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1.
Patterning of the upper versus lower face involves generating distinct pre-skeletal identities along the dorsoventral (DV) axes of the pharyngeal arches. Whereas previous studies have shown roles for BMPs, Endothelin 1 (Edn1) and Jagged1b-Notch2 in DV patterning of the facial skeleton, how these pathways are integrated to generate different skeletal fates has remained unclear. Here, we show that BMP and Edn1 signaling have distinct roles in development of the ventral and intermediate skeletons, respectively, of the zebrafish face. Using transgenic gain-of-function approaches and cell-autonomy experiments, we find that BMPs strongly promote hand2 and msxe expression in ventral skeletal precursors, while Edn1 promotes the expression of nkx3.2 and three Dlx genes (dlx3b, dlx5a and dlx6a) in intermediate precursors. Furthermore, Edn1 and Jagged1b pattern the intermediate and dorsal facial skeletons in part by inducing the BMP antagonist Gremlin 2 (Grem2), which restricts BMP activity to the ventral-most face. We therefore propose a model in which later cross-inhibitory interactions between BMP and Edn1 signaling, in part mediated by Grem2, separate an initially homogenous ventral region into distinct ventral and intermediate skeletal precursor domains.  相似文献   

2.
Genetic studies in mice and zebrafish have revealed conserved requirements for Endothelin 1 (Edn1) signaling in craniofacial development. Edn1 acts through its cognate type-A receptor (Ednra) to promote ventral skeletal fates and lower-jaw formation. Here, we describe the isolation and characterization of two zebrafish ednra genes - ednra1 and ednra2 - both of which are expressed in skeletal progenitors in the embryonic neural crest. We show that they play partially redundant roles in lower-jaw formation and development of the jaw joint. Knockdown of Ednra1 leads to fusions between upper- and lower-jaw cartilages, whereas the combined loss of Ednra1 and Ednra2 eliminates the lower jaw, similar to edn1-/- mutants. edn1 is expressed in pharyngeal arch ectoderm, mesoderm and endoderm. Tissue-mosaic studies indicate that, among these tissues, a crucial source of Edn1 is the surface ectoderm. This ectoderm also expresses ednrA1 in an edn1-dependent manner, suggesting that edn1 autoregulates its own expression. Collectively, our results indicate that Edn1 from the pharyngeal ectoderm signals through Ednra proteins to direct early dorsoventral patterning of the skeletogenic neural crest.  相似文献   

3.
4.
Albertson RC  Kocher TD 《Heredity》2006,97(3):211-221
Cichlids have undergone extensive evolutionary modifications of their feeding apparatus, making them an ideal model to study the factors that underlie craniofacial diversity. Recent studies have provided critical insights into the molecular mechanisms that have contributed to the origin and maintenance of cichlid trophic diversity. We review this body of work, which shows that the cichlid jaw is regulated by a few genes of major additive effect, and is composed of modules that have evolved under strong divergent selection. Adaptive variation in cichlid jaw shape is evident early in development and is associated with allelic variation in and expression of bmp4. Modulating this growth factor in the experimentally tractable zebrafish model reproduces natural variation in cichlid jaw shape, supporting a role for bmp4 in craniofacial evolution. These data demonstrate the utility of the cichlid jaw as a model for studying the genetic and developmental basis of evolutionary changes in craniofacial morphology.  相似文献   

5.
Morphogenesis of the vertebrate head relies on proper dorsal-ventral (D-V) patterning of neural crest cells (NCC) within the pharyngeal arches. Endothelin-1 (Edn1)-induced signaling through the endothelin-A receptor (Ednra) is crucial for cranial NCC patterning within the mandibular portion of the first pharyngeal arch, from which the lower jaw arises. Deletion of Edn1, Ednra or endothelin-converting enzyme in mice causes perinatal lethality due to severe craniofacial birth defects. These include homeotic transformation of mandibular arch-derived structures into more maxillary-like structures, indicating a loss of NCC identity. All cranial NCCs express Ednra whereas Edn1 expression is limited to the overlying ectoderm, core paraxial mesoderm and pharyngeal pouch endoderm of the mandibular arch as well as more caudal arches. To define the developmental significance of Edn1 from each of these layers, we used Cre/loxP technology to inactivate Edn1 in a tissue-specific manner. We show that deletion of Edn1 in either the mesoderm or endoderm alone does not result in cellular or molecular changes in craniofacial development. However, ectodermal deletion of Edn1 results in craniofacial defects with concomitant changes in the expression of early mandibular arch patterning genes. Importantly, our results also both define for the first time in mice an intermediate mandibular arch domain similar to the one defined in zebrafish and show that this region is most sensitive to loss of Edn1. Together, our results illustrate an integral role for ectoderm-derived Edn1 in early arch morphogenesis, particularly in the intermediate domain.  相似文献   

6.
The morphologies of individual bones are crucial for their functions within the skeleton, and vary markedly during evolution. Recent studies have begun to reveal the detailed molecular genetic pathways that underlie skeletal morphogenesis. On the other hand, understanding of the process of morphogenesis itself has not kept pace with the molecular work. We examined, through an extended period of development in zebrafish, how a prominent craniofacial bone, the opercle (Op), attains its adult morphology. Using high-resolution confocal imaging of the vitally stained Op in live larvae, we show that the bone initially appears as a simple linear spicule, or spur, with a characteristic position and orientation, and lined by osteoblasts that we visualize by transgenic labeling. The Op then undergoes a stereotyped sequence of shape transitions, most notably during the larval period occurring through three weeks postfertilization. New shapes arise, and the bone grows in size, as a consequence of anisotropic addition of new mineralized bone matrix along specific regions of the pre-existing bone surfaces. We find that two modes of matrix addition, spurs and veils, are primarily associated with change in shape, whereas a third mode, incremental banding, largely accounts for growth in size. Furthermore, morphometric analyses show that shape development and growth follow different trajectories, suggesting separate control of bone shape and size. New osteoblast arrangements are associated with new patterns of matrix outgrowth, and we propose that fine developmental regulation of osteoblast position is a critical determinant of the spatiotemporal pattern of morphogenesis.  相似文献   

7.
Our laboratory studies craniofacial skeletal and tooth regeneration. One approach we are using is to exploit the zebrafish model via a large‐scale, forward genetic, chemical N‐ethyl‐nitroso‐urea (ENU) mutagenesis screen to identify genes regulating mineralized craniofacial, axial and dental development. The fact that zebrafish continuously regenerate their teeth makes them an extremely useful model to study tooth regeneration. Our goal is to identify and characterize molecular genetic signaling pathways regulating these processes, which can be manipulated via targeted gene delivery strategies. Through these efforts, we hope to eventually define methods for effective, clinically relevant bone and tooth replacement therapies in humans. Here, we describe our studies using the zebrafish model, which are proving to be useful for the identification and characterization of genes regulating mineralized tissue formation, regeneration, and homeostasis. Although preliminary at the present time, we anticipate the elucidation of novel signaling pathways regulating bone and tooth regeneration, which will eventually facilitate the repair of human skeletal and dental dysplasias.  相似文献   

8.
Protrusile jaws are a highly useful innovation that has been linked to extensive diversification in fish feeding ecology. Jaw protrusion can enhance the performance of multiple functions, such as suction production and capturing elusive prey. Identifying the developmental factors that alter protrusion ability will improve our understanding of fish diversification. In the zebrafish protrusion arises postmetamorphosis. Fish metamorphosis typically includes significant changes in trophic morphology, accompanies a shift in feeding niche and coincides with increased thyroid hormone production. We tested whether thyroid hormone affects the development of zebrafish feeding mechanics. We found that it affected all developmental stages examined, but that effects were most pronounced after metamorphosis. Thyroid hormone levels affected the development of jaw morphology, feeding mechanics, shape variation, and cranial ossification. Adult zebrafish utilize protrusile jaws, but an absence of thyroid hormone impaired development of the premaxillary bone, which is critical to jaw protrusion. Premaxillae from early juvenile zebrafish and hypothyroid adult zebrafish resemble those from adults in the genera Danionella, Devario, and Microdevario that show little to no jaw protrusion. Our findings suggest that evolutionary changes in how the developing skulls of danionin minnows respond to thyroid hormone may have promoted diversification into different feeding niches.  相似文献   

9.
Mechanical forces influence the induction, growth and maintenance of the vertebrate skeleton. Using the zebrafish, Danio rerio, we explore the hypothesis that mechanical forces can ultimately lead to the generation of skeletal evolutionary novelties by modifications of the mechano‐responsive molecular pathways. Locomotion and feeding in zebrafish larvae begin early in ontogeny and it is likely that forces incurred during these behaviours affect subsequent skeletal development. We provide two case studies in which our hypothesis is being tested: the kinethmoid and intermuscular bones. The kinethmoid is a synapomorphy for the order Cypriniformes and is intricately linked to the bones of the protrusible upper jaw. It undergoes chondrogenesis within a ligament well after muscular forces are present within the head. Subsequent ossification of the kinethmoid occurs at sites of ligamentous attachment, leading us to believe that mechanical forces are involved. Unlike the kinethmoid, which has evolved only once, intermuscular bones have evolved several times during teleostean evolution. Intermuscular bones are embedded within the myosepta, the collagenous sheets between axial muscles. The effect of mechanical forces on the development of these intermuscular bones is experimentally tested by increasing the viscosity of the water in which larval zebrafish are raised. Since locomotion in high viscosity requires greater muscular forces, we can directly test the influence of mechanical forces on the development of intermuscular bones. Using developmental techniques paired with outgroup comparison for the kinethmoid, and direct experimentation for intermuscular bones, our case studies provide complementary insights into the effects of mechanical forces on the evolution of skeletal novelties in fishes.  相似文献   

10.
Bone morphogenetic proteins (BMPs) play crucial roles in craniofacial development but little is known about their interactions with other signals, such as Endothelin 1 (Edn1) and Jagged/Notch, which pattern the dorsal-ventral (DV) axis of the pharyngeal arches. Here, we use transgenic zebrafish to monitor and perturb BMP signaling during arch formation. With a BMP-responsive transgene, Tg(Bre:GFP), we show active BMP signaling in neural crest (NC)-derived skeletal precursors of the ventral arches, and in surrounding epithelia. Loss-of-function studies using a heat shock-inducible, dominant-negative BMP receptor 1a [Tg(hs70I:dnBmpr1a-GFP)] to bypass early roles show that BMP signaling is required for ventral arch development just after NC migration, the same stages at which we detect Tg(Bre:GFP). Inhibition of BMP signaling at these stages reduces expression of the ventral signal Edn1, as well as ventral-specific genes such as hand2 and dlx6a in the arches, and expands expression of the dorsal signal jag1b. This results in a loss or reduction of ventral and intermediate skeletal elements and a mis-shapen dorsal arch skeleton. Conversely, ectopic BMP causes dorsal expansion of ventral-specific gene expression and corresponding reductions/transformations of dorsal cartilages. Soon after NC migration, BMP is required to induce Edn1 and overexpression of either signal partially rescues ventral skeletal defects in embryos deficient for the other. However, once arch primordia are established the effects of BMPs become restricted to more ventral and anterior (palate) domains, which do not depend on Edn1. This suggests that BMPs act upstream and in parallel to Edn1 to promote ventral fates in the arches during early DV patterning, but later acquire distinct roles that further subdivide the identities of NC cells to pattern the craniofacial skeleton.  相似文献   

11.
12.
Lesions in the epithelially expressed human gene FRAS1 cause Fraser syndrome, a complex disease with variable symptoms, including facial deformities and conductive hearing loss. The developmental basis of facial defects in Fraser syndrome has not been elucidated. Here we show that zebrafish fras1 mutants exhibit defects in facial epithelia and facial skeleton. Specifically, fras1 mutants fail to generate a late-forming portion of pharyngeal pouch 1 (termed late-p1) and skeletal elements adjacent to late-p1 are disrupted. Transplantation studies indicate that fras1 acts in endoderm to ensure normal morphology of both skeleton and endoderm, consistent with well-established epithelial expression of fras1. Late-p1 formation is concurrent with facial skeletal morphogenesis, and some skeletal defects in fras1 mutants arise during late-p1 morphogenesis, indicating a temporal connection between late-p1 and skeletal morphogenesis. Furthermore, fras1 mutants often show prominent second arch skeletal fusions through space occupied by late-p1 in wild type. Whereas every fras1 mutant shows defects in late-p1 formation, skeletal defects are less penetrant and often vary in severity, even between the left and right sides of the same individual. We interpret the fluctuating asymmetry in fras1 mutant skeleton and the changes in fras1 mutant skeletal defects through time as indicators that skeletal formation is destabilized. We propose a model wherein fras1 prompts late-p1 formation and thereby stabilizes skeletal formation during zebrafish facial development. Similar mechanisms of stochastic developmental instability might also account for the high phenotypic variation observed in human FRAS1 patients.  相似文献   

13.
? Inflorescence architecture is important to angiosperm reproduction, but our knowledge of the developmental basis underlying the evolution of inflorescence architectures is limited. Using a phylogeny-based comparative analysis of developmental pathways, we tested the long-standing hypothesis that umbel evolved from elongated inflorescences by suppression of inflorescence branches, while head evolved from umbels by suppression of pedicels. ? The developmental pathways of six species of Cornus producing different inflorescence types were characterized by scanning electron microscopy (SEM) and histological analysis. Critical developmental events were traced over the molecular phylogeny to identify evolutionary changes leading to the formation of umbels and heads using methods accounting for evolutionary time and phylogenetic uncertainty. ? We defined 24 developmental events describing the developmental progression of the different inflorescence types. The evolutionary transition from paniculate cymes to umbels and heads required alterations of seven developmental events occurring at different evolutionary times. ? Our results indicate that heads and umbels evolved independently in Cornus from elongated forms via an umbellate dichasium ancestor and this process involved several independent changes. Our findings shed novel insights into head and umbel evolution concealed by outer morphology. Our work illustrates the importance of combining developmental and phylogenetic data to better define morphological evolutionary processes.  相似文献   

14.
Johnson  Norman A.  Porter  Adam H. 《Genetica》2001,(1):45-58
Despite the recent synthesis of developmental genetics and evolutionary biology, current theories of adaptation are still strictly phenomenological and do not yet consider the implications of how phenotypes are constructed from genotypes. Given the ubiquity of regulatory genetic pathways in developmental processes, we contend that study of the population genetics of these pathways should become a major research program. We discuss the role divergence in regulatory developmental genetic pathways may play in speciation, focusing on our theoretical and computational investigations. We also discuss the population genetics of molecular co-option, arguing that mutations of large effect are not needed for co-option. We offer a prospectus for future research, arguing for a new synthesis of the population genetics of development.  相似文献   

15.
Reversing opinions on Dollo's Law   总被引:1,自引:0,他引:1  
Dollo's Law, the idea that the loss of complex features in evolution is irreversible, is a popular concept in evolutionary biology. Here we review how application of recent phylogenetic methods, genomics and evo-devo approaches is changing our view of Dollo's Law and its underlying mechanisms. Phylogenetic studies have recently demonstrated cases where seemingly complex features such as digits and wings have been reacquired. Meanwhile, large genomics databases and evo-devo studies are showing how the underlying developmental pathways and genetic architecture can be retained after the loss of a character. With dwindling evidence for the law-like nature of Dollo's Law, we anticipate a return to Dollo's original focus on irreversibility of all kinds of changes, not exclusively losses.  相似文献   

16.
Molecular genetic analysis of phenotypic variation has revealed many examples of evolutionary change in the developmental pathways that control plant and animal morphology. A major challenge is to integrate the information from diverse organisms and traits to understand the general patterns of developmental evolution. This integration can be facilitated by evolutionary metamodels—traits that have undergone multiple independent changes in different species and whose development is controlled by well-studied regulatory pathways. The metamodel approach provides the comparative equivalent of experimental replication, allowing us to test whether the evolution of each developmental pathway follows a consistent pattern, and whether different pathways are predisposed to different modes of evolution by their intrinsic organization. A review of several metamodels suggests that the structure of developmental pathways may bias the genetic basis of phenotypic evolution, and highlights phylogenetic replication as a value-added approach that produces deeper insights into the mechanisms of evolution than single-species analyses.  相似文献   

17.
This article introduces a special issue on zebrafish biology that attempts to integrate developmental genetics with comparative studies of other fish species. For zebrafish researchers, comparative work offers a better understanding of the evolutionary history of their model system. Comparative biologists can gain many insights from the developmental and genetic mechanisms revealed in zebrafish that have contributed to the huge range of morphological variation among fishes that has arisen over millions of years. These ideas are considered here in various contexts, including systematics, genome organization and the development of the nervous system, pigmentation, craniofacial skeleton and dentition. Studies of the zebrafish in phylogenetic context provide an opportunity for synergy between communities using these two fundamentally different approaches.  相似文献   

18.
Convergent extension driven by mediolateral intercalation of chondrocytes is a key process that contributes to skeletal growth and morphogenesis. While progress has been made in deciphering the molecular mechanism that underlies this process, the involvement of mechanical load exerted by muscle contraction in its regulation has not been studied. Using the zebrafish as a model system, we found abnormal pharyngeal cartilage morphology in both chemically and genetically paralyzed embryos, demonstrating the importance of muscle contraction for zebrafish skeletal development. The shortening of skeletal elements was accompanied by prominent changes in cell morphology and organization. While in control the cells were elongated, chondrocytes in paralyzed zebrafish were smaller and exhibited a more rounded shape, confirmed by a reduction in their length-to-width ratio. The typical columnar organization of cells was affected too, as chondrocytes in various skeletal elements exhibited abnormal stacking patterns, indicating aberrant intercalation. Finally, we demonstrate impaired chondrocyte intercalation in growth plates of muscle-less Sp(d) mouse embryos, implying the evolutionary conservation of muscle force regulation of this essential morphogenetic process.Our findings provide a new perspective on the regulatory interaction between muscle contraction and skeletal morphogenesis by uncovering the role of muscle-induced mechanical loads in regulating chondrocyte intercalation in two different vertebrate models.  相似文献   

19.
The morphogenesis of the vertebrate skull results from highly dynamic integrated processes involving the exchange of signals between the ectoderm, the endoderm, and cephalic neural crest cells (CNCCs). Before migration CNCCs are not committed to form any specific skull element, molecular signals exchanged in restricted regions of tissue interaction are crucial in providing positional identity to the CNCCs mesenchyme and activate the specific morphogenetic process of different skeletal components of the head. In particular, the endothelin‐1 (Edn1)‐dependent activation of Dlx5 and Dlx6 in CNCCs that colonize the first pharyngeal arch (PA1) is necessary and sufficient to specify maxillo‐mandibular identity. Here, to better analyze the spatio‐temporal dynamics of this process, we associate quantitative gene expression analysis with detailed examination of skeletal phenotypes resulting from combined allelic reduction of Edn1, Dlx5, and Dlx6. We show that Edn1‐dependent and ‐independent regulatory pathways act at different developmental times in distinct regions of PA1. The Edn1→Dlx5/6→Hand2 pathway is already active at E9.5 during early stages of CNCCs colonization. At later stages (E10.5) the scenario is more complex: we propose a model in which PA1 is subdivided into four adjacent territories in which distinct regulations are taking place. This new developmental model may provide a conceptual framework to interpret the craniofacial malformations present in several mouse mutants and in human first arch syndromes. More in general, our findings emphasize the importance of quantitative gene expression in the fine control of morphogenetic events. genesis 48:362–373, 2010. © 2010 Wiley‐Liss, Inc.  相似文献   

20.
Over the past two to three decades, developmental biology has demonstrated that all multicellular organisms in the animal kingdom share many of the same molecular building blocks and many of the same regulatory genetic pathways. Yet we still do not understand how the various organisms use these molecules and pathways to assume all the forms we know today. Evolutionary developmental biology tackles this problem by comparing the development of one organism to another and comparing the genes involved and gene functions to understand what makes one organism different from another. In this review, we revisit a set of seven concepts defined by Lewis Wolpert (fate maps, asymmetric division, induction, competence, positional information, determination, and lateral inhibition) that describe the characters of many developmental systems and supplement them with three additional concepts (developmental genomics, genetic redundancy, and genetic networks). We will discuss examples of comparative developmental studies where these concepts have guided observations on the advent of a developmental novelty. Finally, we identify a set of evolutionary frameworks, such as developmental constraints, cooption, duplication, parallel and convergent evolution, and homoplasy, to adequately describe the evolutionary properties of developmental systems.  相似文献   

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