RESUMO
The paralogs 9-13 Hox genes in mouse HoxA and HoxD clusters are critical for limb development. When both HoxA and HoxD clusters are deleted in mice, significant limb truncation is observed compared to the phenotypes of single and compound mutants of Hox9-13 genes in these clusters. In zebrafish, mutations in hox13 genes in HoxA- and HoxD-related clusters result in abnormal morphology of pectoral fins, homologous to forelimbs. However, the effect of the simultaneous deletions of entire HoxA- and HoxD-related clusters on pectoral fin development remains unknown. Here, we generated mutants with several combinations of hoxaa, hoxab, and hoxda cluster deletions and analyzed the pectoral fin development. In hoxaa-/-;hoxab-/-;hoxda-/- larvae, the endoskeletal disc and the fin-fold are significantly shortened in developing pectoral fins. In addition, we show that this anomaly is due to defects in the pectoral fin growth after the fin bud formation. Furthermore, in the surviving adult mutants, micro-CT scanning reveals defects in the posterior portion of the pectoral fin which is thought to represent latent regions of the limb. Our results further support that the functional role of HoxA and HoxD clusters is conserved in the paired appendage formation in bony fishes.
Assuntos
Nadadeiras de Animais , Proteínas de Homeodomínio , Família Multigênica , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/genética , Nadadeiras de Animais/metabolismo , Nadadeiras de Animais/crescimento & desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , MutaçãoRESUMO
The origin of paired appendages became one of the most important adaptations of vertebrates, allowing them to lead active lifestyles and explore a wide range of ecological niches. The basic form of paired appendages in evolution is the fins of fishes. The problem of paired appendages has attracted the attention of researchers for more than 150 years. During this time, a number of theories have been proposed, mainly based on morphological data, two of which, the Balfour-Thacher-Mivart lateral fold theory and Gegenbaur's gill arch theory, have not lost their relevance. So far, however, none of the proposed ideas has been supported by decisive evidence. The study of the evolutionary history of the appearance and development of paired appendages lies at the intersection of several disciplines and involves the synthesis of paleontological, morphological, embryological, and genetic data. In this review, we attempt to summarize and discuss the results accumulated in these fields and to analyze the theories put forward regarding the prerequisites and mechanisms that gave rise to paired fins and limbs in vertebrates.
Assuntos
Nadadeiras de Animais , Evolução Biológica , Peixes , Animais , Nadadeiras de Animais/anatomia & histologia , Nadadeiras de Animais/crescimento & desenvolvimento , Peixes/anatomia & histologia , Peixes/genética , Peixes/crescimento & desenvolvimento , Peixes/embriologia , Vertebrados/anatomia & histologia , Vertebrados/crescimento & desenvolvimento , Vertebrados/genéticaRESUMO
The early development of the freshwater fish Rhytiodus microlepis is characterized by the description of external morphological, meristic, and morphometric changes, as well as the growth patterns, thereby establishing a reference for the identification of its larvae and juveniles. Specimens were collected from the Amazon river channel and floodplain. Ninety-seven individuals were analysed with standard length varying between 4.31 and 79.23 mm. Rhytiodus microlepis larvae are altricial, with an elongated and fusiform body, anal opening reaching the middle region of the body, and simple nostrils becoming double and tubular during development. The pigments vary from one to two chromatophores in the dorsal region of the head in pre-flexion and flexion, but later the pigmentation pattern intensifies, transverse bands appear along the body, and a conspicuous spot appears in the basal region of the caudal fin. The total number of myomeres ranges from 49 to 50. During the transition from larval (post-flexion) to the juvenile periods, the most significant anatomical changes occur, such as the presence of all fins and increased body pigmentation. Integrated myomere count and pigmentation pattern are effective for the correct identification of the initial life stages of R. microlepis from the Amazon basin. Our results expand the knowledge about the early life history of Neotropical freshwater fish species.
Assuntos
Caraciformes , Larva , Pigmentação , Rios , Animais , Caraciformes/crescimento & desenvolvimento , Caraciformes/anatomia & histologia , Brasil , Larva/crescimento & desenvolvimento , Larva/anatomia & histologia , Água Doce , Nadadeiras de Animais/anatomia & histologia , Nadadeiras de Animais/crescimento & desenvolvimentoRESUMO
Holocephalans exhibit auxiliary appendages called pre-pelvic claspers (PPCs) that are located anterior to the pelvic fins, while pelvic claspers are pelvic fin modifications located posteriorly as modified metapterygia. Articulation points of the PPCs have not previously been imaged or evaluated in a comparative context, therefore, they may represent modified pelvic fin structures if they articulate with the propterygium. Alternatively, they could represent the only example of an independent third set of paired appendages in an extant taxon, if they articulate independently from any pelvic fin basal cartilages, challenging the current paradigm that extant jawed vertebrates are constrained to two sets of paired appendages. Two extinct groups, including Placoderms and Acanthodians, exhibit variation in the number of paired appendages, suggesting this may be a plesiomorphic trait. We evaluated PPC developmental growth rates, morphology, and articulation points in spotted ratfish (Hydrolagus Colliei, Holocephali). We also compared variation in PPC morphology among representatives of the three extant holocephalan families. Both, the pre-pelvic and pelvic claspers exhibit a dramatic surge in growth at sexual maturity, and then level off, suggesting synchronous development via shared hormonal regulation. While mature females are larger than males, pelvic fin growth and development is faster in males, suggesting a selective advantage to larger fins with faster development. Finally, microcomputed tomography scans revealed that PPCs are not modified propterygia, nor do they articulate with the propterygium. They articulate with the anterior pre-pelvic process on the anterior puboischiadic bar (or pelvic girdle), suggesting that while they are associated with the pelvic girdle, they may indeed represent a third, independent set of paired appendages in extant holocephalans.
Assuntos
Nadadeiras de Animais , Peixes , Masculino , Feminino , Animais , Vertebrados/anatomia & histologia , Vertebrados/classificação , Vertebrados/fisiologia , Microtomografia por Raio-X , Peixes/anatomia & histologia , Peixes/classificação , Peixes/crescimento & desenvolvimento , Peixes/fisiologia , Nadadeiras de Animais/anatomia & histologia , Nadadeiras de Animais/crescimento & desenvolvimento , Pelve/anatomia & histologiaRESUMO
The development of paired appendages was a key innovation during evolution and facilitated the aquatic to terrestrial transition of vertebrates. Largely derived from the lateral plate mesoderm (LPM), one hypothesis for the evolution of paired fins invokes derivation from unpaired median fins via a pair of lateral fin folds located between pectoral and pelvic fin territories1. Whilst unpaired and paired fins exhibit similar structural and molecular characteristics, no definitive evidence exists for paired lateral fin folds in larvae or adults of any extant or extinct species. As unpaired fin core components are regarded as exclusively derived from paraxial mesoderm, any transition presumes both co-option of a fin developmental programme to the LPM and bilateral duplication2. Here, we identify that the larval zebrafish unpaired pre-anal fin fold (PAFF) is derived from the LPM and thus may represent a developmental intermediate between median and paired fins. We trace the contribution of LPM to the PAFF in both cyclostomes and gnathostomes, supporting the notion that this is an ancient trait of vertebrates. Finally, we observe that the PAFF can be bifurcated by increasing bone morphogenetic protein signalling, generating LPM-derived paired fin folds. Our work provides evidence that lateral fin folds may have existed as embryonic anlage for elaboration to paired fins.
Assuntos
Nadadeiras de Animais , Evolução Biológica , Mesoderma , Peixe-Zebra , Animais , Nadadeiras de Animais/anatomia & histologia , Nadadeiras de Animais/embriologia , Nadadeiras de Animais/crescimento & desenvolvimento , Larva/anatomia & histologia , Larva/crescimento & desenvolvimento , Mesoderma/anatomia & histologia , Mesoderma/embriologia , Mesoderma/crescimento & desenvolvimento , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/embriologia , Peixe-Zebra/crescimento & desenvolvimento , Proteínas Morfogenéticas Ósseas/metabolismoRESUMO
The pectoral fins of teleost fish are analogous structures to human forelimbs, and the developmental mechanisms directing their initial growth and patterning are conserved between fish and tetrapods. The forelimb vasculature is crucial for limb function, and it appears to play important roles during development by promoting development of other limb structures, but the steps leading to its formation are poorly understood. In this study, we use high-resolution imaging to document the stepwise assembly of the zebrafish pectoral fin vasculature. We show that fin vascular network formation is a stereotyped, choreographed process that begins with the growth of an initial vascular loop around the pectoral fin. This loop connects to the dorsal aorta to initiate pectoral vascular circulation. Pectoral fin vascular development continues with concurrent formation of three elaborate vascular plexuses, one in the distal fin that develops into the fin-ray vasculature and two near the base of the fin in association with the developing fin musculature. Our findings detail a complex, yet highly choreographed, series of steps involved in the development of a complete, functional, organ-specific vascular network.
Assuntos
Nadadeiras de Animais/anatomia & histologia , Nadadeiras de Animais/crescimento & desenvolvimento , Peixe-Zebra/anatomia & histologia , Peixe-Zebra/crescimento & desenvolvimento , AnimaisRESUMO
Skeletal elements frequently associate with vasculature and somatosensory nerves, which regulate bone development and homeostasis. However, the deep, internal location of bones in many vertebrates has limited in vivo exploration of the neurovascular-bone relationship. Here, we use the zebrafish caudal fin, an optically accessible organ formed of repeating bony ray skeletal units, to determine the cellular relationship between nerves, bones and endothelium. In adult zebrafish, we establish the presence of somatosensory axons running through the inside of the bony fin rays, juxtaposed with osteoblasts on the inner hemiray surface. During development we show that the caudal fin progresses through sequential stages of endothelial plexus formation, bony ray addition, ray innervation and endothelial remodeling. Surprisingly, the initial stages of fin morphogenesis proceed normally in animals lacking either fin endothelium or somatosensory nerves. Instead, we find that sp7+ osteoblasts are required for endothelial remodeling and somatosensory axon innervation in the developing fin. Overall, this study demonstrates that the proximal neurovascular-bone relationship in the adult caudal fin is established during fin organogenesis and suggests that ray-associated osteoblasts pattern axons and endothelium.
Assuntos
Nadadeiras de Animais/fisiologia , Axônios/metabolismo , Endotélio/metabolismo , Organogênese/fisiologia , Peixe-Zebra/crescimento & desenvolvimento , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Animais Geneticamente Modificados/crescimento & desenvolvimento , Animais Geneticamente Modificados/metabolismo , Endotélio/citologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Larva/crescimento & desenvolvimento , Larva/metabolismo , Osteoblastos/citologia , Osteoblastos/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Fator de Transcrição Sp7/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
One of the central problems of vertebrate evolution is understanding the relationship among the distal portions of fins and limbs. Lacking comparable morphological markers of these regions in fish and tetrapods, these relationships have remained uncertain for the past century and a half. Here we show that Gli3 functions in controlling the proliferative expansion of distal progenitors are shared among dorsal and paired fins as well as tetrapod limbs. Mutant knockout gli3 fins in medaka (Oryzias latipes) form multiple radials and rays, in a pattern reminiscent of the polydactyly observed in Gli3-null mutant mice. In limbs, Gli3 controls both anterior-posterior patterning and cell proliferation, two processes that can be genetically uncoupled. In situ hybridization, quantification of proliferation markers, and analysis of regulatory regions reveal that in paired and dorsal fins, gli3 plays a main role in controlling proliferation but not in patterning. Moreover, gli3 down-regulation in shh mutant fins rescues fin loss in a manner similar to how Gli3 deficiency restores digits in the limbs of Shh mutant mouse embryos. We hypothesize that the Gli3/Shh gene pathway preceded the origin of paired appendages and was originally involved in modulating cell proliferation. Accordingly, the distal regions of dorsal fins, paired fins, and limbs retain a deep regulatory and functional homology that predates the origin of paired appendages.
Assuntos
Nadadeiras de Animais/crescimento & desenvolvimento , Redes Reguladoras de Genes/genética , Proteínas do Tecido Nervoso/genética , Oryzias/genética , Proteína Gli3 com Dedos de Zinco/genética , Animais , Evolução Biológica , Padronização Corporal/genética , Proliferação de Células/genética , Extremidades/crescimento & desenvolvimento , Proteínas de Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , CamundongosRESUMO
Precise cis-regulatory control of gene expression is essential for normal embryogenesis and tissue development. The BMP antagonist Gremlin1 (Grem1) is a key node in the signalling system that coordinately controls limb bud development. Here, we use mouse reverse genetics to identify the enhancers in the Grem1 genomic landscape and the underlying cis-regulatory logics that orchestrate the spatio-temporal Grem1 expression dynamics during limb bud development. We establish that transcript levels are controlled in an additive manner while spatial regulation requires synergistic interactions among multiple enhancers. Disrupting these interactions shows that altered spatial regulation rather than reduced Grem1 transcript levels prefigures digit fusions and loss. Two of the enhancers are evolutionary ancient and highly conserved from basal fishes to mammals. Analysing these enhancers from different species reveal the substantial spatial plasticity in Grem1 regulation in tetrapods and basal fishes, which provides insights into the fin-to-limb transition and evolutionary diversification of pentadactyl limbs.
Assuntos
Nadadeiras de Animais/metabolismo , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica no Desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/genética , Botões de Extremidades/metabolismo , Nadadeiras de Animais/citologia , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Sequência de Bases , Evolução Biológica , Boidae , Bovinos , Galinhas , Embrião de Mamíferos , Embrião não Mamífero , Iguanas , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Botões de Extremidades/citologia , Botões de Extremidades/crescimento & desenvolvimento , Camundongos , Camundongos Transgênicos , Filogenia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Coelhos , Genética Reversa/métodos , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Tubarões , Transdução de Sinais , SuínosRESUMO
With over 18,000 species, the Acanthomorpha, or spiny-rayed fishes, form the largest and arguably most diverse radiation of vertebrates. One of the key novelties that contributed to their evolutionary success are the spiny rays in their fins that serve as a defense mechanism. We investigated the patterning mechanisms underlying the differentiation of median fin Anlagen into discrete spiny and soft-rayed domains during the ontogeny of the direct-developing cichlid fish Astatotilapia burtoni Distinct transcription factor signatures characterize these two fin domains, whereby mutually exclusive expression of hoxa13a/b with alx4a/b and tbx2b marks the spine to soft-ray boundary. The soft-ray domain is established by BMP inhibition via gremlin1b, which synergizes in the posterior fin with shh secreted from a zone of polarizing activity. Modulation of BMP signaling by chemical inhibition or gremlin1b CRISPR/Cas9 knockout induces homeotic transformations of spines into soft rays and vice versa. The expression of spine and soft-ray genes in nonacanthomorph fins indicates that a combination of exaptation and posterior expansion of an ancestral developmental program for the anterior fin margin allowed the evolution of robustly individuated spiny and soft-rayed domains. We propose that a repeated exaptation of such pattern might underly the convergent evolution of anterior spiny-fin elements across fishes.
Assuntos
Nadadeiras de Animais/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Ciclídeos/metabolismo , Proteínas de Peixes/metabolismo , Proteínas Hedgehog/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Evolução Biológica , Padronização Corporal , Proteínas Morfogenéticas Ósseas/genética , Ciclídeos/classificação , Ciclídeos/genética , Ciclídeos/crescimento & desenvolvimento , Proteínas de Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Filogenia , Transdução de Sinais , Coluna Vertebral/crescimento & desenvolvimento , Coluna Vertebral/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The increase in activity of the two-pore potassium-leak channel Kcnk5b maintains allometric juvenile growth of adult zebrafish appendages. However, it remains unknown how this channel maintains allometric growth and how its bioelectric activity is regulated to scale these anatomical structures. We show the activation of Kcnk5b is sufficient to activate several genes that are part of important development programs. We provide in vivo transplantation evidence that the activation of gene transcription is cell autonomous. We also show that Kcnk5b will induce the expression of different subsets of the tested developmental genes in different cultured mammalian cell lines, which may explain how one electrophysiological stimulus can coordinately regulate the allometric growth of diverse populations of cells in the fin that use different developmental signals. We also provide evidence that the post-translational modification of serine 345 in Kcnk5b by calcineurin regulates channel activity to scale the fin. Thus, we show how an endogenous bioelectric mechanism can be regulated to promote coordinated developmental signaling to generate and scale a vertebrate appendage.
Organs, limbs, fins and tails are made of multiple tissues whose growth is controlled by specific signals and genetic programmes. All these different cell populations must work together during development or regeneration to form a complete structure that is the right size in relation to the rest of the body. Growing evidence suggests that this synchronicity might be down to electric signals, which are created by movements of charged particles in and out of cells. In particular, previous work has identified two factors that control the development of fins in fish: the Kcnk5b potassium-leak channel, which allows positive ions to cross the cell membrane; and an enzyme called calcineurin, which can modify the activity of proteins. Kcnk5b and calcineurin seem to play similar roles in the proportional growth of the fins in relation to the body, but exactly how was unknown. To investigate this question, Yi et al. used genetically modified zebrafish to show how the Kcnk5b channel could control genes responsible for appendage growth. However, their tests on different cell types revealed that potassium movement through the Kcnk5b channel leads to different sets of developmental genes being turned on, depending on the tissue type of the cell. This could explain how one type of signal (in this case, movement of ions) can coordinate the growth of a wide range of tissues that use different combinations of developmental genes to form. Kcnk5b therefore appears to coordinate the regulation of the various combinations of genes needed for different fin tissues to develop, so that every component grows in a proportional, synchronized manner. Yi et al. also showed that calcineurin can modify the Kcnk5b channel to control its activity. In turn, this affects the movement of potassium ions across the membrane, changing electrical activity and, as a consequence, the proportional growth of the fin. Further work should explore how Kcnk5b and calcineurin link to other signals that regulate the size of fins and limbs. Ultimately, a finer understanding of the molecules controlling the growth of body parts will be useful in fields such as regenerative medicine or stem cell biology, which attempt to build organs for clinical therapies.
Assuntos
Nadadeiras de Animais/metabolismo , Calcineurina/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Canais de Potássio de Domínios Poros em Tandem/metabolismo , Potássio/metabolismo , Transcrição Gênica , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Nadadeiras de Animais/embriologia , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Animais Geneticamente Modificados , Calcineurina/genética , Feminino , Células HEK293 , Células HeLa , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Ativação do Canal Iônico , Masculino , Potenciais da Membrana , Morfogênese , Fosforilação , Canais de Potássio de Domínios Poros em Tandem/genética , Processamento de Proteína Pós-Traducional , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/genéticaRESUMO
The ontogeny of the paired appendages has been extensively studied in lungfishes and tetrapods, but remains poorly known in coelacanths. Recent work has shed light on the anatomy and development of the pectoral fin in Latimeria chalumnae. Yet, information on the development of the pelvic fin and girdle is still lacking. Here, we described the development of the pelvic fin and girdle in Latimeria chalumnae based on 3D reconstructions generated from conventional and X-ray synchrotron microtomography, as well as MRI acquisitions. As in other jawed vertebrates, the development of the pelvic fin occurs later than that of the pectoral fin in Latimeria. Many elements of the endoskeleton are not yet formed at the earliest stage sampled. The four mesomeres are already formed in the fetus, but only the most proximal radial elements (preaxial radial 0-1) are formed and individualized at this stage. We suggest that all the preaxial radial elements in the pelvic and pectoral fin of Latimeria are formed through the fragmentation of the mesomeres. We document the progressive ossification of the pelvic girdle, and the presence of a trabecular system in the adult. This trabecular system likely reinforces the cartilaginous girdle to resist the muscle forces exerted during locomotion. Finally, the presence of a preaxial element in contact with the pelvic girdle from the earliest stage of development onward questions the mono-basal condition of the pelvic fin in Latimeria. However, the particular shape of the mesomeres may explain the presence of this element in contact with the girdle.
Assuntos
Nadadeiras de Animais/crescimento & desenvolvimento , Evolução Biológica , Peixes/crescimento & desenvolvimento , Pelve/crescimento & desenvolvimento , Nadadeiras de Animais/diagnóstico por imagem , Animais , Fósseis , Imageamento por Ressonância Magnética , Pelve/diagnóstico por imagem , FilogeniaRESUMO
While it is well known that the notochord of bony fishes changes over developmental time, less is known about how it varies across different body regions. In the development of the Atlantic salmon, Salmo salar L., cranial and caudal ends of the notochord are overlaid by the formation of the bony elements of the neurocranium and caudal fin, respectively. To investigate, we describe how the notochord of the cranium and caudal fin changes from embryo to spawning adult, using light microscopy, SEM, TEM, dissection, and CT scanning. The differences are dramatic. In contrast to the abdominal and caudal regions, at the ends of the notochord vertebrae never develop. While the cranial notochord builds a tapering, unsegmented cone of chordal bone, the urostylic notochordal sheath never ossifies: adjacent, irregular bony elements form from the endoskeleton of the caudal fin. As development progresses, two previously undescribed processes occur. First, the bony cone of the cranial notochord, and its internal chordocytes, are degraded by chordoclasts, an undescribed function of the clastic cell type. Second, the sheath of the urostylic notochord creates transverse septae that partly traverse the lumen in an irregular pattern. By the adult stage, the cranial notochord is gone. In contrast, the urostylic notochord in adults is robust, reinforced with septae, covered by irregularly shaped pieces of cellular bone, and capped with an opistural cartilage that develops from the sheath of the urostylic notochord. A previously undescribed muscle, with its origin on the opistural cartilage, inserts on the lepidotrich ventral to it.
Assuntos
Nadadeiras de Animais/embriologia , Notocorda/embriologia , Salmo salar/embriologia , Crânio/embriologia , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Notocorda/crescimento & desenvolvimento , Salmo salar/crescimento & desenvolvimento , Crânio/crescimento & desenvolvimentoRESUMO
The molecular regulators that determine the precise position of the vertebrate limb along the anterio-posterior axis have not been identified. One model suggests that a combination of hox genes in the lateral plate mesoderm (LPM) promotes formation of the limb field, however redundancy among duplicated paralogs has made this model difficult to confirm. In this study, we identify an optimal window during mid-gastrulation stages when transient mis-regulation of retinoic acid signaling or the caudal related transcription factor, Cdx4, both known regulators of hox genes, can alter the position of the pectoral fin field. We show that increased levels of either RA or Cdx4 during mid-gastrulation are sufficient to rostrally shift the position of the pectoral fin field at the expense of surrounding gene expression in the anterior lateral plate mesoderm (aLPM). Alternatively, embryos deficient for both Cdx4 and Cdx1a (Cdx-deficient) form pectoral fins that are shifted towards the posterior and reveal an additional effect on size of the pectoral fin buds. Prior to formation of the pectoral fin buds, the fin field in Cdx-deficient embryos is visibly expanded into the posterior LPM (pLPM) region at the expense of surrounding gene expression. The effects on gene expression immediately post-gastrulation and during somitogenesis support a model where RA and Cdx4 act in parallel to regulate the position of the pectoral fin. Our transient method is a potentially useful model for studying the mechanisms of limb positioning along the AP axis.
Assuntos
Nadadeiras de Animais/crescimento & desenvolvimento , Gastrulação , Fatores de Transcrição/genética , Tretinoína/fisiologia , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Genes Homeobox , Mesoderma , Peixe-Zebra/genéticaRESUMO
Two main theories have been used to explain the origin of pectoral and pelvic appendages. The "fin-fold theory" proposes that they evolved from a trunk bilateral fin fold, while Gegenbaur's theory assumes they derived from the head branchial arches. However, none of these theories has been fully supported. The "fin-fold" theory is mainly often accepted due to some existing developmental data, but recent developmental studies have revived Gegenbaur's theory by revealing common mechanisms underlying the patterning of branchial arches and paired appendages. Here I review developmental data and many others lines of evidence, which lead to a crucial question: might the apparent contradictions between the two theories be explained by a dual origin of the pectoral appendage, that is, the pectoral girdle and fin/limb being mainly related to the head and trunk, respectively? If this is so then (a) the pectoral and pelvic girdles would not be serial homologues; (b) the term "developmental serial homologues" could only potentially be applied to the pectoral and pelvic fins/limbs. Fascinatingly, in a way this would be similar to what Owen had already suggested, more than 170 years ago: that the pectoral and pelvic girdles are mainly related to the head and trunk, respectively.
Assuntos
Nadadeiras de Animais/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Brânquias/crescimento & desenvolvimento , Animais , Evolução Biológica , Extremidades/fisiologia , Peixes , Fósseis , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Camundongos , Filogenia , UrodelosRESUMO
Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate (Leucoraja erinacea) mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling Sox5/6/9+ perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis.
For our joints to move around freely, they are lubricated with cartilage. In growing mammals, this tissue is continuously made by the body. But, by adulthood, this cartilage will have been almost entirely replaced by bone. It is also difficult for adult bodies to replenish what cartilage does remain such as that in the joints. When growing new cartilage, the body uses so-called progenitor cells, which have the ability to turn into different cell types. Progenitor cells are recruited to the joints, where they transform into cartilage cells called chondrocytes, which generate new cartilage. But adults lack these progenitor cells, leaving them unfit to heal damaged cartilage after injury or diseases like osteoarthritis. In contrast, certain groups of fishes, such as skates, sharks and rays, produce cartilage throughout their life indeed their whole skeleton is made of cartilage. So, what is the difference between these cartilaginous fishes and mammals? Why can they generate cartilage throughout their lives, while humans are unable to? And does this mean that these adult fish are better at healing injured cartilage? Marconi et al. used skates (Leucoraja erinacea) to study how cartilage develops, grows and heals in a cartilaginous fish. Progenitor cells were found in a layer that wraps around the cartilage skeleton (called the perichondrium). These cells were also shown to activate genes that control cartilage development. By labelling these progenitor cells, their presence and movements could be tracked around the fish. Marconi et al. found progenitor cells in adult skates that were able to generate chondrocytes. Skates were also shown to spontaneously repair damaged cartilage in experiments where cartilage was injured. Marconi et al. have identified the skate as a new animal model for studying cartilage growth and repair. Studying the mechanisms that skate progenitor cells use for generating cartilage could lead to improvements in current therapies used for repairing cartilage in the joints.
Assuntos
Cartilagem/fisiologia , Condrogênese , Rajidae/fisiologia , Nadadeiras de Animais/embriologia , Nadadeiras de Animais/crescimento & desenvolvimento , Nadadeiras de Animais/metabolismo , Animais , Cartilagem/embriologia , Cartilagem/crescimento & desenvolvimento , Cartilagem/lesões , Proliferação de Células , Condrócitos/citologia , Condrócitos/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Expressão Gênica , Rajidae/genética , Rajidae/crescimento & desenvolvimento , Células-Tronco/citologia , Células-Tronco/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
As zebrafish develop, black and gold stripes form across their skin due to the interactions of brightly colored pigment cells. These characteristic patterns emerge on the growing fish body, as well as on the anal and caudal fins. While wild-type stripes form parallel to a horizontal marker on the body, patterns on the tailfin gradually extend distally outward. Interestingly, several mutations lead to altered body patterns without affecting fin stripes. Through an exploratory modeling approach, our goal is to help better understand these differences between body and fin patterns. By adapting a prior agent-based model of cell interactions on the fish body, we present an in silico study of stripe development on tailfins. Our main result is a demonstration that two cell types can produce stripes on the caudal fin. We highlight several ways that bone rays, growth, and the body-fin interface may be involved in patterning, and we raise questions for future work related to pattern robustness.
Assuntos
Modelos Biológicos , Peixe-Zebra/crescimento & desenvolvimento , Nadadeiras de Animais/anatomia & histologia , Nadadeiras de Animais/citologia , Nadadeiras de Animais/crescimento & desenvolvimento , Animais , Padronização Corporal/genética , Padronização Corporal/fisiologia , Comunicação Celular/fisiologia , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Simulação por Computador , Epitélio/crescimento & desenvolvimento , Conceitos Matemáticos , Mutação , Pigmentação da Pele/genética , Pigmentação da Pele/fisiologia , Análise de Sistemas , Peixe-Zebra/genética , Peixe-Zebra/fisiologiaRESUMO
Secreted growth factors can act as morphogens that form spatial concentration gradients in developing organs, thereby controlling growth and patterning. For some morphogens, adaptation of the gradients to tissue size allows morphological patterns to remain proportioned as the organs grow. In the zebrafish pectoral fin, we found that BMP signaling forms a two-dimensional gradient. The length of the gradient scales with tissue length and its amplitude increases with fin size according to a power-law. Gradient scaling and amplitude power-laws are signatures of growth control by time derivatives of morphogenetic signaling: cell division correlates with the fold change over time of the cellular signaling levels. We show that Smoc1 regulates BMP gradient scaling and growth in the fin. Smoc1 scales the gradient by means of a feedback loop: Smoc1 is a BMP agonist and BMP signaling represses Smoc1 expression. Our work uncovers a layer of morphogen regulation during vertebrate appendage development.
Assuntos
Nadadeiras de Animais/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Transdução de Sinais , Peixe-Zebra/metabolismo , Nadadeiras de Animais/anatomia & histologia , Nadadeiras de Animais/crescimento & desenvolvimento , Nadadeiras de Animais/ultraestrutura , Animais , Animais Geneticamente Modificados , Anisotropia , Larva/ultraestrutura , Tamanho do Órgão , Fenótipo , Proteínas de Peixe-Zebra/metabolismoRESUMO
The monobasal pectoral fins of living coelacanths and lungfishes are homologous to the forelimbs of tetrapods and are thus critical to investigate the origin thereof. However, it remains unclear whether the similarity in the asymmetrical endoskeletal arrangement of the pectoral fins of coelacanths reflects the evolution of the pectoral appendages in sarcopterygians. Here, we describe for the first time the development of the pectoral fin and shoulder girdle in the extant coelacanth Latimeria chalumnae, based on the tomographic acquisition of a growth series. The pectoral girdle and pectoral fin endoskeleton are formed early in development with a radially outward growth of the endoskeletal elements. The visualization of the pectoral girdle during development shows a reorientation of the girdle between the fetus and pup 1 stages, creating a contact between the scapulocoracoids and the clavicles in the ventro-medial region. Moreover, we observed a splitting of the pre- and post-axial cartilaginous plates in respectively pre-axial radials and accessory elements on one hand, and in post-axial accessory elements on the other hand. However, the mechanisms involved in the splitting of the cartilaginous plates appear different from those involved in the formation of radials in actinopterygians. Our results show a proportional reduction of the proximal pre-axial radial of the fin, rendering the external morphology of the fin more lobe-shaped, and a spatial reorganization of elements resulting from the fragmentation of the two cartilaginous plates. Latimeria development hence supports previous interpretations of the asymmetrical pectoral fin skeleton as being plesiomorphic for coelacanths and sarcopterygians.
Assuntos
Nadadeiras de Animais/crescimento & desenvolvimento , Evolução Biológica , Peixes/crescimento & desenvolvimento , Esqueleto/crescimento & desenvolvimento , Nadadeiras de Animais/anatomia & histologia , Animais , Peixes/anatomia & histologia , Fósseis , Esqueleto/anatomia & histologiaRESUMO
BACKGROUND: Cuban sugarcane wax acids (SCWA) and policosanol (PCO) are mixtures of higher aliphatic acids and alcohols, respectively, purified from sugarcane wax with different chief components. Although it has been known that they have antioxidant and anti-inflammatory activities, physiological properties on molecular mechanism of SCWA have been less studied than PCO. METHODS: In this study, we compared antiatherogenic activities of SCWA and PCO via encapsulation with reconstituted high-density lipoproteins (rHDL). RESULTS: After reconstitution, SCWA-rHDL showed smaller particle size than PCO-rHDL with increase of content. PCO-rHDL or SCWA-rHDL showed distinct inhibition of glycation with similar extent in the presence of fructose. PCO-rHDL or SCWA-rHDL showed strong antioxidant activity against cupric ion-mediated oxidation of low-density lipoproteins (LDL), and inhibition of oxLDL uptake into macrophages. Although PCO-rHDL showed 1.2-fold stronger inhibition against cholesteryl ester transfer protein (CETP) activity than SCWA-rHDL, SCWA-rHDL enhanced 15% more brain cell (BV-2) growth and 23% more regeneration of tail fin in zebrafish. CONCLUSION: PCO and SCWA both enhance the beneficial functions of HDL to maximize its antioxidant, antiglycation, and antiatherosclerotic activities and the inhibition of CETP. These enhancements of HDL functionality by PCO and SCWA could exert antiaging and rejuvenation activity.