Jaw and branchial arch mutants in zebrafish II: anterior arches and cartilage differentiation

Max-Planck-Institut für Entwicklungsbiologie, Abteilung Genetik, Tübingen, Germany.
Development (Impact Factor: 6.46). 01/1997; 123:345-56.
Source: PubMed


In a large scale screen for mutants that affect the early development of the zebrafish, 109 mutants were found that cause defects in the formation of the jaw and the more posterior pharyngeal arches. Here we present the phenotypic description and results of the complementation analysis of mutants belonging to two major classes: (1) mutants with defects in the mandibular and hyoid arches and (2) mutants with defects in cartilage differentiation and growth in all arches. Mutations in four of the genes identified during the screen show specific defects in the first two arches and leave the more posterior pharyngeal arches largely unaffected (schmerle, sucker, hoover and sturgeon). In these mutants ventral components of the mandibular and hyoid arches are reduced (Meckel's cartilage and ceratohyal cartilage) whereas dorsal structures (palatoquadrate and hyosymplectic cartilages) are of normal size or enlarged. Thus, mutations in single genes cause defects in the formation of first and second arch structures but also differentially affect development of the dorsal and ventral structures within one arch. In 27 mutants that define at least 8 genes, the differentiation of cartilage and growth is affected. In hammerhead mutants particularly the mesodermally derived cartilages are reduced, whereas jellyfish mutant larvae are characterized by a severe reduction of all cartilaginous elements, leaving only two pieces in the position of the ceratohyal cartilages. In all other mutant larvae all skeletal elements are present, but consist of smaller and disorganized chondrocytes. These mutants also exhibit shortened heads and reduced pectoral fins. In homozygous knorrig embryos, tumor-like outgrowths of chondrocytes occur along the edges of all cartilaginous elements. The mutants presented here may be valuable tools for elucidating the genetic mechanisms that underlie the development of the mandibular and the hyoid arches, as well as the process of cartilage differentiation.

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    • "These screens were focused on overall embryonic morphology, with mutants affecting craniofacial morphology and the craniofacial skeleton being one class of interest. Several mutations were identified that produced craniofacial malformations including within edn1 (sucker), tfap2a (lockjaw/mont blanc) and tbx1 (van gogh) (Barrallo-Gimeno et al., 2004;Knight et al., 2003;Miller et al., 2000;Piotrowski et al., 2003Piotrowski et al., , 1996Schilling et al., 1996). Additionally, mutations were identified which gave NC specific phenotypes, including within foxd3 (mother superior) (MonteroBalaguer et al., 2006;Neuhauss et al., 1996). "
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    ABSTRACT: The craniofacial skeletal structures that comprise the human head develop from multiple tissues that converge to form the bones and cartilage of the face. Because of their complex development and morphogenesis, many human birth defects arise due to disruptions in these cellular populations. Thus, determining how these structures normally develop is vital if we are to gain a deeper understanding of craniofacial birth defects and devise treatment and prevention options. In this review, we will focus on how animal model systems have been used historically and in an ongoing context to enhance our understanding of human craniofacial development. We do this by first highlighting “animal to man” approaches: that is, how animal models are being utilized to understand fundamental mechanisms of craniofacial development. We discuss emerging technologies, including high throughput sequencing and genome editing, and new animal repository resources, and how their application can revolutionize the future of animal models in craniofacial research. Secondly, we highlight “man to animal” approaches, including the current use of animal models to test the function of candidate human disease variants. Specifically, we outline a common workflow deployed after discovery of a potentially disease causing variant based on a select set of recent examples in which human mutations are investigated in vivo using animal models. Collectively, these topics will provide a pipeline for the use of animal models in understanding human craniofacial development and disease for clinical geneticist and basic researchers alike.
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    • "We next performed mcc loss-of-function studies using two antisense morpholino (MO) oligonucleotides: one targeting the mcc ATG (MO1) and the other spanning the splice junction between intron 6 and exon 7 (MO2) (see Fig. 1A). Embryos injected with either MO display varying degrees of microcephaly/microphthalmia, often with a shift in head position and loss of tissue anterior to the eyes – a 'hammerhead' phenotype (Piotrowski et al., 1996) – tightly packed somites and an embryonic axis that is shorter and ventrally curved from anterior to posterior compared with wild-type controls at 1 day post fertilization (dpf) (Fig. 2A; supplementary material Fig. S2A). "
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    • "The mechanisms involved in skeletal development are highly conserved between zebrafish and the mammalian species, such as the expression and regulation of the major signaling transduction pathways involved in bone development [13] [14] [15]. In the past, a number of mutations that affect zebrafish bone development have been identified [16] [17]. Some of them are highly conserved in vertebrate species (sequence, expression profiles and function). "
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