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1.
Nat Rev Mol Cell Biol ; 21(6): 341-352, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32300252

RESUMEN

Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly. This growing interest warrants the need for a consensus among researchers when referring to and undertaking research on EMT. This Consensus Statement, mediated by 'the EMT International Association' (TEMTIA), is the outcome of a 2-year-long discussion among EMT researchers and aims to both clarify the nomenclature and provide definitions and guidelines for EMT research in future publications. We trust that these guidelines will help to reduce misunderstanding and misinterpretation of research data generated in various experimental models and to promote cross-disciplinary collaboration to identify and address key open questions in this research field. While recognizing the importance of maintaining diversity in experimental approaches and conceptual frameworks, we emphasize that lasting contributions of EMT research to increasing our understanding of developmental processes and combatting cancer and other diseases depend on the adoption of a unified terminology to describe EMT.


Asunto(s)
Investigación Biomédica/normas , Transición Epitelial-Mesenquimal , Animales , Movimiento Celular , Plasticidad de la Célula , Consenso , Biología Evolutiva/normas , Humanos , Neoplasias/patología , Terminología como Asunto
3.
PLoS Comput Biol ; 20(2): e1011270, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38324613

RESUMEN

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.


Asunto(s)
Inteligencia Artificial , Programas Informáticos , Humanos , Nube Computacional , Edición
4.
Mol Biol Evol ; 40(9)2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37695804

RESUMEN

Uric acid is the main means of nitrogen excretion in uricotelic vertebrates (birds and reptiles) and the end product of purine catabolism in humans and a few other mammals. While uricase is inactivated in mammals unable to degrade urate, the presence of orthologous genes without inactivating mutations in avian and reptilian genomes is unexplained. Here we show that the Gallus gallus gene we name cysteine-rich urate oxidase (CRUOX) encodes a functional protein representing a unique case of cysteine enrichment in the evolution of vertebrate orthologous genes. CRUOX retains the ability to catalyze urate oxidation to hydrogen peroxide and 5-hydroxyisourate (HIU), albeit with a 100-fold reduced efficiency. However, differently from all uricases hitherto characterized, it can also facilitate urate regeneration from HIU, a catalytic property that we propose depends on its enrichment in cysteine residues. X-ray structural analysis highlights differences in the active site compared to known orthologs and suggests a mechanism for cysteine-mediated self-aggregation under H2O2-oxidative conditions. Cysteine enrichment was concurrent with the transition to uricotelism and a shift in gene expression from the liver to the skin where CRUOX is co-expressed with ß-keratins. Therefore, the loss of urate degradation in amniotes has followed opposite evolutionary trajectories: while uricase has been eliminated by pseudogenization in some mammals, it has been repurposed as a redox-sensitive enzyme in the reptilian skin.


Asunto(s)
Cisteína , Reptiles , Piel , Urato Oxidasa , Animales , Cisteína/genética , Peróxido de Hidrógeno , Piel/enzimología , Urato Oxidasa/genética , Urato Oxidasa/metabolismo , Ácido Úrico , Pollos/genética , Reptiles/genética , Reptiles/metabolismo
5.
PLoS Biol ; 14(1): e1002342, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26752627

RESUMEN

The iPlant Collaborative provides life science research communities access to comprehensive, scalable, and cohesive computational infrastructure for data management; identity management; collaboration tools; and cloud, high-performance, high-throughput computing. iPlant provides training, learning material, and best practice resources to help all researchers make the best use of their data, expand their computational skill set, and effectively manage their data and computation when working as distributed teams. iPlant's platform permits researchers to easily deposit and share their data and deploy new computational tools and analysis workflows, allowing the broader community to easily use and reuse those data and computational analyses.


Asunto(s)
Biología Computacional/organización & administración , Internet , Programas Informáticos
6.
J Hered ; 110(2): 194-210, 2019 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-30597046

RESUMEN

Next-generation sequencing (NGS) and expression technologies were utilized to investigate the genes and sequence elements in a 586 kb region of chicken chromosome 1 associated with the autosomal recessive diplopodia-1 (dp-1) mutation. This mutation shows a syndromic phenotype similar to known human developmental abnormalities (e.g., cleft palate, polydactyly, omphalocele [exposed viscera]). Toward our goal to ascertain the variant responsible, the entire 586 kb region was sequenced following utilization of a specifically designed capture array and to confirm/validate fine-mapping results. Bioinformatic analyses identified a total of 6142 sequence variants, which included SNPs, indels, and gaps. Of these, 778 SNPs, 146 micro-indels, and 581 gaps were unique to the UCD-Dp-1.003 inbred congenic line; those found within exons and splice sites were studied for contribution to the mutant phenotype. Upon further validation with additional mutant samples, a smaller subset (of variants [51]) remains linked to the mutation. Additionally, utilization of specific samples in the NGS technology was advantageous in that fine-mapping methodologies eliminated an additional 326 kb of sequence information on chromosome 1. Predicted and confirmed protein-coding genes within the smaller 260 kb region were assessed for their developmental expression patterns over several stages of early embryogenesis in regions/tissues of interest (e.g., digits, craniofacial region). Based on these results and known function in other vertebrates, 2 genes within 5 kb of each other, MRE11 and GPR83, are proposed as high-priority candidates for the dp-1 mutation.


Asunto(s)
Pollos/genética , Anomalías Craneofaciales/genética , Deformidades Congénitas de las Extremidades/genética , Proteína Homóloga de MRE11/genética , Receptores Acoplados a Proteínas G/genética , Animales , Mapeo Cromosómico , Anomalías Craneofaciales/diagnóstico , Análisis Mutacional de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Deformidades Congénitas de las Extremidades/diagnóstico , Mutación , Síndrome
8.
Nucleic Acids Res ; 42(Database issue): D933-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24150938

RESUMEN

GEISHA (Gallus Expression In Situ Hybridization Analysis; http://geisha.arizona.edu) is an in situ hybridization gene expression and genomic resource for the chicken embryo. This update describes modifications that enhance its utility to users. During the past 5 years, GEISHA has undertaken a significant restructuring to more closely conform to the data organization and formatting of Model Organism Databases in other species. This has involved migrating from an entry-centric format to one that is gene-centered. Database restructuring has enabled the inclusion of data pertaining to chicken genes and proteins and their orthologs in other species. This new information is presented through an updated user interface. In situ hybridization data in mouse, frog, zebrafish and fruitfly are integrated with chicken genomic and expression information. A resource has also been developed that integrates the GEISHA interface information with the Online Mendelian Inheritance in Man human disease gene database. Finally, the Chicken Gene Nomenclature Committee database and the GEISHA database have been integrated so that they draw from the same data resources.


Asunto(s)
Embrión de Pollo/metabolismo , Pollos/genética , Bases de Datos Genéticas , Expresión Génica , Animales , Genómica , Hibridación in Situ , Internet , Ratones , Modelos Animales , ARN Mensajero/análisis
9.
Dev Dyn ; 243(3): 497-508, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24166734

RESUMEN

BACKGROUND: Transforming growth factor-beta (TGFß) signaling regulates a myriad of biological processes during embryogenesis, in the adult, and during the manifestation of disease. TGFß signaling is propagated through one of three TGFß ligands interacting with Type I and Type II receptors, and Type III co-receptors. Although TGFß signaling is regulated partly by the combinatorial expression patterns of TGFß receptors and ligands, a comprehensive gene expression analysis has not been published. RESULTS: Here we report the embryonic mRNA expression patterns in chicken embryos of the canonical TGFß ligands (TGFB1, TGFB2, and TGFB3) and receptors (TGFBR1, TGFBR2, TGFBR3), plus the Activin A receptor, type 1 (ACVR1) and co receptor Endoglin (ENG) that also transduce TGFß signaling. CONCLUSIONS: TGFB ligands and receptors show dynamic and frequently overlapping expression patterns in numerous embryonic cell layers and structures. Integrating expression information identifies combinations of ligands and receptors that are involved in specific developmental processes including somitogenesis, cardiogenesis and vasculogenesis.


Asunto(s)
Proteínas Aviares/biosíntesis , Desarrollo Embrionario/fisiología , Regulación del Desarrollo de la Expresión Génica/fisiología , Receptores de Factores de Crecimiento Transformadores beta/biosíntesis , Factor de Crecimiento Transformador beta/biosíntesis , Animales , Antígenos CD/biosíntesis , Antígenos CD/genética , Proteínas Aviares/genética , Embrión de Pollo , Receptores de Factores de Crecimiento Transformadores beta/genética , Factor de Crecimiento Transformador beta/genética
10.
Proc Natl Acad Sci U S A ; 108(48): 19240-5, 2011 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-22084120

RESUMEN

Neural crest stem cells can be isolated from differentiated cultures of human pluripotent stem cells, but the process is inefficient and requires cell sorting to obtain a highly enriched population. No specific method for directed differentiation of human pluripotent cells toward neural crest stem cells has yet been reported. This severely restricts the utility of these cells as a model for disease and development and for more applied purposes such as cell therapy and tissue engineering. In this report, we use small-molecule compounds in a single-step method for the efficient generation of self-renewing neural crest-like stem cells in chemically defined media. This approach is accomplished directly from human pluripotent cells without the need for coculture on feeder layers or cell sorting to obtain a highly enriched population. Critical to this approach is the activation of canonical Wnt signaling and concurrent suppression of the Activin A/Nodal pathway. Over 12-14 d, pluripotent cells are efficiently specified along the neuroectoderm lineage toward p75(+) Hnk1(+) Ap2(+) neural crest-like cells with little or no contamination by Pax6(+) neural progenitors. This cell population can be clonally amplified and maintained for >25 passages (>100 d) while retaining the capacity to differentiate into peripheral neurons, smooth muscle cells, and mesenchymal precursor cells. Neural crest-like stem cell-derived mesenchymal precursors have the capacity for differentiation into osteocytes, chondrocytes, and adipocytes. In sum, we have developed methods for the efficient generation of self-renewing neural crest stem cells that greatly enhance their potential utility in disease modeling and regenerative medicine.


Asunto(s)
Diferenciación Celular/fisiología , Cresta Neural/citología , Células Madre Pluripotentes/citología , Transducción de Señal/fisiología , Proteínas Smad/metabolismo , Ingeniería de Tejidos/métodos , Proteínas Wnt/metabolismo , Western Blotting , Técnicas de Cultivo de Célula , Humanos , Microscopía Fluorescente , Reacción en Cadena en Tiempo Real de la Polimerasa
11.
J Biol Chem ; 287(46): 38505-14, 2012 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-22995917

RESUMEN

FGF signaling plays a pivotal role in regulating cell movements and lineage induction during gastrulation. Here we identify 44 microRNAs that are expressed in the primitive streak region of gastrula stage chicken embryos. We show that the primary effect of FGF signaling on microRNA abundance is to negatively regulate the levels of miR-let-7b, -9, -19b, -107, -130b, and -218. LIN28B inhibits microRNA processing and is positively regulated by FGF signaling. Gain- and loss-of-function experiments show that LIN28B negatively regulates the expression of miR-19b, -130b, and let-7b, whereas negative modulation of miR-9, -107, and -218 appears to be independent of LIN28B function. Predicted mRNA targets of the FGF-regulated microRNAs are over-represented in serine/threonine and tyrosine kinase receptors, including ACVR1, ACVR2B, PDGFRA, TGFBR1, and TGFBR3. Luciferase assays show that these and other candidates are targeted by FGF-regulated microRNAs. PDGFRA, a receptor whose activity is required for cell migration through the primitive streak, is a target of miR-130b and -218 in vivo. These results identify a novel mechanism by which FGF signaling regulates gene expression by negatively modulating microRNA abundance through both LIN28B-dependent and LIN28B-independent pathways.


Asunto(s)
Factores de Crecimiento de Fibroblastos/metabolismo , Proteínas Represoras/metabolismo , Animales , Tipificación del Cuerpo/genética , Movimiento Celular , Embrión de Pollo , Proteínas de Unión al ADN/metabolismo , Gástrula/metabolismo , Gastrulación , Regulación del Desarrollo de la Expresión Génica , Células HeLa , Humanos , Hibridación in Situ , MicroARNs/metabolismo , Conformación de Ácido Nucleico , Proteínas Tirosina Quinasas/metabolismo , Transducción de Señal
12.
Dev Dyn ; 246(12): 969, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29144604
13.
J Cell Sci ; 123(Pt 18): 3136-45, 2010 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-20736303

RESUMEN

Regulation of actin filament assembly is essential for efficient contractile activity in striated muscle. Leiomodin is an actin-binding protein and homolog of the pointed-end capping protein, tropomodulin. These proteins are structurally similar, sharing a common domain organization that includes two actin-binding sites. Leiomodin also contains a unique C-terminal extension that has a third actin-binding WH2 domain. Recently, the striated-muscle-specific isoform of leiomodin (Lmod2) was reported to be an actin nucleator in cardiomyocytes. Here, we have identified a function of Lmod2 in the regulation of thin filament lengths. We show that Lmod2 localizes to the pointed ends of thin filaments, where it competes for binding with tropomodulin-1 (Tmod1). Overexpression of Lmod2 results in loss of Tmod1 assembly and elongation of the thin filaments from their pointed ends. The Lmod2 WH2 domain is required for lengthening because its removal results in a molecule that caps the pointed ends similarly to Tmod1. Furthermore, Lmod2 transcripts are first detected in the heart after it has begun to beat, suggesting that the primary function of Lmod2 is to maintain thin filament lengths in the mature heart. Thus, Lmod2 antagonizes the function of Tmod1, and together, these molecules might fine-tune thin filament lengths.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Proteínas de Microfilamentos/metabolismo , Miocardio/metabolismo , Tropomiosina/antagonistas & inhibidores , Tropomiosina/metabolismo , Citoesqueleto de Actina/química , Animales , Células Cultivadas , Embrión de Pollo , Proteínas de Microfilamentos/química , Proteínas de Microfilamentos/genética , Células Musculares/metabolismo , Miocardio/química , Unión Proteica , Estructura Terciaria de Proteína , Transporte de Proteínas , Tropomiosina/química , Tropomiosina/genética
14.
RNA ; 16(3): 632-7, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-20086052

RESUMEN

In situ hybridization is widely used to visualize transcribed sequences in embryos, tissues, and cells. For whole mount detection of mRNAs in embryos, hybridization with an antisense RNA probe is followed by visual or fluorescence detection of target mRNAs. A limitation of this approach is that a cDNA template of the target RNA must be obtained in order to generate the antisense RNA probe. Here we investigate the use of short (12-24 nucleotides) locked nucleic acid (LNA) containing DNA probes for whole mount in situ hybridization detection of mRNAs. Following extensive protocol optimization, we show that LNA probes can be used to localize several mRNAs of varying abundances in chicken embryos. LNA probes also detected alternatively spliced exons that are processed in a tissue specific manner. The use of LNA probes for whole mount in situ detection of mRNAs will enable in silico design and chemical synthesis and will expand the general use of in situ hybridization for studies of transcriptional regulation and alternative splicing.


Asunto(s)
Embrión de Pollo/química , Técnicas Genéticas , Hibridación in Situ/métodos , Oligonucleótidos/química , ARN Mensajero/análisis , Empalme Alternativo , Animales , Conectina , Proteínas Musculares/genética , Proteínas Musculares/metabolismo
16.
BMC Evol Biol ; 11: 302, 2011 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-21999483

RESUMEN

BACKGROUND: The forkhead transcription factor gene E1 (FOXE1) plays an important role in regulation of thyroid development, palate formation and hair morphogenesis in mammals. However, avian FOXE1 genes have not been characterized and as such, codon evolution of FOXE1 orthologs in a broader evolutionary context of mammals and birds is not known. RESULTS: In this study we identified the avian FOXE1 gene in chicken, turkey and zebra finch, all of which consist of a single exon. Chicken and zebra finch FOXE1 are uniquely located on the sex-determining Z chromosome. In situ hybridization shows that chicken FOXE1 is specifically expressed in the developing thyroid. Its expression is initiated at the placode stage and is maintained during the stages of vesicle formation and follicle primordia. Based on this expression pattern, we propose that avian FOXE1 may be involved in regulating the evagination and morphogenesis of thyroid. Chicken FOXE1 is also expressed in growing feathers. Sequence analysis identified two microdeletions in the avian FOXE1 genes, corresponding to the loss of a transferable repression domain and an engrailed homology motif 1 (Eh1) C-terminal to the forkhead domain. The avian FOXE1 proteins exhibit a significant sequence divergence of the C-terminus compared to those of amphibian and mammalian FOXE1. The codon evolution analysis (dN/dS) of FOXE1 shows a significantly increased dN/dS ratio in the avian lineages, consistent with either a relaxed purifying selection or positive selection on a few residues in avian FOXE1 evolution. Further site specific analysis indicates that while relaxed purifying selection is likely to be a predominant cause of accelerated evolution at the 3'-region of avian FOXE1, a few residues might have evolved under positive selection. CONCLUSIONS: We have identified three avian FOXE1 genes based on synteny and sequence similarity as well as characterized the expression pattern of the chicken FOXE1 gene during development. Our evolutionary analyses suggest that while a relaxed purifying selection is likely to be the dominant force driving accelerated evolution of avian FOXE1 genes, a few residues may have evolved adaptively. This study provides a basis for future genetic and comparative biochemical studies of FOXE1.


Asunto(s)
Pollos/genética , Evolución Molecular , Pinzones/genética , Factores de Transcripción Forkhead/genética , Selección Genética , Pavos/genética , Región de Flanqueo 3'/genética , Animales , Secuencia de Bases , Cartilla de ADN/genética , Plumas/crecimiento & desarrollo , Plumas/metabolismo , Factores de Transcripción Forkhead/metabolismo , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Eliminación de Secuencia , Glándula Tiroides/crecimiento & desarrollo , Glándula Tiroides/metabolismo
17.
BMC Dev Biol ; 11: 20, 2011 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-21418646

RESUMEN

BACKGROUND: FGF signalling regulates numerous aspects of early embryo development. During gastrulation in amniotes, epiblast cells undergo an epithelial to mesenchymal transition (EMT) in the primitive streak to form the mesoderm and endoderm. In mice lacking FGFR1, epiblast cells in the primitive streak fail to downregulate E-cadherin and undergo EMT, and cell migration is inhibited. This study investigated how FGF signalling regulates cell movement and gene expression in the primitive streak of chicken embryos. RESULTS: We find that pharmacological inhibition of FGFR activity blocks migration of cells through the primitive streak of chicken embryos without apparent alterations in the level or intracellular localization of E-cadherin. E-cadherin protein is localized to the periphery of epiblast, primitive streak and some mesodermal cells. FGFR inhibition leads to downregulation of a large number of regulatory genes in the preingression epiblast adjacent to the primitive streak, the primitive streak and the newly formed mesoderm. This includes members of the FGF, NOTCH, EPH, PDGF, and canonical and non-canonical WNT pathways, negative modulators of these pathways, and a large number of transcriptional regulatory genes. SNAI2 expression in the primitive streak and mesoderm is not altered by FGFR inhibition, but is downregulated only in the preingression epiblast region with no significant effect on E-cadherin. Furthermore, over expression of SNAIL has no discernable effect on E-cadherin protein levels or localization in epiblast, primitive streak or mesodermal cells. FGFR activity modulates distinct downstream pathways including RAS/MAPK and PI3K/AKT. Pharmacological inhibition of MEK or AKT indicate that these downstream effectors control discrete and overlapping groups of genes during gastrulation. FGFR activity regulates components of several pathways known to be required for cell migration through the streak or in the mesoderm, including RHOA, the non-canonical WNT pathway, PDGF signalling and the cell adhesion protein N-cadherin. CONCLUSIONS: In chicken embryos, FGF signalling regulates cell movement through the primitive streak by mechanisms that appear to be independent of changes in E-cadherin expression or protein localization. The positive and negative effects on large groups of genes by pharmacological inhibition of FGF signalling, including major signalling pathways and transcription factor families, indicates that the FGF pathway is a focal point of regulation during gastrulation in chicken.


Asunto(s)
Cadherinas/genética , Movimiento Celular , Factores de Crecimiento de Fibroblastos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Primitiva/metabolismo , Proteínas ras/metabolismo , Animales , Western Blotting , Cadherinas/metabolismo , Embrión de Pollo , Electroporación , Factores de Crecimiento de Fibroblastos/genética , Gastrulación , Expresión Génica , Hibridación in Situ , Análisis por Micromatrices , Proteínas Quinasas Activadas por Mitógenos/genética , Fosfatidilinositol 3-Quinasas/genética , Reacción en Cadena de la Polimerasa , Línea Primitiva/embriología , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Factores de Transcripción de la Familia Snail , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas ras/genética
18.
Dev Dyn ; 239(6): 1879-87, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20503383

RESUMEN

The Krüppel-like transcription factors (KLF) are zinc finger proteins that activate and suppress target gene transcription. Although KLF factors have been implicated in regulating many developmental processes, a comprehensive gene expression analysis has not been reported. Here we present the chicken KLF gene family and expression during the first five days of embryonic development. Fourteen chicken KLF genes or expressed sequences have been previously identified. Through synteny analysis and cDNA mapping, we have identified the KLF9 gene and determined that the gene presently named KLF1 is the true ortholog of KLF17 in other species. In situ hybridization expression analyses show that in general KLFs are broadly expressed in multiple cell and tissue types. Expression of KLFs 3, 7, 8, and 9, is widespread at all stages examined. KLFs 2, 4, 5, 6, 10, 11, 15, and 17 show more restricted patterns that suggest multiple functions during early stages of embryonic development.


Asunto(s)
Pollos/genética , Factores de Transcripción , Animales , Secuencia de Bases , Embrión de Pollo , Pollos/metabolismo , Embrión no Mamífero , Femenino , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Dedos de Zinc/genética
20.
Nat Ecol Evol ; 4(9): 1239-1246, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32601391

RESUMEN

Among amniotes, reptiles and mammals are differently adapted to terrestrial life. It is generally appreciated that terrestrialization required adaptive changes of vertebrate metabolism, particularly in the mode of nitrogen excretion. However, the current paradigm is that metabolic adaptation to life on land did not involve synthesis of enzymatic pathways de novo, but rather repurposing of existing ones. Here, by comparing the inventory of pyridoxal 5'-phosphate-dependent enzymes in different amniotes, we identify in silico a pathway for sulfur metabolism present in chick embryos but not in mammals. Cysteine lyase contains haem and pyridoxal 5'-phosphate co-factors and converts cysteine and sulfite into cysteic acid and hydrogen sulfide, respectively. A specific cysteic acid decarboxylase produces taurine, while hydrogen sulfide is recycled into cysteine by cystathionine beta-synthase. This reaction sequence enables the formation of sulfonated amino acids during embryo development in the egg at no cost of reduced sulfur. The pathway originated around 300 million years ago in a proto-reptile by cystathionine beta-synthase duplication, cysteine lyase neofunctionalization and cysteic acid decarboxylase co-option. Our findings indicate that adaptation to terrestrial life involved innovations in metabolic pathways, and reveal the molecular mechanisms by which such innovations arose in amniote evolution.


Asunto(s)
Cistationina gamma-Liasa , Sulfuro de Hidrógeno , Animales , Embrión de Pollo , Cistationina betasintasa/genética , Cisteína , Azufre
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