RESUMO
Neu-Laxova syndrome (NLS) is a lethal genetic multiple congenital anomaly syndrome of unknown prevalence representing the severe spectrum of serine biosynthesis defects associated with PHGDH, PSAT1, or PSP gene mutations. The purpose of this study was to describe clinical/molecular and pathologic features of a NLS case caused by novel heterozygous missense variant in PHGDH gene identified in his consanguineous parents.
Assuntos
Anormalidades Múltiplas/genética , Encefalopatias/genética , Anormalidades Congênitas/genética , Retardo do Crescimento Fetal/genética , Ictiose/genética , Deformidades Congênitas dos Membros/genética , Microcefalia/genética , Fosfoglicerato Desidrogenase/genética , Natimorto/genética , Anormalidades Múltiplas/mortalidade , Anormalidades Múltiplas/patologia , Encefalopatias/mortalidade , Encefalopatias/patologia , Brasil/epidemiologia , Anormalidades Congênitas/mortalidade , Anormalidades Congênitas/patologia , Consanguinidade , Feminino , Retardo do Crescimento Fetal/mortalidade , Retardo do Crescimento Fetal/patologia , Genes Letais/genética , Predisposição Genética para Doença , Humanos , Ictiose/mortalidade , Ictiose/patologia , Deformidades Congênitas dos Membros/mortalidade , Deformidades Congênitas dos Membros/patologia , Microcefalia/mortalidade , Microcefalia/patologia , Mutação de Sentido Incorreto/genética , Gravidez , Natimorto/epidemiologiaRESUMO
Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT) is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.
Ao longo das duas últimas décadas, morbidade e mortalidade da malária e dengue e outros patógenos tem se tornado cada vez mais um problema de Saúde Pública. O aumento na distribuição geográfica de seus respectivos vetores é acompanhada pela emergência de doenças em novas áreas. Não estão disponíveis drogas específicas suficientes e não há vacinas específicas para imunizar as populações alvo. As medidas de controle de mosquitos atuais falharam em atingir os objetivos propostos, principalmente devido à grande capacidade reprodutiva dos mosquitos e alta flexibilidade genômica. O controle químico se torna cada vez mais restrito devido a sua potencial toxicidade aos seres humanos, mortalidade de organismos não alvos, resistência a inseticida além de outros impactos ambientais. Novas estratégias de controle são necessárias. A técnica do inseto estéril (SIT) é um método de supressão populacional espécie específico e ambientalmente amigável, baseia-se na criação em massa, esterilização mediante irradiação e liberação de um grande número de insetos machos. Liberar insetos carregando um gene letal dominante (RIDL) oferece uma solução a muitas limitações impostas pela técnica do inseto estéril (SIT) que limitaram sua aplicação em mosquitos e ainda assim mantém suas características de ambientalmente amigável e espécie específica. A natureza auto-limitante de mosquitos estéreis tende a deixar alguns empecilhos para uso no campo, de certa forma, menos desafiadores quando comparados a sistemas auto-propagação, característicos de estratégias de substituição de população. Sistemas auto-limitantes estão mais próximos para uso no campo, portanto pode ser apropriado considerá-lo primeiro. A perspectiva de métodos de controle genéticos contra mosquitos vetores de doenças que acometem humanos está rapidamente se tornando uma realidade, muitas decisões terão de ser tomadas em âmbito nacional, regional e internacional com relação a aspectos étnicos, sociais, culturais e de biossegurança para o uso e liberação destes métodos de controle de vetores.
Assuntos
Animais , Feminino , Masculino , Culicidae/genética , Genes Letais/genética , Insetos Vetores/genética , Controle de Mosquitos/métodos , Culicidae/fisiologia , Insetos Vetores/fisiologiaRESUMO
Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT) is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.
Assuntos
Culicidae/genética , Genes Letais/genética , Insetos Vetores/genética , Controle de Mosquitos/métodos , Animais , Culicidae/fisiologia , Feminino , Insetos Vetores/fisiologia , MasculinoAssuntos
Aedes/crescimento & desenvolvimento , Aedes/genética , Controle de Insetos/métodos , Aedes/metabolismo , Animais , Animais Geneticamente Modificados , Simulação por Computador , Genes Letais/genética , Marcadores Genéticos/genética , Larva/química , Larva/genética , Proteínas Luminescentes/genética , Masculino , Índias Ocidentais , Proteína Vermelha FluorescenteRESUMO
Biological invasions are excellent opportunities to study the evolutionary forces leading to the adaptation of a species to a new habitat. Knowledge of the introduction history of colonizing species helps tracking colonizing routes and assists in defining management strategies for invasive species. The Palearctic species Drosophila subobscura is a good model organism for tracking colonizations since it was detected in Chile and western North America three decades ago and later on in the Atlantic coast of Argentina. To unravel the origin of the Argentinean colonizers two populations have been analysed with several genetic markers. Chromosomal arrangements and microsatellite alleles found in Argentina are almost similar to those observed in Chile and USA. The lethal allelism test demonstrates that the lethal gene associated with the O(5) inversions in Argentina is identical to that found in Chile and USA, strongly supporting the hypothesis that all the American colonizing populations originated from the same colonization event. A secondary bottleneck is detected in the Argentinean populations and the genetic markers suggest that these populations originated from the invasion of 80-150 founding individuals from Chile.
Assuntos
Migração Animal , Drosophila/fisiologia , Animais , Argentina , Cromossomos/genética , Drosophila/classificação , Genes Letais/genética , Genética Populacional , Repetições de Microssatélites/genética , FilogeniaRESUMO
The putative translation initiation factor 5A (eIF5A) is a small protein, highly conserved and essential in all organisms from archaea to mammals. Although the involvement of eIF5A in translation initiation has been questioned, new evidence reestablished the connection between eIF5A and this cellular process. In order to better understand the function of elF5A, a screen for synthetic lethal gene using the tif51A-3 mutant was carried out and a new mutation (G80D) was found in the essential gene YPT1, encoding a protein involved in vesicular trafficking. The precursor form of the vacuolar protein CPY is accumulated in the ypt1-G80D mutant at the nonpermissive temperature, but this defect in vesicular trafficking did not occur in the tif51A mutants tested. Overexpression of eIF5A suppresses the growth defect of a series of ypt1 mutants, but this suppression does not restore correct CPY sorting. On the other hand, overexpression of YPT1 does not suppress the growth defect of tif51A mutants. Further, it was revealed that eIF-5A is present in both soluble and membrane fractions, and its membrane association is ribosome-dependent. Finally, we demonstrated that the ypt1 and other secretion pathway mutants are sensitive to paromomycin. These results confirm the link between translation and vesicular trafficking and reinforce the implication of eIF5A in protein synthesis.
Assuntos
Genes Letais/genética , Fatores de Iniciação de Peptídeos/genética , Biossíntese de Proteínas , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Vesículas Secretórias/metabolismo , Proteínas rab de Ligação ao GTP/genética , Alelos , Transporte Biológico , Carboxipeptidases/metabolismo , Genes Fúngicos , Membranas Intracelulares/metabolismo , Modelos Genéticos , Proteínas Mutantes/metabolismo , Mutação/genética , Processamento de Proteína Pós-Traducional , Ribossomos/metabolismo , Saccharomyces cerevisiae/citologia , Proteínas de Saccharomyces cerevisiae/metabolismo , Supressão Genética , Temperatura , Fator de Iniciação de Tradução Eucariótico 5ARESUMO
The putative eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for cell viability and the only cellular protein known to contain the unusual amino acid residue hypusine. eIF5A has been implicated in translation initiation, cell proliferation, nucleocytoplasmic transport, mRNA decay, and actin polarization, but the precise biological function of this protein is not clear. However, eIF5A was recently shown to be directly involved with the translational machinery. A screen for synthetic lethal mutations was carried out with one of the temperature-sensitive alleles of TIF51A (tif51A-3) to identify factors that functionally interact with eIF5A and revealed the essential gene YPT1. This gene encodes a small GTPase, a member of the rab family involved with secretion, acting in the vesicular trafficking between endoplasmatic reticulum and the Golgi. Thus, the synthetic lethality between TIF51A and YPT1 may reveal the connection between translation and the polarized distribution of membrane components, suggesting that these proteins work together in the cell to guarantee proper protein synthesis and secretion necessary for correct bud formation during G1/S transition. Future studies will investigate the functional interaction between eIF5A and Ypt1 in order to clarify this involvement of eIF5A with vesicular trafficking.
Assuntos
Genes Letais/genética , Mutação/genética , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Proteínas rab de Ligação ao GTP/genética , Fase G1/genética , Fase S/genética , Saccharomyces cerevisiae/citologia , Vesículas Transportadoras/genética , Fator de Iniciação de Tradução Eucariótico 5ARESUMO
The putative eukaryotic translation initiation factor 5A (eIF5A) is an essential protein for cell viability and the only cellular protein known to contain the unusual amino acid residue hypusine. eIF5A has been implicated in translation initiation, cell proliferation, nucleocytoplasmic transport, mRNA decay, and actin polarization, but the precise biological function of this protein is not clear. However, eIF5A was recently shown to be directly involved with the translational machinery. A screen for synthetic lethal mutations was carried out with one of the temperature-sensitive alleles of TIF51A (tif51A-3) to identify factors that functionally interact with eIF5A and revealed the essential gene YPT1. This gene encodes a small GTPase, a member of the rab family involved with secretion, acting in the vesicular trafficking between endoplasmatic reticulum and the Golgi. Thus, the synthetic lethality between TIF51A and YPT1 may reveal the connection between translation and the polarized distribution of membrane components, suggesting that these proteins work together in the cell to guarantee proper protein synthesis and secretion necessary for correct bud formation during G1/S transition. Future studies will investigate the functional interaction between eIF5A and Ypt1 in order to clarify this involvement of eIF5A with vesicular trafficking.
Assuntos
Genes Letais/genética , Mutação/genética , Fatores de Iniciação de Peptídeos/genética , Proteínas de Ligação a RNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Proteínas rab de Ligação ao GTP/genética , Fase G1/genética , Fase S/genética , Saccharomyces cerevisiae/citologia , Vesículas Transportadoras/genéticaRESUMO
Dominant lethal effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) were evaluated in the freshwater snail Biomphalaria glabrata. Wild-type snails were exposed during 10 days to 50, 75 and 100ppm of 2,4-D dimethylamine salt (2,4-D DMA) and paired with non-exposed albino snails 1, 11, 25 and 40 days after the exposure. The offspring of the non-exposed albino snails was scored for lethal malformations. One day after the exposure, a significant effect was observed at 75 and 100ppm without a dose-response relationship. After 11 days, the effect was observed only at the highest dose. After 25 days, significant increases in the dominant lethal effects occurred at 50 and 75ppm; effects were directly related to the doses. Background levels of lethal malformations were resumed after 40 days. Although the major and direct measure of dominant lethal mutations is the rate of lethal malformations in the heterozygous offspring of the albino snails, the sensitivity of the assay was substantially increased with the evaluation of all non-viable embryos, that are the sum of those with lethal malformations, identified or not as wild-type.
Assuntos
Ácido 2,4-Diclorofenoxiacético/toxicidade , Biomphalaria/efeitos dos fármacos , Animais , Biomphalaria/embriologia , Biomphalaria/genética , Relação Dose-Resposta a Droga , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Feminino , Genes Dominantes/genética , Genes Letais/genética , Células Germinativas/efeitos dos fármacos , Células Germinativas/metabolismo , Células Germinativas/patologia , Herbicidas/toxicidade , Masculino , Testes de Mutagenicidade/métodos , Mutagênicos/toxicidade , Fatores de TempoRESUMO
In the axolotl, Ambystoma mexicanum, a simple, recessive cardiac-lethal mutation in gene "c" results in the hearts of c/c homozygous animals being deficient in sarcomeric tropomyosin (TM) and failing to form mature myofibrils. Subsequently, the mutant hearts do not beat. A three-step model of myofibril assembly recently developed in cell culture prompted a reassessment of the myofibril assembly process in mutant hearts using a relatively new late marker for thin filament assembly, tropomodulin (Tmod). This is, to the best of our knowledge, the first report of tropomodulin in an amphibian system. Tropomodulin antibodies were immunolocalized to the ends of the thin filaments. Tropomodulin was also found in discrete punctate spots in normal and mutant hearts, often in linear arrays suggestive of early myofibril formation. The tropomodulin spots assessed in stage 41/42 mutant hearts co-localized with antibodies to other myofibrillar proteins indicative of nascent myofibril formation. This suggests a failure of elongation/maturation of nascent myofibrils, which could be a consequence of decreased TM levels or increased Tmod/ TM ratio. Unlike tropomyosin, there is no apparent decrease in the level of Tmod expression in mutant hearts.
Assuntos
Genes Letais/genética , Coração/crescimento & desenvolvimento , Miocárdio/metabolismo , Tropomodulina/biossíntese , Tropomodulina/genética , Ambystoma , Animais , Anticorpos Monoclonais , Biomarcadores , Western Blotting , Eritrócitos/metabolismo , Imuno-Histoquímica , Microscopia Confocal , Mutação/fisiologia , Miofibrilas/patologia , Miofibrilas/fisiologia , Tropomodulina/deficiênciaRESUMO
The dominant lethal effects of gamma radiation of 60Co in the snail Biomphalaria glabrata were studied. Three groups of 13 wild-type snails were irradiated with single doses of 2.5; 10 and 20 Gy. Crossings were carried out at intervals of 7, 17, 23, 30 and 36 days after irradiation. The dominant lethal effect was observed only at the first crossing occurring 7 days after irradiation with 2.5 Gy. With 10 and 20 Gy, the induction of lethal mutations was detected at 7, 17 and 23 days after irradiation; a dose-response effect was observed. The effect was stronger 7 days after irradiation, decreasing in the succeeding crossings up to 30 days. Cell-killing effects on germ cells were detected in the crossings at 23 days and 30 days after irradiation with 20 Gy. After 36 days, frequencies of malformations resumed background levels; crossing rates partially recovered. These results show that gamma radiation affected all the stages of spermatogenesis. Germ cells at later phases were more sensitive to the mutagenic effect of radiation and the cell killing effects were observed on the youngest cells. This response was similar to the highly homogeneous pattern observed in widely different species and allowed us to estimate some parameters of spermatogenesis in B. glabrata.
Assuntos
Radioisótopos de Cobalto/toxicidade , Raios gama , Mutação/efeitos da radiação , Caramujos/efeitos da radiação , Fatores Etários , Animais , Cruzamentos Genéticos , Relação Dose-Resposta à Radiação , Embrião não Mamífero/efeitos da radiação , Genes Letais/genética , Masculino , Mutação/genética , Caramujos/genética , Espermatogênese/efeitos da radiação , Fatores de TempoRESUMO
Introducción. El síndrome hidroletal es una rara entidad autosómica recesiva caracterizada principalmente por polihidramnios, hidrocefalia, letalidad y polidactilia. La gran mayoría de estos casos han sido descritos en Finlandia con escasos reportes de dicho problema en otros países. Caso clínico. Se reporta un caso con características compatibles con síndrome hidroletal en una pareja no consanguínea, sin ancestros europeos en cuyo caso el recién nacido no fallece a las pocas horas.Conclusión. Este sería el primer caso de síndrome hidroletal reportado en Latinoamérica y su presentación ligeramente diferente podría ser una variante alélica de su similar finlandés.
Assuntos
Humanos , Feminino , Recém-Nascido , Anormalidades Congênitas/diagnóstico , Hidrocefalia/genética , Síndrome de Dandy-Walker/diagnóstico , Poli-Hidrâmnios , Polidactilia/genética , Equador , Genes Letais/genética , Doenças Genéticas InatasRESUMO
Se calcularon los porcientos de genes letales recesivos que en estado homocigótico, provocan mortalidad embrionaria tomando como base poblaciones de ratas y ratones no consanguíneos. El aporte de los genes letales recesivos se halló por la diferencia de la mortalidad embrionaria entre 2 grupos con diferentes variantes de apareamiento: sistema rotatorio y cruzamiento consanguíneo. Se comparó al efecto el número de cuerpos lúteos, fetos vivos y reabsorciones en 200 ratones y 160 ratas en los días 15 y 17 del embarazo. Solamente en las ratas se encontraron diferencias significativas entre ambos sistemas debido al efecto de los genes letales recesivos. La mortalidad embrionaria después de la implantación y en general fue de 5,05 y 4,25 por ciento respectivamente(AU)
Assuntos
Animais , Camundongos , Ratos , Genes Letais/genética , Genes Recessivos/genética , Comportamento Sexual Animal , Animais de Laboratório/embriologiaRESUMO
Se calcularon los porcientos de genes letales recesivos que en estado homocigótico, provocan mortalidad embrionaria tomando como base poblaciones de ratas y ratones no consanguíneos. El aporte de los genes letales recesivos se halló por la diferencia de la mortalidad embrionaria entre 2 grupos con diferentes variantes de apareamiento: sistema rotatorio y cruzamiento consanguíneo. Se comparó al efecto el número de cuerpos lúteos, fetos vivos y reabsorciones en 200 ratones y 160 ratas en los días 15 y 17 del embarazo. Solamente en las ratas se encontraron diferencias significativas entre ambos sistemas debido al efecto de los genes letales recesivos. La mortalidad embrionaria después de la implantación y en general fue de 5,05 y 4,25 por ciento respectivamente
Assuntos
Animais , Camundongos , Ratos , Animais de Laboratório/embriologia , Genes Letais/genética , Genes Recessivos/genética , Comportamento Sexual AnimalRESUMO
Uma amostra de 59.496 indivíduos latino-americanos pertencentes a 28.545 irmandades foi tomada de um grande Estudo Colaborativo de Malformaçöes Congênitas (ECLAMC). Recém-nascidos com malformaçöes congênitas e seus respectivos controles foram excluídos da amostra com a finalidade de evitar vieses associados com malformaçöes. Alguns modelos estatísticos foram aplicados, admitindo-se que os efeitos de Poisson e de Markovian näo säo importantes na determinaçäo da distribuiçäo geral das irmandades na populaçäo. O modelo geral foi o binomial duplo com excesso unicaudal. Este modelo pode ser simplificado para o binomial duplo, o binomial simples com excesso unicaudal ou o binomial simples. As primeiras três distribuiçöes ajustaram-se aos dados. Os mesmos modelos foram aplicados a vários estudos realizados em diferentes países e em épocas diferentes, os quais apresentaram resultados semelhantes. O modelo mais parcimonioso que se ajustou à maioria dos conjuntos de dados foi o binomial duplo, sugerindo que cerca de 9 por cento dos casais segregam letais recessivos ligados ao X, uma vez que as duas proporçöes de segregaçäo do modelo estäo próximas da previsäo genética.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Criança , Adulto , Aberrações dos Cromossomos Sexuais/genética , Distribuição por Sexo , Distribuição Binomial , Genes Letais/genética , Cromossomo X/genéticaRESUMO
Thirty-three insertions of transposon Tn10 delta 16 delta 17 into genes involved in the control of rod cell shape were isolated in Salmonella typhimurium by the characteristic glossy appearance of colonies composed of spherical cells. Genetic tests demonstrated that 25 (76%) were insertions in the rodA gene, 7 (21%) were mre mutants, and 1 (3%) was a divD mutant. No insertion in the pbpA gene were found. Insertions in cell shape genes only appeared when strains displaying resistance to mecillinam (not caused by beta-lactamase production) were employed. Neither rodA nor mre insertions could be transduced to wild-type strains but they were normally accepted by mecillinam-resistant derivatives and by cya and crp mutants, which, unlike the corresponding Escherichia coli strains, did not display resistance to mecillinam. On the other hand, the divD insertion could be efficiently transduced to any strain. It is concluded that the rodA, mre, and divD genes are involved in the control of rod cell shape but, in addition, the RodA and Mre products perform some function(s) that is essential for wild-type cells but dispensable for some mecillinam-resistant strains, and for cya and crp mutants.
Assuntos
Proteínas de Escherichia coli , Genes Letais/genética , Proteínas de Membrana , Morfogênese/genética , Mutagênese Insercional , Salmonella typhimurium/genética , Andinocilina , Proteínas de Bactérias/genética , Elementos de DNA Transponíveis , Resistência Microbiana a Medicamentos , Salmonella typhimurium/citologia , Transdução GenéticaRESUMO
Recent studies on avian and mammalian embryos have established that the epicardium is derived, not from the early heart tube, but from mesothelial tissue overlying the sinus venosus. We tested the validity of this concept for Amphibia by examining normal and cardiac lethal (c/c) mutant axolotl embryos (stages 35-43) by electron microscopy. In axolotl embryos, the myocardial surface of the heart remains exposed to the pericardial fluid through stage 39. At this stage the transverse septum releases into the pericardial cavity mesothelial cells that subsequently flatten over the adjacent ventricular myocardium. However, mesothelial cells observed on the developing epicardium always appear rounded and may extend a filopodium up to 75 microns. This apparent "substrate-dependent" difference in mesothelial cell shape may promote the extension of the epicardium over the rest of the myocardium. The initial site of epicardial formation persists in the adult as the ventricular pericardial stalk that connects the epicardium to the peritoneal lining of the transverse septum. Cardiac lethal (c/c) mutant embryos, despite the non-contractility of their myocardia, form their epicardia in the same way. This suggests that the c/c mutation does not impair those properties of the myocardium that render it a suitable substrate for epicardial spreading. The abnormal pattern of epicardial coverage of the edematous stage 41 c/c mutant heart could be the result of its abnormally large myocardial surface area, the abnormal proximity of the atrium to the transverse septum, and/or the absence of heart contractions which could aid the dispersion of mesothelial cells within the pericardial cavity. Despite species differences, epicardial development in the axolotl is similar to the general pattern described for higher vertebrate embryos.