laevis. The results showed a higher susceptibility of female over male gonads to gestagenic ED. Only in female gonads LNG, but not P4, had direct inhibitory effects on gene expression of steroidogenic acute regulatory protein and P450 side chain cleavage enzyme, whereas aromatase expression decreased in reaction to both gestagens. Surprisingly, beyond the expected ED effects of gestagens on reproductive physiology in amphibians, LNG drastically disrupted the thyroid system, which resembles direct effects on thyroid glands and pituitary along the pituitary-thyroid axis disturbing metamorphic development. In amphibians, environmental gestagens not only affect the reproductive system but at least LNG can impact also development by disruption of the thyroid system. Copyright © 2017 Elsevier Ltd. All rights reserved.
KEYWORDS: Amphibians; Endocrine disruption; Environmental gestagens; Gonads; Thyroid system PMID 28431277 DOI: 10.1016/j.chemosphere.2017.04.021
Xenopus Limb bud morphogenesis
Dev Dyn. 2016 Mar;245(3):233-43. doi: 10.1002/dvdy.24351. Epub 2015 Nov 3.
Keenan SR1, Beck CW1.
Xenopus laevis, the South African clawed frog, is a well-established model organism for the study of developmental biology and regeneration due to its many advantages for both classical and molecular studies of patterning and morphogenesis. While contemporary studies of limb development tend to focus on models developed from the study of chicken and mouse embryos, there are also many classical studies of limb development in frogs. These include both fate and specification maps, that, due to their age, are perhaps not as widely known or cited as they should be. This has led to some inevitable misinterpretations- for example, it is often said that Xenopus limb buds have no apical ectodermal ridge, a morphological signalling centre located at the distal dorsal/ventral epithelial boundary and known to regulate limb bud outgrowth. These studies are valuable both from an evolutionary perspective, because amphibians diverged early from the amniote lineage, and from a developmental perspective, as amphibian limbs are capable of regeneration. Here, we describe Xenopus limb morphogenesis with reference to both classical and molecular studies, to create a clearer picture of what we know, and what is still mysterious, about this process. © 2015 Wiley Periodicals, Inc.
KEYWORDS: amphibian; autopod; limb bud; mesoderm; morphogen; patterning; positional information; skeletal
PMID 26404044 DOI: 10.1002/dvdy.24351
Par6b regulates the dynamics of apicobasal polarity during development of the stratified Xenopus epidermis
PLoS One. 2013 Oct 18;8(10):e76854. doi: 10.1371/journal.pone.0076854. eCollection 2013.
Wang S1, Cha SW, Zorn AM, Wylie C.
During early vertebrate development, epithelial cells establish and maintain apicobasal polarity, failure of which can cause developmental defects or cancer metastasis. This process has been mostly studied in simple epithelia that have only one layer of cells, but is poorly understood in stratified epithelia. In this paper we address the role of the polarity protein Partitioning defective-6 homolog beta (Par6b) in the developing stratified epidermis of Xenopus laevis. At the blastula stage, animal blastomeres divide perpendicularly to the apicobasal axis to generate partially polarized superficial cells and non-polarized deep cells. Both cell populations modify their apicobasal polarity during the gastrula stage, before differentiating into the superficial and deep layers of epidermis. Early differentiation of the epidermis is normal in Par6b-depleted embryos; however, epidermal cells dissociate and detach from embryos at the tailbud stage. Par6b-depleted epidermal cells exhibit a significant reduction in basolaterally localized E-cadherin. Examination of the apical marker Crumbs homolog 3 (Crb3) and the basolateral marker Lethal giant larvae 2 (Lgl2) after Par6b depletion reveals that Par6b cell-autonomously regulates the dynamics of apicobasal polarity in both superficial and deep epidermal layers. Par6b is required to maintain the "basolateral" state in both epidermal layers, which explains the reduction of basolateral adhesion complexes and epidermal cells shedding. PMID 24204686
Par6b regulates the dynamics of apicobasal polarity during development of the stratified Xenopus epidermis
PLoS One. 2013 Oct 18;8(10):e76854. doi: 10.1371/journal.pone.0076854. eCollection 2013.
Wang S1, Cha SW, Zorn AM, Wylie C.
During early vertebrate development, epithelial cells establish and maintain apicobasal polarity, failure of which can cause developmental defects or cancer metastasis. This process has been mostly studied in simple epithelia that have only one layer of cells, but is poorly understood in stratified epithelia. In this paper we address the role of the polarity protein Partitioning defective-6 homolog beta (Par6b) in the developing stratified epidermis of Xenopus laevis. At the blastula stage, animal blastomeres divide perpendicularly to the apicobasal axis to generate partially polarized superficial cells and non-polarized deep cells. Both cell populations modify their apicobasal polarity during the gastrula stage, before differentiating into the superficial and deep layers of epidermis. Early differentiation of the epidermis is normal in Par6b-depleted embryos; however, epidermal cells dissociate and detach from embryos at the tailbud stage. Par6b-depleted epidermal cells exhibit a significant reduction in basolaterally localized E-cadherin. Examination of the apical marker Crumbs homolog 3 (Crb3) and the basolateral marker Lethal giant larvae 2 (Lgl2) after Par6b depletion reveals that Par6b cell-autonomously regulates the dynamics of apicobasal polarity in both superficial and deep epidermal layers. Par6b is required to maintain the "basolateral" state in both epidermal layers, which explains the reduction of basolateral adhesion complexes and epidermal cells shedding.
NumbL is essential for Xenopus primary neurogenesis
BMC Dev Biol. 2013 Oct 14;13:36. doi: 10.1186/1471-213X-13-36.
Nieber F1, Hedderich M, Jahn O, Pieler T, Henningfeld KA.
BACKGROUND: Members of the vertebrate Numb family of cell fate determinants serve multiple functions throughout early embryogenesis, including an essential role in the development of the nervous system. The Numb proteins interact with various partner proteins and correspondingly participate in multiple cellular activities, including inhibition of the Notch pathway. RESULTS: Here, we describe the expression characteristics of Numb and Numblike (NumbL) during Xenopus development and characterize the function of NumbL during primary neurogenesis. NumbL, in contrast to Numb, is expressed in the territories of primary neurogenesis and is positively regulated by the Neurogenin family of proneural transcription factors. Knockdown of NumbL afforded a complete loss of primary neurons and did not lead to an increase in Notch signaling in the open neural plate. Furthermore, we provide evidence that interaction of NumbL with the AP-2 complex is required for NumbL function during primary neurogenesis. CONCLUSION: We demonstrate an essential role of NumbL during Xenopus primary neurogenesis and provide evidence for a Notch-independent function of NumbL in this context. PMID 24125469
Wnt11b is involved in cilia-mediated symmetry breakage during Xenopus left-right development
PLoS One. 2013 Sep 13;8(9):e73646. doi: 10.1371/journal.pone.0073646. eCollection 2013.
Walentek P1, Schneider I, Schweickert A, Blum M.
Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP) give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis. Wnt signaling has previously been involved in two steps, Wnt/ß-catenin mediated induction of Foxj1, a regulator of motile cilia, and Wnt/planar cell polarity (PCP) dependent cilia polarization to the posterior pole of cells. We have studied Wnt11b in the context of laterality determination, as this ligand was reported to activate canonical and non-canonical Wnt signaling. Wnt11b was found to be expressed in the so-called superficial mesoderm (SM), from which the GRP derives. Surprisingly, Foxj1 was only marginally affected in loss-of-function experiments, indicating that another ligand acts in this early step of laterality specification. Wnt11b was required, however, for polarization of GRP cilia and GRP morphogenesis, in line with the known function of Wnt/PCP in cilia-driven leftward flow. In addition Xnr1 and Coco expression in the lateral-most GRP cells, which sense flow and generate the first asymmetric signal, was attenuated in morphants, involving Wnt signaling in yet another process related to symmetry breakage in Xenopus. PMID: 24058481
Variation in the schedules of somite and neural development in frogs
Proc Natl Acad Sci U S A. 2012 Nov 26. [Epub ahead of print]
Sáenz-Ponce N, Mitgutsch C, Del Pino EM. Source Escuela de Ciencias Biológicas, Pontificia Universidad Católica del Ecuador, Quito 17, Ecuador.
The timing of notochord, somite, and neural development was analyzed in the embryos of six different frog species, which have been divided into two groups, according to their developmental speed. Rapid developing species investigated were Xenopus laevis (Pipidae), Engystomops coloradorum, and Engystomops randi (Leiuperidae). The slow developers were Epipedobates machalilla and Epipedobates tricolor (Dendrobatidae) and Gastrotheca riobambae (Hemiphractidae). Blastopore closure, notochord formation, somite development, neural tube closure, and the formation of cranial neural crest cell-streams were detected by light and scanning electron microscopy and by immuno-histochemical detection of somite and neural crest marker proteins. The data were analyzed using event pairing to determine common developmental aspects and their relationship to life-history traits. In embryos of rapidly developing frogs, elongation of the notochord occurred earlier relative to the time point of blastopore closure in comparison with slowly developing species. The development of cranial neural crest cell-streams relative to somite formation is accelerated in rapidly developing frogs, and it is delayed in slowly developing frogs. The timing of neural tube closure seemed to be temporally uncoupled with somite formation. We propose that these changes are achieved through differential timing of developmental modules that begin with the elongation of the notochord during gastrulation in the rapidly developing species. The differences might be related to the necessity of developing a free-living tadpole quickly in rapid developers.
Toward an unbiased evolutionary platform for unraveling Xenopus developmental gene networks
Genesis. 2012 Mar;50(3):186-91. doi: 10.1002/dvg.20811. Epub 2012 Jan 5.
Beer R, Wagner F, Grishkevich V, Peshkin L, Yanai I. Source Department of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
The availability of both the Xenopus tropicalis genome and the soon to be released Xenopus laevis genome provides a solid foundation for Xenopus developmental biologists. The Xenopus community has presently amassed expression data for ∼2,300 genes in the form of published images collected in the Xenbase, the principal Xenopus research database. A few of these genes have been examined in both X. tropicalis and X. laevis and the cross-species comparison has been proven invaluable for studying gene function. A recently published work has yielded developmental expression profiles for the majority of Xenopus genes across fourteen developmental stages spanning the blastula, gastrula, neurula, and the tail-bud. While this data was originally queried for global evolutionary and developmental principles, here we demonstrate its general use for gene-level analyses. In particular, we present the accessibility of this dataset through Xenbase and describe biases in the characterized genes in terms of sequence and expression conservation across the two species. We further indicate the advantage of examining coexpression for gene function discovery relating to developmental processes conserved across species. We suggest that the integration of additional large-scale datasets--comprising diverse functional data--into Xenbase promises to provide a strong foundation for researchers in elucidating biological processes including the gene regulatory programs encoding development. Copyright © 2011 Wiley-Liss, Inc.
Identification and Characterization of the RLIP/RALBP1 Interacting Protein Xreps1 in Xenopus laevis Early Development
PLoS One. 2012;7(3):e33193. Epub 2012 Mar 8.
Boissel L, Fillatre J, Moreau J. Source Institut Jacques Monod, CNRS (UMR7592), Université Paris Diderot, Paris, France.
BACKGROUND: The FGF/Ras/Ral/RLIP pathway is required for the gastrulation process during the early development of vertebrates. The Ral Interacting Protein (RLIP also known as RalBP1) interacts with GTP-bound Ral proteins. RLIP/RalBP1 is a modular protein capable of participating in many cellular functions. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the role of RLIP in early development, a two-hybrid screening using a library of maternal cDNAs of the amphibian Xenopus laevis was performed. Xreps1 was isolated as a partner of RLIP/RalBP1 and its function was studied. The mutual interacting domains of Xreps1 and Xenopus RLIP (XRLIP) were identified. Xreps1 expressed in vivo, or synthesized in vitro, interacts with in vitro expressed XRLIP. Interestingly, targeting of Xreps1 or the Xreps1-binding domain of XRLIP (XRLIP(469-636)) to the plasma membrane through their fusion to the CAAX sequence induces a hyperpigmentation phenotype of the embryo. This hyperpigmented phenotype induced by XRLIP(469-636)-CAAX can be rescued by co-expression of a deletion mutant of Xreps1 restricted to the RLIP-binding domain (Xreps1(RLIP-BD)) but not by co-expression of a cDNA coding for a longer form of Xreps1. CONCLUSION/SIGNIFICANCE: We demonstrate here that RLIP/RalBP1, an effector of Ral involved in receptor-mediated endocytosis and in the regulation of actin dynamics during embryonic development, also interacts with Reps1. Although these two proteins are present early during embryonic development, they are active only at the end of gastrulation. Our results suggest that the interaction between RLIP and Reps1 is negatively controlled during the cleavage stage of development, which is characterized by rapid mitosis. Later in development, Reps1 is required for the normal function of the ectodermic cell, and its targeting into the plasma membrane affects the stability of the ectoderm.
Stage-specific histone modification profiles reveal global transitions in the Xenopus embryonic epigenome
PLoS One. 2011;6(7):e22548. Epub 2011 Jul 22.
Schneider TD, Arteaga-Salas JM, Mentele E, David R, Nicetto D, Imhof A, Rupp RA. Source Department of Molecular Biology, Adolf-Butenandt Institut, Ludwig-Maximilians-Universität München, Munich, Germany.
Vertebrate embryos are derived from a transitory pool of pluripotent cells. By the process of embryonic induction, these precursor cells are assigned to specific fates and differentiation programs. Histone post-translational modifications are thought to play a key role in the establishment and maintenance of stable gene expression patterns underlying these processes. While on gene level histone modifications are known to change during differentiation, very little is known about the quantitative fluctuations in bulk histone modifications during development. To investigate this issue we analysed histones isolated from four different developmental stages of Xenopus laevis by mass spectrometry. In toto, we quantified 59 modification states on core histones H3 and H4 from blastula to tadpole stages. During this developmental period, we observed in general an increase in the unmodified states, and a shift from histone modifications associated with transcriptional activity to transcriptionally repressive histone marks. We also compared these naturally occurring patterns with the histone modifications of murine ES cells, detecting large differences in the methylation patterns of histone H3 lysines 27 and 36 between pluripotent ES cells and pluripotent cells from Xenopus blastulae. By combining all detected modification transitions we could cluster their patterns according to their embryonic origin, defining specific histone modification profiles (HMPs) for each developmental stage. To our knowledge, this data set represents the first compendium of covalent histone modifications and their quantitative flux during normogenesis in a vertebrate model organism. The HMPs indicate a stepwise maturation of the embryonic epigenome, which may be causal to the progressing restriction of cellular potency during development.
Low frequency vibrations disrupt left-right patterning in the Xenopus embryo
PLoS One. 2011;6(8):e23306. Epub 2011 Aug 3.
Vandenberg LN, Pennarola BW, Levin M. Source Center for Regenerative and Developmental Biology, Tufts University, Medford, Massachusetts, United States of America.
The development of consistent left-right (LR) asymmetry across phyla is a fascinating question in biology. While many pharmacological and molecular approaches have been used to explore molecular mechanisms, it has proven difficult to exert precise temporal control over functional perturbations. Here, we took advantage of acoustical vibration to disrupt LR patterning in Xenopus embryos during tightly-circumscribed periods of development. Exposure to several low frequencies induced specific randomization of three internal organs (heterotaxia). Investigating one frequency (7 Hz), we found two discrete periods of sensitivity to vibration; during the first period, vibration affected the same LR pathway as nocodazole, while during the second period, vibration affected the integrity of the epithelial barrier; both are required for normal LR patterning. Our results indicate that low frequency vibrations disrupt two steps in the early LR pathway: the orientation of the LR axis with the other two axes, and the amplification/restriction of downstream LR signals to asymmetric organs.
Caldesmon regulates actin dynamics to influence cranial neural crest migration in Xenopus
Mol Biol Cell. 2011 Sep;22(18):3355-65. Epub 2011 Jul 27.
Nie S, Kee Y, Bronner-Fraser M. Source Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Caldesmon (CaD) is an important actin modulator that associates with actin filaments to regulate cell morphology and motility. Although extensively studied in cultured cells, there is little functional information regarding the role of CaD in migrating cells in vivo. Here we show that nonmuscle CaD is highly expressed in both premigratory and migrating cranial neural crest cells of Xenopus embryos. Depletion of CaD with antisense morpholino oligonucleotides causes cranial neural crest cells to migrate a significantly shorter distance, prevents their segregation into distinct migratory streams, and later results in severe defects in cartilage formation. Demonstrating specificity, these effects are rescued by adding back exogenous CaD. Interestingly, CaD proteins with mutations in the Ca(2+)-calmodulin-binding sites or ErK/Cdk1 phosphorylation sites fail to rescue the knockdown phenotypes, whereas mutation of the PAK phosphorylation site is able to rescue them. Analysis of neural crest explants reveals that CaD is required for the dynamic arrangements of actin and, thus, for cell shape changes and process formation. Taken together, these results suggest that the actin-modulating activity of CaD may underlie its critical function and is regulated by distinct signaling pathways during normal neural crest migration.
A comparative survey of the frequency and distribution of polymorphism in the genome of Xenopus tropicalis
PLoS One. 2011;6(8):e22392. Epub 2011 Aug 4.
Showell C, Carruthers S, Hall A, Pardo-Manuel de Villena F, Stemple D, Conlon FL. Source UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Naturally occurring DNA sequence variation within a species underlies evolutionary adaptation and can give rise to phenotypic changes that provide novel insight into biological questions. This variation exists in laboratory populations just as in wild populations and, in addition to being a source of useful alleles for genetic studies, can impact efforts to identify induced mutations in sequence-based genetic screens. The Western clawed frog Xenopus tropicalis (X. tropicalis) has been adopted as a model system for studying the genetic control of embryonic development and a variety of other areas of research. Its diploid genome has been extensively sequenced and efforts are underway to isolate mutants by phenotype- and genotype-based approaches. Here, we describe a study of genetic polymorphism in laboratory strains of X. tropicalis. Polymorphism was detected in the coding and non-coding regions of developmental genes distributed widely across the genome. Laboratory strains exhibit unexpectedly high frequencies of genetic polymorphism, with alleles carrying a variety of synonymous and non-synonymous codon substitutions and nucleotide insertions/deletions. Inter-strain comparisons of polymorphism uncover a high proportion of shared alleles between Nigerian and Ivory Coast strains, in spite of their distinct geographical origins. These observations will likely influence the design of future sequence-based mutation screens, particularly those using DNA mismatch-based detection methods which can be disrupted by the presence of naturally occurring sequence variants. The existence of a significant reservoir of alleles also suggests that existing laboratory stocks may be a useful source of novel alleles for mapping and functional studies. PMID 21829622
Expression of Wnt signaling components during Xenopus pronephros development
PLoS One. 2011;6(10):e26533. Epub 2011 Oct 19.
Zhang B, Tran U, Wessely O. Source Lerner Research Institute/Cleveland Clinic, Department of Cell Biology, Cleveland, Ohio, United States of America. Abstract BACKGROUND: The formation of the vertebrate kidney is tightly regulated and relies on multiple evolutionarily conserved inductive events. These are present in the complex metanephric kidney of higher vertebrates, but also in the more primitive pronephric kidney functional in the larval stages of amphibians and fish. Wnts have long been viewed as central in this process. Canonical β-Catenin-dependent Wnt signaling establishes kidney progenitors and non-canonical β-Catenin-independent Wnt signaling participate in the morphogenetic processes that form the highly sophisticated nephron structure. While some individual Wnt signaling components have been studied extensively in the kidney, the overall pathway has not yet been analyzed in depth. METHODOLOGY/PRINCIPAL FINDINGS: Here we report a detailed expression analysis of all Wnt ligands, receptors and several downstream Wnt effectors during pronephros development in Xenopus laevis using in situ hybridization. Out of 19 Wnt ligands, only three, Wnt4, Wnt9a and Wnt11, are specifically expressed in the pronephros. Others such as Wnt8a are present, but in a broader domain comprising adjacent tissues in addition to the kidney. The same paradigm is observed for the Wnt receptors and its downstream signaling components. Fzd1, Fzd4, Fzd6, Fzd7, Fzd8 as well as Celsr1 and Prickle1 show distinct expression domains in the pronephric kidney, whereas the non-traditional Wnt receptors, Ror2 and Ryk, as well as the majority of the effector molecules are rather ubiquitous. In addition to this spatial regulation, the timing of expression is also tightly regulated. In particular, non-canonical Wnt signaling seems to be restricted to later stages of pronephros development. CONCLUSION/SIGNIFICANCE: Together these data suggest a complex cross talk between canonical and non-canonical Wnt signaling is required to establish a functional pronephric kidney.
Different requirement for Wnt/β-catenin signaling in limb regeneration of larval and adult Xenopus
PLoS One. 2011;6(7):e21721. Epub 2011 Jul 26.
Yokoyama H, Maruoka T, Ochi H, Aruga A, Ohgo S, Ogino H, Tamura K. Source Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aoba-ku, Sendai, Japan. firstname.lastname@example.org
BACKGROUND: In limb regeneration of amphibians, the early steps leading to blastema formation are critical for the success of regeneration, and the initiation of regeneration in an adult limb requires the presence of nerves. Xenopus laevis tadpoles can completely regenerate an amputated limb at the early limb bud stage, and the metamorphosed young adult also regenerates a limb by a nerve-dependent process that results in a spike-like structure. Blockage of Wnt/β-catenin signaling inhibits the initiation of tadpole limb regeneration, but it remains unclear whether limb regeneration in young adults also requires Wnt/β-catenin signaling. METHODOLOGY/PRINCIPAL FINDINGS: We expressed heat-shock-inducible (hs) Dkk1, a Wnt antagonist, in transgenic Xenopus to block Wnt/β-catenin signaling during forelimb regeneration in young adults. hsDkk1 did not inhibit limb regeneration in any of the young adult frogs, though it suppressed Wnt-dependent expression of genes (fgf-8 and cyclin D1). When nerve supply to the limbs was partially removed, however, hsDkk1 expression blocked limb regeneration in young adult frogs. Conversely, activation of Wnt/β-catenin signaling by a GSK-3 inhibitor rescued failure of limb-spike regeneration in young adult frogs after total removal of nerve supply. CONCLUSIONS/SIGNIFICANCE: In contrast to its essential role in tadpole limb regeneration, our results suggest that Wnt/β-catenin signaling is not absolutely essential for limb regeneration in young adults. The different requirement for Wnt/β-catenin signaling in tadpoles and young adults appears to be due to the projection of nerve axons into the limb field. Our observations suggest that nerve-derived signals and Wnt/β-catenin signaling have redundant roles in the initiation of limb regeneration. Our results demonstrate for the first time the different mechanisms of limb regeneration initiation in limb buds (tadpoles) and developed limbs (young adults) with reference to nerve-derived signals and Wnt/β-catenin signaling.
Predator mediated selection and the impact of developmental stage on viability in wood frog tadpoles (Rana sylvatica)
BMC Evol Biol. 2011 Dec 7;11:353.
Calsbeek R, Kuchta S. Source Department of Biological Sciences, Dartmouth College, Hanover, NH 03755 USA. email@example.com.
ABSTRACT: BACKGROUND: Complex life histories require adaptation of a single organism for multiple ecological niches. Transitions between life stages, however, may expose individuals to an increased risk of mortality, as the process of metamorphosis typically includes developmental stages that function relatively poorly in both the pre- and post-metamorphic habitat. We studied predator-mediated selection on tadpoles of the wood frog, Rana sylvatica, to identify this hypothesized period of differential predation risk and estimate its ontogenetic onset. We reared tadpoles in replicated mesocosms in the presence of the larval odonate Anax junius, a known tadpole predator. RESULTS: The probability of tadpole survival increased with increasing age and size, but declined steeply at the point in development where hind limbs began to erupt from the body wall. Selection gradient analyses indicate that natural selection favored tadpoles with short, deep tail fins. Tadpoles resorb their tails as they progress toward metamorphosis, which may have led to the observed decrease in survivorship. Path models revealed that selection acted directly on tail morphology, rather than through its indirect influence on swimming performance. CONCLUSIONS: This is consistent with the hypothesis that tail morphology influences predation rates by reducing the probability a predator strikes the head or body.
Unfertilized frog eggs die by apoptosis following meiotic exit
BMC Cell Biol. 2011 Dec 23;12:56.
Tokmakov AA, Iguchi S, Iwasaki T, Fukami Y. Source Research Center for Environmental Genomics, Kobe University, Rokko dai 1-1, Nada, Kobe 657-8501, Japan. firstname.lastname@example.org.
Abstract ABSTRACT: BACKGROUND: A characteristic feature of frog reproduction is external fertilization accomplished outside the female's body. Mature fertilization-competent frog eggs are arrested at the meiotic metaphase II with high activity of the key meiotic regulators, maturation promoting factor (MPF) and cytostatic factor (CSF), awaiting fertilization. If the eggs are not fertilized within several hours of ovulation, they deteriorate and ultimately die by as yet unknown mechanism. RESULTS: Here, we report that the vast majority of naturally laid unfertilized eggs of the African clawed frog Xenopus laevis spontaneously exit metaphase arrest under various environmental conditions and degrade by a well-defined apoptotic process within 48 hours after ovulation. The main features of this process include cytochrome c release, caspase activation, ATP depletion, increase of ADP/ATP ratio, apoptotic nuclear morphology, progressive intracellular acidification, and egg swelling. Meiotic exit seems to be a prerequisite for execution of the apoptotic program, since (i) it precedes apoptosis, (ii) apoptotic events cannot be observed in the eggs maintaining high activity of MPF and CSF, and (iii) apoptosis in unfertilized frog eggs is accelerated upon early meiotic exit. The apoptotic features cannot be observed in the immature prophase-arrested oocytes, however, the maturation-inducing hormone progesterone renders oocytes susceptible to apoptosis. CONCLUSIONS: The study reveals that naturally laid intact frog eggs die by apoptosis if they are not fertilized. A maternal apoptotic program is evoked in frog oocytes upon maturation and executed after meiotic exit in unfertilized eggs. The meiotic exit is required for execution of the apoptotic program in eggs. The emerging anti-apoptotic role of meiotic metaphase arrest needs further investigation.
Remodeling of the metabolome during early frog development
PLoS One. 2011 Feb 4;6(2):e16881.
Vastag L, Jorgensen P, Peshkin L, Wei R, Rabinowitz JD, Kirschner MW.
Source Carl Icahn Laboratory, Department of Chemistry and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.
A rapid series of synchronous cell divisions initiates embryogenesis in many animal species, including the frog Xenopus laevis. After many of these cleavage cycles, the nuclear to cytoplasmic ratio increases sufficiently to somehow cause cell cycles to elongate and become asynchronous at the mid-blastula transition (MBT). We have discovered that an unanticipated remodeling of core metabolic pathways occurs during the cleavage cycles and the MBT in X. laevis, as evidenced by widespread changes in metabolite abundance. While many of the changes in metabolite abundance were consistently observed, it was also evident that different female frogs laid eggs with different levels of at least some metabolites. Metabolite tracing with heavy isotopes demonstrated that alanine is consumed to generate energy for the early embryo. dATP pools were found to decline during the MBT and we have confirmed that maternal pools of dNTPs are functionally exhausted at the onset of the MBT. Our results support an alternative hypothesis that the cell cycle lengthening at the MBT is triggered not by a limiting maternal protein, as is usually proposed, but by a decline in dNTP pools brought about by the exponentially increasing demands of DNA synthesis.
Dev Biol. 2011 Apr 15;352(2):317-28. Epub 2011 Feb 3.
Ploper D, Lee HX, De Robertis EM. Source Department of Biological Chemistry, Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095–1662, USA.
In Xenopus, dorsal-ventral (D-V) patterning can self-regulate after embryo bisection. This is mediated by an extracellular network of proteins secreted by the dorsal and ventral centers of the gastrula. Different proteins of similar activity can be secreted at these two poles, but under opposite transcriptional control. Here we show that Crescent, a dorsal protein, can compensate for the loss of Sizzled, a ventral protein. Crescent is a secreted Frizzled-Related Protein (sFRP) known to regulate Wnt8 and Wnt11 activity. We now find that Crescent also regulates the BMP pathway. Crescent expression was increased by the BMP antagonist Chordin and repressed by BMP4, while the opposite was true for Sizzled. Crescent knock-down increased the expression of BMP target genes, and synergized with Sizzled morpholinos. Thus, Crescent loss-of-function is compensated by increased expression of its ventral counterpart Sizzled. Crescent overexpression dorsalized whole embryos but not ventral half-embryos, indicating that Crescent requires a dorsal component to exert its anti-BMP activity. Crescent protein lost its dorsalizing activity in Chordin-depleted embryos. When co-injected, Crescent and Chordin proteins greatly synergized in the dorsalization of Xenopus embryos. The molecular mechanism of these phenotypes is explained by the ability of Crescent to inhibit Tolloid metalloproteinases, which normally degrade Chordin. Enzyme kinetic studies showed that Crescent was a competitive inhibitor of Tolloid activity, which bound to Tolloid/BMP1 with a K(D) of 11 nM. In sum, Crescent is a new component of the D-V pathway, which functions as the dorsal counterpart of Sizzled, through the regulation of chordinases of the Tolloid family.
Copyright © 2011 Elsevier Inc. All rights reserved.
PMID: 21295563 http://www.ncbi.nlm.nih.gov/pubmed/21295563
<pubmed>19896938</pubmed>"During the climax of amphibian metamorphosis many tadpole organs remodel. The different remodeling strategies are controlled by thyroid hormone (TH). The liver, skin, and tail fibroblasts shut off tadpole genes and activate frog genes in the same cell without DNA replication. We refer to this as "gene switching". In contrast, the exocrine pancreas and the intestinal epithelium dedifferentiate to a progenitor state and then redifferentiate to the adult cell type."
Organizing early for left-right asymmetry
Organizing early for left-right asymmetry Development 2010 137:e702
"Although the overall vertebrate body plan is bilaterally symmetrical, internal organs show consistent left-right (LR) asymmetry. One model proposes that the motion of nodal cilia during gastrulation sets LR asymmetry. However, on p. 1095, Laura Vandenberg and Michael Levin show that in Xenopus embryos the crucial LR asymmetry events occur shortly after fertilization, well before ciliogenesis. The researchers ablate the primary dorsal organizer by UV irradiation, induce a new organizer either early (before cleavage) or late (after the 32-cell stage), and then examine the position of the heart, stomach and gall bladder. The LR axis is usually properly oriented when the new organizer is induced early, they report, but not when it is induced late. Intriguingly, late-induced organizers can correctly orient asymmetry if instructed by a conjoined twin arising from an organizer that was present during the first cleavages. Together, these results suggest that very early symmetry-breaking events, rather than events happening at the node during gastrulation, are of prime importance in establishing LR asymmetry in Xenopus embryos."
Consistent left-right asymmetry cannot be established by late organizers in Xenopus unless the late organizer is a conjoined twin
Vandenberg LN, Levin M. Development. 2010 Apr;137(7):1095-105. PMID: 20215347
- "How embryos consistently orient asymmetries of the left-right (LR) axis is an intriguing question, as no macroscopic environmental cues reliably distinguish left from right. Especially unclear are the events coordinating LR patterning with the establishment of the dorsoventral (DV) axes and midline determination in early embryos. In frog embryos, consistent physiological and molecular asymmetries manifest by the second cell cleavage; however, models based on extracellular fluid flow at the node predict correct de novo asymmetry orientation during neurulation. We addressed these issues in Xenopus embryos by manipulating the timing and location of dorsal organizer induction: the primary dorsal organizer was ablated by UV irradiation, and a new organizer was induced at various locations, either early, by mechanical rotation, or late, by injection of lithium chloride (at 32 cells) or of the transcription factor XSiamois (which functions after mid-blastula transition). These embryos were then analyzed for the position of three asymmetric organs. Whereas organizers rescued before cleavage properly oriented the LR axis 90% of the time, organizers induced in any position at any time after the 32-cell stage exhibited randomized laterality. Late organizers were unable to correctly orient the LR axis even when placed back in their endogenous location. Strikingly, conjoined twins produced by late induction of ectopic organizers did have normal asymmetry. These data reveal that although correct LR orientation must occur no later than early cleavage stages in singleton embryos, a novel instructive influence from an early organizer can impose normal asymmetry upon late organizers in the same cell field."
<pubmed>19334283</pubmed>"This review focuses specifically on Xenopus pancreas development, and covers events from the end of gastrulation, when regional specification of the endoderm is occurring, right through metamorphosis, when the mature pancreas is fully formed."
Translocation of repetitive RNA sequences with the germ plasm in Xenopus oocytes
Science. 1993 Dec 10;262(5140):1712-4.
Kloc M, Spohr G, Etkin LD. Source Department of Molecular Genetics, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Xlsirts are a family of interspersed repeat RNAs from Xenopus laevis that contain from 3 to 13 repeat units (each 79 to 81 nucleotides long) flanked by unique sequences. They are homologous to the mammalian Xist gene that is involved in X chromosome inactivation. Xlsirt RNA appears first in the mitochondrial cloud (Balbiani body) in stage 2 oocytes and is then translocated as island-like structures to the vegetal cortex at early stage 3 coincident with the localization of the germ plasm. Exogenous Xlsirt RNA injected into oocytes translocates to the location of the endogenous RNA at that particular stage. The Xlsirt RNA repeat sequences are required for translocation and can cause the translocation of heterologous unique RNAs to the vegetal cortex.
- Neural Induction in Xenopus: Requirement for Ectodermal and Endomesodermal Signals via Chordin, Noggin, β-Catenin, and Cerberus
- Controlling the Timing of Gene Expression during Organ Development
- Organizing the Vertebrate Embryo—A Balance of Induction and Competence
- Genetic Screens for Mutations Affecting Development of Xenopus tropicalis Tadahiro Goda, Anita Abu-Daya, Samantha Carruthers, Matthew D Clark, Derek L Stemple, and Lyle B Zimmerman PLoS Genet. 2006 June; 2(6): e91. Prepublished online 2006 April 28. Published online 2006 June 9. doi: 10.1371/journal.pgen.0020091. PMCID: PMC1475704
Frog Mitochondrial Genome
The complete nucleotide sequence of the Xenopus laevis mitochondrial genome. "The complete sequence of the 17,553-nucleotide Xenopus laevis mitochondrial genome has been determined. A comparison of this amphibian mitochondrial genomic sequence with those of the mammalian mitochondrial genomes reveals a similar gene order and compact genomic organization."
Xenopus laevis mitochondrial DNA, complete genome - 17553 bp GenBank report
- Eukaryotae; mitochondrial eukaryotes; Metazoa; Chordata;Vertebrata; Amphibia; Batrachia; Anura; Mesobatrachia; Pipoidea;Pipidae; Xenopodinae; Xenopus
Taxonomy Id: 8404 Preferred common name: northern leopard frog Rank: species
Genetic code: Translation table 1 (Standard) Mitochondrial genetic code: Translation table 2 Lineage( abbreviated ):
- Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Amphibia; Batrachia; Anura; Neobatrachia; Ranoidea; Ranidae; Raninae; Rana
External WWW Links
Note the dynamic developmental nature of the Internet means that some links may not always work (search using the link term).
- Xenbase A database of information pertaining to the cell and developmental biology of the frog, Xenopus
- Xenopus Laboratory List A database of Labs studying Xenopus
- Xenopus Microarrays
- Xenopus Cell Biology
- The Xenopus Molecular Marker Resource
- An electronic library of information on embryonic development of the frog, Xenopus laevis.
- Excellent site designed and Managed by Peter D. Vize, UT Austin.
- Index page for all Markers
- It also contains a collection of wholemount staining patterns
- Molecular Markers of Development
- cement gland; XA, XAG, XCG
- early mesoderm; BMP2, BMP4, Chordin, goosecoid, Mix,[Marker_pages/organizer/noggin.html noggin], Xbra, Xnr3, Xwnt-8, XVent1 and XVent2
- endothelial; Xl-fli
- germ cells; Xpat
- heart; cardiac troponin I , XNKX-2.5, XTin1 (XNKX-2.3)
- lateral line; tor70, [Marker_pages/CNS/2G9.html 2G9]
- muscle; 5A3, 12/101, cardiac actin, XMyf-5, XMyoD
- neural crest; Slug, XTwist , xAP2
- notochord: Xnot, tor70
- pronephros; [Marker_pages/pronephros/3G8.html 3G8 ], Wilms' tumor (xWT1), Xlim-1, Xwnt-4
- pronephric duct; 4A6
- Frogs of Greater Brisbane Region (Australia)
- An electronic library of information on embryonic development of the frog, Xenopus laevis.
- DNA SequenceXenopus laevis mitochondrial DNA, complete genome- 17553 bp
- gi|343717|gb|M10217.1|XELMTCG  View GenBank report
- The complete nucleotide sequence of the Xenopus laevis mitochondrial genome. Roe,B.A., Ma,D.P., Wilson,R.K. and Wong,J.F. J. Biol. Chem. 260 (17), 9759-9774 (1985)
- Abstract: The complete sequence of the 17,553-nucleotide Xenopus laevis mitochondrial genome has been determined. A comparison of this amphibian mitochondrial genomic sequence with those of the mammalian mitochondrial genomes reveals a similar gene order and compact genomic organization.
- Developmental Biology- Laurie Iten's Serially Sectioned Frog and Chick Embryos
- Developmental Biology- Jeff Hardin's Amphibian Embryology Tutorial
- NIH- Organisms for biomedical research
Requires internet connection.
Developmental Biology (6th ed) Gilbert: Frog Life Cycle
Molecular Cell Biology (4th ed.)Lodish Figure 23-5. Early embryogenesis of the frog Xenopus laevis
- Organisation of Xenopus oocyte and egg cortices. Chang P, Perez-Mongiovi D, Houliston E Microsc Res Tech 1999 Mar 15;44(6):415-29
- Abstract: The division of the Xenopus oocyte cortex into structurally and functionally distinct "animal" and "vegetal" regions during oogenesis provides the basis of the organisation of the early embryo. The vegetal region of the cortex accummulates specific maternal mRNAs that specify the development of the endoderm and mesoderm, as well as functionally-defined "determinants" of dorso-anterior development, and recognisable "germ plasm" determinants that segregate into primary germ cells. These localised elements on the vegetal cortex underlie both the primary animal-vegetal polarity of the egg and the organisation of the developing embryo. The animal cortex meanwhile becomes specialised for the events associated with fertilisation: sperm entry, calcium release into the cytoplasm, cortical granule exocytosis, and polarised cortical contraction. Cortical and subcortical reorganisations associated with meiotic maturation, fertilisation, cortical rotation, and the first mitotic cleavage divisions redistribute the vegetal cortical determinants, contributing to the specification of dorso-anterior axis and segregation of the germ line. In this article we consider what is known about the changing organisation of the oocyte and egg cortex in relation to the mechanisms of determinant localisation, anchorage, and redistribution, and show novel ultrastructural views of cortices isolated at different stages and processed by the rapid-freeze deep-etch method. Cortical organisation involves interactions between the different cytoskeletal filament systems and internal membranes. Associated proteins and cytoplasmic signals probably modulate these interactions in stage-specific ways, leaving much to be understood.
- Translocation of a localized maternal mRNA to the vegetal pole of Xenopus oocytes. Melton DA Nature 1987 Jul 2-8;328(6125):80-2
- A key paper in establishing localization of maternal mRNAs as regulators of developmental pattern formation. This localization of mRNAs has also been found for many different drosophila (fly) mRNAs with many different patterns.
- Abstract: A prominent hypothesis in embryology is that localized maternal factors are important in specifying cell fate. There are, however, only a few examples of maternal molecules that have been shown to be localized and very little is known about how such factors are physically localized within an egg (for review see ref. 1). Previously, cDNA clones were obtained for a class of localized maternal mRNAs from Xenopus laevis. These mRNAs are unusual in that they are concentrated at either the animal or vegetal pole of unfertilized eggs. In the present study the synthesis and intracellular distribution of one of them, Vg1, has been examined during oogenesis. The results show that Vg1 mRNA is localized as a crescent at the vegetal pole of mature oocytes. Surprisingly, this mRNA is uniformly distributed in the cytoplasm of immature oocytes. These findings suggest that a single cell, the frog oocyte, has some mechanism for translocating specific RNAs like Vg1. The process that moves Vg1 mRNA is evidently a cytoplasmic localization machinery which is not directly coupled to the synthesis of Vg1 RNA.
- A two-step model for the localization of maternal mRNA in Xenopus oocytes: involvement of microtubules and microfilaments in the translocation and anchoring of Vg1 mRNA. Yisraeli JK, Sokol S, Melton DA Development 1990 Feb;108(2):289-98.
- Abstract: In an effort to understand how polarity is established in Xenopus oocytes, we have analyzed the process of localization of the maternal mRNA, Vg1. In fully grown oocytes, Vg1 mRNA is tightly localized at the vegetal cortex. Biochemical fractionation shows that the mRNA is preferentially associated with a detergent-insoluble subcellular fraction. The use of cytoskeletal inhibitors suggests that (1) microtubules are involved in the translocation of the message to the vegetal hemisphere and (2) microfilaments are important for the anchoring of the message at the cortex. Furthermore, immunohistochemistry reveals that a cytoplasmic microtubule array exists during translocation. These results suggest a role for the cytoskeleton in localizing information in the oocyte.
- RNA sorting in Xenopus oocytes and embryos. Mowry KL, Cote CA FASEB J 1999 Mar;13(3):435-45
- mRNA localisation during development. Micklem DR Dev Biol 1995 Dec;172(2):377-95.
- Thyroid hormone-dependent metamorphosis in a direct developing frog. Callery, EM and Elinson RP, Proc. Natl. Acad. Sci. USA, Vol. 97, Issue 6, 2615-2620, March 14, 2000
- The direct developing anuran, Eleutherodactylus coqui, lacks a tadpole, hatching as a tiny frog. We investigated the role of the metamorphic trigger, thyroid hormone (TH), in this unusual ontogeny. Expression patterns of the thyroid hormone receptors, TR and TR, were similar to those of indirect developers. TR mRNA levels increased dramatically around the time of thyroid maturation, when remodeling events reminiscent of metamorphosis occur. Treatment with the goitrogen methimazole inhibited this remodeling, which was reinitiated on cotreatment with TH. Despite their radically altered ontogeny, direct developers still undergo a TH-dependent metamorphosis, which occurs before hatching. We propose a new model for the evolution of anuran direct development.
On the Structure and Development of the Skull of the Common Frog (Rana temporaria, L.) (January 1, 1871) http://archive.org/details/philtrans05966609
On the Development of the Teeth of the Newt, the Frog, and Certain Lizards. (January 1, 1874) http://archive.org/details/philtrans03024546
The frog; its reproduction and development (1951) http://archive.org/details/frogitsreproduct00rugh
Some Experiments on the Development and Regeneration of the Eye and the Nasal Organ in Frog Embryos (February 1, 1908)