Mechanism of pectoral fin outgrowth in zebrafish development

Yano, Tohru; Abe, Gembu; Yokoyama, Hitoshi; Kawakami, Koichi; Tamura, Koji

doi:10.1242/dev.075572

Cited by 66 publications

(67 citation statements)

References 62 publications

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“…Each fin/limb bud possesses an apical ectodermal ridge (AER) and zone of polarizing activity (ZPA) [40], [41], which play important roles in growth and patterning [42]–[44]. The AER, a thickened epithelium that rims the distal ends of the buds, is the source of Fgf signals required for P-D limb outgrowth [45]–[48]. The zebrafish AER expresses 4 fgf genes: fgf4 , fgf8a , fgf16 and fgf24 [49], [50].…”

Section: Resultsmentioning

confidence: 99%

Nipbl and Mediator Cooperatively Regulate Gene Expression to Control Limb Development

et al. 2014

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Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS), the most common “cohesinopathy”. It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb), knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions.

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Section: Resultsmentioning

confidence: 99%

Nipbl and Mediator Cooperatively Regulate Gene Expression to Control Limb Development

et al. 2014

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“…In contrast to the AER in tetrapods, which is maintained during limb bud outgrowth, the AER in fish fin buds differentiates into an extended structure, the apical ectoderm fold (AEF), which lifts off the mesenchyme at an early stage and elongates to give rise to the dermoskeleton (Thorogood, 1991). Studies have shown that the repeated experimental removal of the AEF from zebrafish fin buds results in increased mesenchymal cell proliferation and excessive elongation of the mesenchyme, suggesting that prolonged exposure to AER signals induces distal elongation of mesenchyme and the endoskeleton (Yano et al, 2012). By contrast, overexpression of the distal hoxd13a gene in fin buds reduces the size of the AEF and distal expansion of chondrogenic tissue (Freitas et al, 2012).…”

Section: Molecular Insights Into the Fin-to-limb Transitionmentioning

confidence: 99%

Next generation limb development and evolution: old questions, new perspectives

2015

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The molecular analysis of limb bud development in vertebrates continues to fuel our understanding of the gene regulatory networks that orchestrate the patterning, proliferation and differentiation of embryonic progenitor cells. In recent years, systems biology approaches have moved our understanding of the molecular control of limb organogenesis to the next level by incorporating next generation 'omics' approaches, analyses of chromatin architecture, enhancer-promoter interactions and gene network simulations based on quantitative datasets into experimental analyses. This Review focuses on the insights these studies have given into the gene regulatory networks that govern limb development and into the finto-limb transition and digit reductions that occurred during the evolutionary diversification of tetrapod limbs.

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“…Particularly, the tetrapod Dlx5 / Dlx6 and teleost dlx5a/dlx6a genes are expressed in the apical ectodermal ridge (AER) of the developing limbs in mice [12]–[15] and in the pectoral fin fold (PFF) and median fin fold (MFF) giving rise respectively to paired and unpaired fins in zebrafish [16]–[19]. At early stage of fin morphogenesis, teleosts present an AER structurally homologous to the AER of tetrapods [1], [20]. Later, the AER transitions into an elongated pectoral fin fold [20].…”

Section: Introductionmentioning

confidence: 99%

“…At early stage of fin morphogenesis, teleosts present an AER structurally homologous to the AER of tetrapods [1], [20]. Later, the AER transitions into an elongated pectoral fin fold [20]. AER and fin fold structures have been demonstrated to be essential signaling centers during appendage specification and outgrowth in vertebrates [7], [17], [20]–[22].…”

Section: Introductionmentioning

confidence: 99%

“…Later, the AER transitions into an elongated pectoral fin fold [20]. AER and fin fold structures have been demonstrated to be essential signaling centers during appendage specification and outgrowth in vertebrates [7], [17], [20]–[22]. Despite the fact that tetrapod studies have demonstrated the central role of Dlx5/6 genes in limb formation, the implication of dlx5a/6a genes in teleost fin development has been little analyzed beyond examination of expression patterns.…”

Section: Introductionmentioning

confidence: 99%

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The dlx5a/dlx6a Genes Play Essential Roles in the Early Development of Zebrafish Median Fin and Pectoral Structures

2014

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The Dlx5 and Dlx6 genes encode homeodomain transcription factors essential for the proper development of limbs in mammalian species. However, the role of their teleost counterparts in fin development has received little attention. Here, we show that dlx5a is an early marker of apical ectodermal cells of the pectoral fin buds and of the median fin fold, but also of cleithrum precursor cells during pectoral girdle development. We propose that early median fin fold establishment results from the medial convergence of dlx5a-expressing cells at the lateral edges of the neural keel. Expression analysis also shows involvement of dlx5a during appendage skeletogenesis. Using morpholino-mediated knock down, we demonstrate that disrupted dlx5a/6a function results in pectoral fin agenesis associated with misexpression of bmp4, fgf8a, and1 and msx genes. In contrast, the median fin fold presents defects in mesenchymal cell migration and actinotrichia formation, whereas the initial specification seems to occur normally. Our results demonstrate that the dlx5a/6a genes are essential for the induction of pectoral fin outgrowth, but are not required during median fin fold specification. The dlx5a/6a knock down also causes a failure of cleithrum formation associated with a drastic loss of runx2b and col10a1 expression. The data indicate distinct requirements for dlx5a/6a during median and pectoral fin development suggesting that initiation of unpaired and paired fin formation are not directed through the same molecular mechanisms. Our results refocus arguments on the mechanistic basis of paired appendage genesis during vertebrate evolution.

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Mechanism of pectoral fin outgrowth in zebrafish development

Abstract: . (2010). Loss of fish actinotrichia proteins and the fin-to-limb transition. Nature 466, 234-237.We apologise to the authors and readers for this mistake.

Cited by 66 publications

References 62 publications

Nipbl and Mediator Cooperatively Regulate Gene Expression to Control Limb Development

Nipbl and Mediator Cooperatively Regulate Gene Expression to Control Limb Development

Next generation limb development and evolution: old questions, new perspectives

The dlx5a/dlx6a Genes Play Essential Roles in the Early Development of Zebrafish Median Fin and Pectoral Structures

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