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1.
PLoS One ; 19(7): e0306614, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38976656

RESUMO

Pigment patterns are incredibly diverse across vertebrates and are shaped by multiple selective pressures from predator avoidance to mate choice. A common pattern across fishes, but for which we know little about the underlying mechanisms, is repeated melanic vertical bars. To understand the genetic factors that modify the level or pattern of vertical barring, we generated a genetic cross of 322 F2 hybrids between two cichlid species with distinct barring patterns, Aulonocara koningsi and Metriaclima mbenjii. We identify 48 significant quantitative trait loci that underlie a series of seven phenotypes related to the relative pigmentation intensity, and four traits related to patterning of the vertical bars. We find that genomic regions that generate variation in the level of eumelanin produced are largely independent of those that control the spacing of vertical bars. Candidate genes within these intervals include novel genes and those newly-associated with vertical bars, which could affect melanophore survival, fate decisions, pigment biosynthesis, and pigment distribution. Together, this work provides insights into the regulation of pigment diversity, with direct implications for an animal's fitness and the speciation process.


Assuntos
Ciclídeos , Melaninas , Locos de Características Quantitativas , Animais , Ciclídeos/genética , Ciclídeos/metabolismo , Melaninas/metabolismo , Melaninas/genética , Pigmentação/genética , Fenótipo , Masculino , Feminino
2.
Evol Dev ; 26(1): e12461, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37850843

RESUMO

A central question in biology is the molecular origins of phenotypic diversity. While genetic changes are key to the genotype-phenotype relationship, alterations to chromatin structure and the physical packaging of histone proteins may also be important drivers of vertebrate divergence. We investigate the impact of such an epigenetic mechanism, histone acetylation, within a textbook example of an adaptive radiation. Cichlids of Lake Malawi have adapted diverse craniofacial structures, and here we investigate how histone acetylation influences morphological variation in these fishes. Specifically, we assessed the effect of inhibiting histone deacetylation using the drug trichostatin A (TSA) on developing facial structures. We examined this during three critical developmental windows in two cichlid species with alternate adult morphologies. Exposure to TSA during neural crest cell (NCC) migration and as postmigratory NCCs proliferate in the pharyngeal arches resulted in significant changes in lateral and ventral shape in Maylandia, but not in Tropheops. This included an overall shortening of the head, widening of the lower jaw, and steeper craniofacial profile, all of which are paedomorphic morphologies. In contrast, treatment with TSA during early chondrogenesis did not result in significant morphological changes in either species. Together, these data suggest a sensitivity to epigenetic alterations that are both time- and species-dependent. We find that morphologies are due to nonautonomous or potentially indirect effects on NCC development, including in part a global developmental delay. Our research bolsters the understanding that proper histone acetylation is essential for early craniofacial development and identifies a species-specific robustness to developmental change. Overall, this study demonstrates how epigenetic regulation may play an important role in both generating and buffering morphological variation.


Assuntos
Epigênese Genética , Histonas , Animais , Fenótipo , Arcada Osseodentária , Cromatina
3.
bioRxiv ; 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37461734

RESUMO

Pigment patterns are incredibly diverse across vertebrates and are shaped by multiple selective pressures from predator avoidance to mate choice. A common pattern across fishes, but for which we know little about the underlying mechanisms, is repeated melanic vertical bars. In order to understand genetic factors that modify the level or pattern of vertical barring, we generated a genetic cross of 322 F2 hybrids between two cichlid species with distinct barring patterns, Aulonocara koningsi and Metriaclima mbenjii. We identify 48 significant quantitative trait loci that underlie a series of seven phenotypes related to the relative pigmentation intensity, and four traits related to patterning of the vertical bars. We find that genomic regions that generate variation in the level of eumelanin produced are largely independent of those that control the spacing of vertical bars. Candidate genes within these intervals include novel genes and those newly-associated with vertical bars, which could affect melanophore survival, fate decisions, pigment biosynthesis, and pigment distribution. Together, this work provides insights into the regulation of pigment diversity, with direct implications for an animal's fitness and the speciation process.

4.
Mol Ecol ; 32(14): 3975-3988, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37161914

RESUMO

Divergence in body shape is one of the most widespread and repeated patterns of morphological variation in fishes and is associated with habitat specification and swimming mechanics. Such ecological diversification is the first stage of the explosive adaptive radiation of cichlid fishes in the East African Rift Lakes. We use two hybrid crosses of cichlids (Metriaclima sp. × Aulonocara sp. and Labidochromis sp. × Labeotropheus sp., >975 animals total) to determine the genetic basis of body shape diversification that is similar to benthic-pelagic divergence across fishes. Using a series of both linear and geometric shape measurements, we identified 34 quantitative trait loci (QTL) that underlie various aspects of body shape variation. These QTL are spread throughout the genome, each explaining 3.2-8.6% of phenotypic variation, and are largely modular. Further, QTL are distinct both between these two crosses of Lake Malawi cichlids and compared to previously identified QTL for body shape in fishes such as sticklebacks. We find that body shape is controlled by many genes of small effect. In all, we find that convergent body shape phenotypes commonly observed across fish clades are most likely due to distinct genetic and molecular mechanisms.


Assuntos
Ciclídeos , Somatotipos , Animais , Locos de Características Quantitativas/genética , Ecossistema , Fenótipo , Lagos
5.
Genes (Basel) ; 14(3)2023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36980813

RESUMO

Phelan-McDermid syndrome (PMS) is a multisystem disorder that is associated with deletions of the 22q13 genomic region or pathogenic variants in the SHANK3 gene. Notable features include developmental issues, absent or delayed speech, neonatal hypotonia, seizures, autism or autistic traits, gastrointestinal problems, renal abnormalities, dolichocephaly, and both macro- and microcephaly. Assessment of the genetic factors that are responsible for abnormal head size in PMS has been hampered by small sample sizes as well as a lack of attention to these features. Therefore, this study was conducted to investigate the relationship between head size and genes on chromosome 22q13. A review of the literature was conducted to identify published cases of 22q13 deletions with information on head size to conduct a pooled association analysis. Across 56 studies, we identified 198 cases of PMS with defined deletion sizes and head size information. A total of 33 subjects (17%) had macrocephaly, 26 (13%) had microcephaly, and 139 (70%) were normocephalic. Individuals with macrocephaly had significantly larger genomic deletions than those with microcephaly or normocephaly (p < 0.0001). A genomic region on 22q13.31 was found to be significantly associated with macrocephaly with CELSR1, GRAMD4, and TBCD122 suggested as candidate genes. Investigation of these genes will aid the understanding of head and brain development.


Assuntos
Transtornos Cromossômicos , Microcefalia , Recém-Nascido , Humanos , Microcefalia/genética , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Deleção Cromossômica , Estruturas Cromossômicas , Proteínas Mitocondriais/genética
6.
Semin Cell Dev Biol ; 145: 42-51, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-35718684

RESUMO

Vertebrates have some of the most complex and diverse features in animals, from varied craniofacial morphologies to colorful pigmentation patterns and elaborate social behaviors. All of these traits have their developmental origins in a multipotent embryonic lineage of neural crest cells. This "fourth germ layer" is a vertebrate innovation and the source of a wide range of adult cell types. While others have discussed the role of neural crest cells in human disease and animal domestication, less is known about their role in contributing to adaptive changes in wild populations. Here, we review how variation in the development of neural crest cells and their derivatives generates considerable phenotypic diversity in nature. We focus on the broad span of traits under natural and sexual selection whose variation may originate in the neural crest, with emphasis on behavioral factors such as intraspecies communication that are often overlooked. In all, we encourage the integration of evolutionary ecology with developmental biology and molecular genetics to gain a more complete understanding of the role of this single cell type in trait covariation, evolutionary trajectories, and vertebrate diversity.


Assuntos
Evolução Biológica , Crista Neural , Adulto , Animais , Humanos , Fenótipo , Pigmentação , Comportamento Social
7.
Biology (Basel) ; 11(8)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-36009792

RESUMO

Since Darwin, biologists have sought to understand the evolution and origins of phenotypic adaptations. The skull is particularly diverse due to intense natural selection on feeding biomechanics. We investigated the genetic and molecular origins of trophic adaptation using Lake Malawi cichlids, which have undergone an exemplary evolutionary radiation. We analyzed morphological differences in the lateral and ventral head shape among an insectivore that eats by suction feeding, an obligate biting herbivore, and their F2 hybrids. We identified variation in a series of morphological traits-including mandible width, mandible length, and buccal length-that directly affect feeding kinematics and function. Using quantitative trait loci (QTL) mapping, we found that many genes of small effects influence these craniofacial adaptations. Intervals for some traits were enriched in genes related to potassium transport and sensory systems, the latter suggesting co-evolution of feeding structures and sensory adaptations for foraging. Despite these indications of co-evolution of structures, morphological traits did not show covariation. Furthermore, phenotypes largely mapped to distinct genetic intervals, suggesting that a common genetic basis does not generate coordinated changes in shape. Together, these suggest that craniofacial traits are mostly inherited as separate modules, which confers a high potential for the evolution of morphological diversity. Though these traits are not restricted by genetic pleiotropy, functional demands of feeding and sensory structures likely introduce constraints on variation. In all, we provide insights into the quantitative genetic basis of trophic adaptation, identify mechanisms that influence the direction of morphological evolution, and provide molecular inroads to craniofacial variation.

8.
Methods Mol Biol ; 2082: 211-229, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31849018

RESUMO

Quantitative trait loci (QTL) are genetic regions that influence phenotypic variation of a complex trait, often through genetic interactions with each other and the environment. These are commonly identified through a statistical genetic analysis known as QTL mapping. Here, I present a step-by-step, practical approach to QTL mapping along with a sample data file. I focus on methods commonly used and discoveries that have been made in fishes, and utilize a multiple QTL mapping (MQM) approach in the free software package R/qtl.


Assuntos
Mapeamento Cromossômico , Locos de Características Quantitativas , Alelos , Biologia Computacional/métodos , Epistasia Genética , Ligação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Software
9.
Commun Biol ; 1: 55, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271938

RESUMO

Elasmoid scales are the most common epithelial appendage among vertebrates, however an understanding of the genetic mechanisms that underlie variation in scale shape is lacking. Using an F2 mapping cross between morphologically distinct cichlid species, we identified >40 QTL for scale shape at different body positions. We show that while certain regions of the genome regulate variation in multiple scales, most are specific to scales at distinct positions. This suggests a degree of regional modularity in scale development. We also identified a single QTL for variation in scale shape disparity across the body. Finally, we screened a QTL hotspot for candidate loci, and identified the Fgf receptor fgfr1b as a prime target. Quantitative rtPCR and small molecule manipulation support a role for Fgf signaling in shaping cichlid scales. While Fgfs have previously been implicated in scale loss, these data reveal new roles for the pathway in scale shape variation.

10.
Dev Biol ; 415(2): 338-346, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-26719128

RESUMO

We have made great strides towards understanding the etiology of craniofacial disorders, especially for 'simple' Mendelian traits. However, the facial skeleton is a complex trait, and the full spectrum of genetic, developmental, and environmental factors that contribute to its final geometry remain unresolved. Forward genetic screens are constrained with respect to complex traits due to the types of genes and alleles commonly identified, developmental pleiotropy, and limited information about the impact of environmental interactions. Here, we discuss how studies in an evolutionary model - African cichlid fishes - can complement traditional approaches to understand the genetic and developmental origins of complex shape. Cichlids exhibit an unparalleled range of natural craniofacial morphologies that model normal human variation, and in certain instances mimic human facial dysmorphologies. Moreover, the evolutionary history and genomic architecture of cichlids make them an ideal system to identify the genetic basis of these phenotypes via quantitative trait loci (QTL) mapping and population genomics. Given the molecular conservation of developmental genes and pathways, insights from cichlids are applicable to human facial variation and disease. We review recent work in this system, which has identified lbh as a novel regulator of neural crest cell migration, determined the Wnt and Hedgehog pathways mediate species-specific bone morphologies, and examined how plastic responses to diet modulate adult facial shapes. These studies have not only revealed new roles for existing pathways in craniofacial development, but have identified new genes and mechanisms involved in shaping the craniofacial skeleton. In all, we suggest that combining work in traditional laboratory and evolutionary models offers significant potential to provide a more complete and comprehensive picture of the myriad factors that are involved in the development of complex traits.


Assuntos
Ciclídeos/embriologia , Anormalidades Craniofaciais/embriologia , Modelos Animais de Doenças , Doenças dos Peixes/embriologia , Interação Gene-Ambiente , Cabeça/anatomia & histologia , Desenvolvimento Maxilofacial/fisiologia , Animais , Evolução Biológica , Ciclídeos/anatomia & histologia , Ciclídeos/genética , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/veterinária , Embrião não Mamífero/patologia , Desenvolvimento Embrionário , Comportamento Alimentar , Regulação da Expressão Gênica no Desenvolvimento , Pleiotropia Genética , Cabeça/embriologia , Humanos , Desenvolvimento Maxilofacial/genética , Crista Neural/embriologia , Fenótipo , Locos de Características Quantitativas , Transdução de Sinais , Especificidade da Espécie , Transativadores/genética
11.
Evodevo ; 6: 25, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26225206

RESUMO

BACKGROUND: A major goal of evolutionary biology is to understand the origins of phenotypic diversity. Changes in development, for instance heterochrony, can be a potent source of phenotypic variation. On the other hand, development can also constrain the spectrum of phenotypes that can be produced. In order to understand these dual roles of development in evolution, we examined the developmental trajectory of a trait central to the extensive adaptive radiation of East African cichlid fishes: craniofacial adaptations that allow optimal exploitation of ecological niches. Specifically, we use geometric morphometric analysis to compare morphological ontogenies among six species of Lake Malawi cichlids (n > 500 individuals) that span a major ecomorphological axis. We further evaluate how modulation of Wnt signaling impacts the long-term developmental trajectory of facial development. RESULTS: We find that, despite drastic differences in adult craniofacial morphologies, there are general similarities in the path of craniofacial ontogeny among species, suggesting that natural selection is working within a conserved developmental program. However, we also detect species-specific differences in the timing, direction, and/or duration of particular developmental trajectories, including evidence of heterochrony. Previous work in cichlids and other systems suggests that species-specific differences in adult morphology are due to changes in molecular signaling pathways that regulate early craniofacial development. In support of this, we demonstrate that modulation of Wnt signaling at early stages can shift a developmental trajectory into morphospace normally occupied by another species. However, without sustained modulation, craniofacial shape can recover by juvenile stages. This underscores the idea that craniofacial development is robust and that adult head shapes are the product of many molecular changes acting over extended periods of development. CONCLUSIONS: Our results are consistent with the hypothesis that development acts to both constrain and promote morphological diversity. They also illustrate the modular nature of the craniofacial skeleton and hence the ability of selection to act upon distinct anatomical features in an independent manner. We propose that trophic diversity among cichlids has been achieved via shifts in both specific (e.g., stage-specific changes in gene expression) and global (e.g., heterochrony) ontogenetic processes acting within a conserved developmental program.

12.
Mol Biol Evol ; 31(12): 3113-24, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25234704

RESUMO

Since the time of Darwin, biologists have sought to understand the origins and maintenance of life's diversity of form. However, the nature of the exact DNA mutations and molecular mechanisms that result in morphological differences between species remains unclear. Here, we characterize a nonsynonymous mutation in a transcriptional coactivator, limb bud and heart homolog (lbh), which is associated with adaptive variation in the lower jaw of cichlid fishes. Using both zebrafish and Xenopus, we demonstrate that lbh mediates migration of cranial neural crest cells, the cellular source of the craniofacial skeleton. A single amino acid change that is alternatively fixed in cichlids with differing facial morphologies results in discrete shifts in migration patterns of this multipotent cell type that are consistent with both embryological and adult craniofacial phenotypes. Among animals, this polymorphism in lbh represents a rare example of a coding change that is associated with continuous morphological variation. This work offers novel insights into the development and evolution of the craniofacial skeleton, underscores the evolutionary potential of neural crest cells, and extends our understanding of the genetic nature of mutations that underlie divergence in complex phenotypes.


Assuntos
Ciclídeos/genética , Proteínas de Peixes/genética , Crista Neural/citologia , Transativadores/genética , Adaptação Biológica , Animais , Movimento Celular , Ciclídeos/anatomia & histologia , Evolução Molecular , Feminino , Loci Gênicos , Arcada Osseodentária/anatomia & histologia , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Fenótipo , Filogenia , Xenopus laevis , Peixe-Zebra
13.
Mol Ecol ; 23(21): 5135-50, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25156298

RESUMO

Variation in pigmentation type and levels is a hallmark of myriad evolutionary radiations, and biologists have long been fascinated by the factors that promote and maintain variation in coloration across populations. Here, we provide insights into the genetic basis of complex and continuous patterns of colour variation in cichlid fishes, which offer a vast diversity of pigmentation patterns that have evolved in response to both natural and sexual selection. Specifically, we crossed two divergent cichlid species to generate an F2 mapping population that exhibited extensive variation in pigmentation levels and patterns. Our experimental design is robust in that it combines traditional quantitative trait locus (QTL) analysis with population genomics, which has allowed us to move efficiently from QTL interval to candidate gene. In total, we detected 41 QTL and 13 epistatic interactions that underlie melanocyte- and xanthophore-based coloration across the fins and flanks of these fishes. We also identified 2 QTL and 1 interaction for variation in the magnitude of integration among these colour traits. This finding in particular is notable as there are marked differences both within and between species with respect to the complexity of pigmentation patterns. While certain individuals are characterized by more uniform 'integrated' colour patterns, others exhibit many more degrees of freedom with respect to the distribution of colour 'modules' across the fins and flank. Our data reveal, for the first time, a genetic basis for this difference. Finally, we implicate pax3a as a mediator of continuous variation in the levels of xanthophore-based colour along the cichlid flank.


Assuntos
Ciclídeos/genética , Pigmentação/genética , Locos de Características Quantitativas , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Evolução Molecular , Feminino , Proteínas de Peixes/genética , Genética Populacional , Masculino , Fatores de Transcrição Box Pareados/genética , Fenótipo , Seleção Genética , Processos de Determinação Sexual
14.
Nat Commun ; 5: 3629, 2014 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-24699776

RESUMO

Progress towards understanding adaptive radiations at the mechanistic level is still limited with regard to the proximate molecular factors that both promote and constrain evolution. Here we focus on the craniofacial skeleton and show that expanded Wnt/ß-catenin signalling early in ontogeny is associated with the evolution of phenotypic novelty and ecological opportunity in Lake Malawi cichlids. We demonstrate that the mode of action of this molecular change is to effectively lock into place an early larval phenotype, likely through accelerated rates of bone deposition. However, we demonstrate further that this change toward phenotypic novelty may in turn constrain evolutionary potential through the corresponding reduction in craniofacial plasticity at later stages of ontogeny. In all, our data implicate the Wnt pathway as an important mediator of craniofacial form and offer new insights into how developmental systems can evolve to both promote and constrain evolutionary change.


Assuntos
Evolução Biológica , Ciclídeos/metabolismo , Proteínas de Peixes/metabolismo , Cabeça/crescimento & desenvolvimento , Transdução de Sinais , Proteínas Wnt/metabolismo , Animais , Ciclídeos/anatomia & histologia , Ciclídeos/genética , Ciclídeos/crescimento & desenvolvimento , Feminino , Proteínas de Peixes/genética , Cabeça/anatomia & histologia , Malaui , Masculino , Fenótipo , Proteínas Wnt/genética , beta Catenina/genética , beta Catenina/metabolismo
15.
PLoS One ; 7(4): e35111, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22523571

RESUMO

Higher vertebrates use similar genetic tools to derive very different facial features. This diversity is believed to occur through temporal, spatial and species-specific changes in gene expression within cranial neural crest (NC) cells. These contribute to the facial skeleton and contain species-specific information that drives morphological variation. A few signaling molecules and transcription factors are known to play important roles in these processes, but little is known regarding the role of micro-RNAs (miRNAs). We have identified and compared all miRNAs expressed in cranial NC cells from three avian species (chicken, duck, and quail) before and after species-specific facial distinctions occur. We identified 170 differentially expressed miRNAs. These include thirty-five novel chicken orthologs of previously described miRNAs, and six avian-specific miRNAs. Five of these avian-specific miRNAs are conserved over 120 million years of avian evolution, from ratites to galliforms, and their predicted target mRNAs include many components of Wnt signaling. Previous work indicates that mRNA gene expression in NC cells is relatively static during stages when the beak acquires species-specific morphologies. However, miRNA expression is remarkably dynamic within this timeframe, suggesting that the timing of specific developmental transitions is altered in birds with different beak shapes. We evaluated one miRNA:mRNA target pair and found that the cell cycle regulator p27(KIP1) is a likely target of miR-222 in frontonasal NC cells, and that the timing of this interaction correlates with the onset of phenotypic variation. Our comparative genomic approach is the first comprehensive analysis of miRNAs in the developing facial primordial, and in species-specific facial development.


Assuntos
Aves/genética , Animais , Evolução Biológica , Embrião de Galinha , Galinhas/genética , Patos/genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , MicroRNAs/genética , Crista Neural/embriologia , Osteogênese/genética , Codorniz/genética , Análise de Sequência de RNA , Via de Sinalização Wnt/genética
16.
J Neurosci ; 31(12): 4535-43, 2011 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-21430154

RESUMO

Sensory hair cells of the inner ear are the mechanoelectric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Nonmammalian vertebrates such as birds can regenerate hair cells after injury. In a previous study, we characterized transcription factor gene expression during chicken hair cell regeneration. In those studies, a laser microbeam or ototoxic antibiotics were used to damage the sensory epithelia (SE). The current study focused on 27 genes that were upregulated in regenerating SEs compared to untreated SEs in the previous study. Those genes were knocked down by siRNA to determine their requirement for supporting cell proliferation and to measure resulting changes in the larger network of gene expression. We identified 11 genes necessary for proliferation and also identified novel interactive relationships between many of them. Defined components of the WNT, PAX, and AP1 pathways were shown to be required for supporting cell proliferation. These pathways intersect on WNT4, which is also necessary for proliferation. Among the required genes, the CCAAT enhancer binding protein, CEBPG, acts downstream of Jun Kinase and JUND in the AP1 pathway. The WNT coreceptor LRP5 acts downstream of CEBPG, as does the transcription factor BTAF1. Both of these genes are also necessary for supporting cell proliferation. This is the first large-scale screen of its type and suggests an important intersection between the AP1 pathway, the PAX pathway, and WNT signaling in the regulation of supporting cell proliferation during inner ear hair cell regeneration.


Assuntos
Orelha Interna/fisiologia , Células Ciliadas Auditivas Internas/fisiologia , Regeneração Nervosa/fisiologia , Interferência de RNA/fisiologia , Fatores de Transcrição/genética , Animais , Fator de Ligação a CCAAT/genética , Fator de Ligação a CCAAT/fisiologia , Proliferação de Células , Galinhas , Epitélio/fisiologia , Técnicas de Silenciamento de Genes , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/fisiologia , Lasers , Análise em Microsséries , Paxilina/genética , Paxilina/fisiologia , Sáculo e Utrículo/fisiologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/fisiologia , Fator de Transcrição TFIID/genética , Fator de Transcrição TFIID/fisiologia , Proteínas Wnt/genética , Proteínas Wnt/farmacologia , Proteínas Wnt/fisiologia , Proteína Wnt4
17.
PLoS One ; 2(6): e525, 2007 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-17565378

RESUMO

Loss of inner ear sensory hair cells (HC) is a leading cause of human hearing loss and balance disorders. Unlike mammals, many lower vertebrates can regenerate these cells. We used cross-species microarrays to examine this process in the avian inner ear. Specifically, changes in expression of over 1700 transcription factor (TF) genes were investigated in hair cells of auditory and vestibular organs following treatment with two different damaging agents and regeneration in vitro. Multiple components of seven distinct known signaling pathways were clearly identifiable: TGFbeta, PAX, NOTCH, WNT, NFKappaB, INSULIN/IGF1 and AP1. Numerous components of apoptotic and cell cycle control pathways were differentially expressed, including p27(KIP) and TFs that regulate its expression. A comparison of expression trends across tissues and treatments revealed identical patterns of expression that occurred at identical times during regenerative proliferation. Network analysis of the patterns of gene expression in this large dataset also revealed the additional presence of many components (and possible network interactions) of estrogen receptor signaling, circadian rhythm genes and parts of the polycomb complex (among others). Equal numbers of differentially expressed genes were identified that have not yet been placed into any known pathway. Specific time points and tissues also exhibited interesting differences: For example, 45 zinc finger genes were specifically up-regulated at later stages of cochlear regeneration. These results are the first of their kind and should provide the starting point for more detailed investigations of the role of these many pathways in HC recovery, and for a description of their possible interactions.


Assuntos
Biomarcadores/metabolismo , Galinhas/genética , Células Epiteliais/fisiologia , Perfilação da Expressão Gênica , Células Ciliadas Auditivas Internas/fisiologia , Regeneração/fisiologia , Animais , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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