Hoxd13 Contribution to the Evolution of Vertebrate Appendages

Freitas, Renata; Gómez-Marín, Carlos; Wilson, Jonathan M.; Casares, Fernando; Gómez-Skármeta, José Luis

doi:10.1016/j.devcel.2012.10.015

Cited by 88 publications

(111 citation statements)

References 54 publications

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“…Further, ectopic expression of Hoxd13a in the distal fin enhances proliferation, distal expansion of chondrogenesis and reduction in fin-folding [50]. These findings support the idea that additional cis-regulatory elements in the tetrapod lineage, perhaps including the tetrapod-specific CsC, served to modify a preexisting and conserved gene regulatory network in the distal fin/limb bud.…”

Section: Origin Of the Tetrapod Autopodsupporting

confidence: 72%

The origins, scaling and loss of tetrapod digits

Saxena

Towers

Cooper

2017

Phil. Trans. R. Soc. B

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One contribution of 17 to a theme issue 'Evodevo in the genomics era, and the origins of morphological diversity'. Many of the great morphologists of the nineteenth century marvelled at similarities between the limbs of diverse species, and Charles Darwin noted these homologies as significant supporting evidence for descent with modification from a common ancestor. Sir Richard Owen also took great care to highlight each of the elements of the forelimb and hindlimb in a multitude of species with focused attention on the homology between the hoof of the horse and the middle digit of man. The ensuing decades brought about a convergence of palaeontology, experimental embryology and molecular biology to lend further support to the homologies of tetrapod limbs and their developmental origins. However, for all that we now understand about the conserved mechanisms of limb development and the development of gross morphological disturbances, little of what is presented in the experimental or medical literature reflects the remarkable diversity resulting from the 450 million year experiment of natural selection. An understanding of conserved and divergent limb morphologies in this new age of genomics and genome engineering promises to reveal more of the developmental potential residing in all limbs and to unravel the mechanisms of evolutionary variation in limb size and shape. In this review, we present the current state of our rapidly advancing understanding of the evolutionary origin of hands and feet and highlight what is known about the mechanisms that shape diverse limbs.This article is part of the themed issue 'Evo-devo in the genomics era, and the origins of morphological diversity'.

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Section: Origin Of the Tetrapod Autopodsupporting

confidence: 72%

The origins, scaling and loss of tetrapod digits

Saxena

Towers

Cooper

2017

Phil. Trans. R. Soc. B

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“…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). Two rows of rigid fibrils called actinotrichia keep the AEF straight, and the knockdown of two genes essential for their formation, actinodin1 and -2 (and1/2), results in a defective AEF (Zhang et al, 2010a).…”

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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“…This step, along with the repression of Hoxa11 by Hoxa13, leads to the two-phase, bimodal regulation described at the HoxD locus (Sheth et al 2014;Woltering et al 2014). Such a bimodal regulation allowed the self-enhanced transcription of Hoxd13, which, like Hoxa13, has the ability to stimulate growth and produce cartilage models and long bones of reduced size (Yokouchi et al 1995a;Freitas et al 2012), leading to digits. This also provided the mechanistic opportunity to offset the two domains of transcription and, as a consequence, produce the mesopodial articulation (Villavicencio-Lorini et al 2010;Woltering and Duboule 2010;Andrey et al 2013).…”

Section: Evolution Of Hox Regulation In the Transformation Of Paired mentioning

confidence: 99%

A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus

et al. 2016

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During vertebrate limb development, Hoxd genes are regulated following a bimodal strategy involving two topologically associating domains (TADs) located on either side of the gene cluster. These regulatory landscapes alternatively control different subsets of Hoxd targets, first into the arm and subsequently into the digits. We studied the transition between these two global regulations, a switch that correlates with the positioning of the wrist, which articulates these two main limb segments. We show that the HOX13 proteins themselves help switch off the telomeric TAD, likely through a global repressive mechanism. At the same time, they directly interact with distal enhancers to sustain the activity of the centromeric TAD, thus explaining both the sequential and exclusive operating processes of these two regulatory domains. We propose a model in which the activation of Hox13 gene expression in distal limb cells both interrupts the proximal Hox gene regulation and re-enforces the distal regulation. In the absence of HOX13 proteins, a proximal limb structure grows without any sign of wrist articulation, likely related to an ancestral fish-like condition.

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Hoxd13 Contribution to the Evolution of Vertebrate Appendages

Cited by 88 publications

References 54 publications

The origins, scaling and loss of tetrapod digits

The origins, scaling and loss of tetrapod digits

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

A role for HOX13 proteins in the regulatory switch between TADs at the HoxD locus

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