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Similarities and differences in the regulation of HoxD genes during chick and mouse limb development [4C-seq]

ABSTRACT: Hoxd genes are important for limb development in all tetrapods examined thus far. In mouse, they are controlled by a complex bimodal regulation, which regulates first the proximal patterning, then the distal structure, allowing at the same time the formation of the wrist and ankle articulations. We analyzed the existence of this regulatory mechanism in chicken, i.e. in an animal where large morphological differences exist between fore- and hindlimbs. We report that while this bimodal regulation is globally conserved between mammals and avian, some important modifications evolved at least between these two model systems, in particular regarding the activity of specific enhancer and the position of the TAD boundary and the forelimb versus hindlimb comparative regulations. Some aspects of these regulations seem to be more conserved between chick and bats than with the mouse situation, which may relate to the extent to which forelimbs and hindlimbs of these various animals differ in their functions.

ORGANISM(S): Mus musculus Gallus gallus

PROVIDER: GSE115560 | GEO | 2018/11/27

REPOSITORIES: GEO

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Project description:Hoxd genes are important for limb development in all tetrapods examined thus far. In mouse, they are controlled by a complex bimodal regulation, which regulates first the proximal patterning, then the distal structure, allowing at the same time the formation of the wrist and ankle articulations. We analyzed the existence of this regulatory mechanism in chicken, i.e. in an animal where large morphological differences exist between fore- and hindlimbs. We report that while this bimodal regulation is globally conserved between mammals and avian, some important modifications evolved at least between these two model systems, in particular regarding the activity of specific enhancer and the position of the TAD boundary and the forelimb versus hindlimb comparative regulations. Some aspects of these regulations seem to be more conserved between chick and bats than with the mouse situation, which may relate to the extent to which forelimbs and hindlimbs of these various animals differ in their functions.

2018-11-27 | GSE115559 | GEO

2018-11-27 | GSE115562 | GEO

2018-11-27 | GSE115561 | GEO

Digital gene expression tag profiling of digit morphologies in bats

Project description:As the only truly flying mammals, bats use their unique wing formed from elongated digits connected by membranes to power their flight. The forelimb of bats consists of four elongated digits (digits II-V) and one shorter digit (digit I) that is morphologically similar to the hindlimb digits. Elongation of bat forelimb digits is thought to results from changes in the temporal and spatial expression of a number of developmental genes. As a result, comparing gene expression profiles between short and elongated digit morphologies of the fore- and hindlimbs may elucidate the molecular mechanisms underlying digit elongation in bats. Here, we performed a large-scale analysis of gene expression of forelimb digit I, forelimb digits II-V, and all five hindlimb digits in Myotis ricketti using digital gene expression tag profiling approach. Results of this study not only implicate several developmental genes as robust candidates underlying digit elongation in bats, but also provide a better understanding of the genes involved in autopodial development in general. A large-scale analysis of gene expression of 3 different parts of autopods in Myotis ricketti using digital gene expression tag profiling approach.

2010-12-06 | E-GEOD-20038 | biostudies-arrayexpress

Digital gene expression tag profiling of digit morphologies in bats

2010-12-06 | GSE20038 | GEO

ATAC-seq analysis to examine global accessibilty of chromatin in limb bud cells

Project description:The study compares two cell populations one where Etv2 is expressed and other lacks Etv2 expression. The cells from wild-type E9.5 hindlimbs , cells from Shh-EGFP E10.5 anterior hindlimbs , EGFP+ cells from Shh-EGFP E10.5 posterior hindlimbs, and EYFP+ cells from Etv2-EYFP transgenic E10.5 hindlimbs and forelimbs were collected and processed

2022-06-28 | GSE192865 | GEO

Transcriptome comparison of bat (Miniopterus natalensis) forelimb and hindlimb autopods at developmental stages CS16 and CS17 and E13.5 mouse forelimb autopods

Project description:The bat offers an alternative paradigm to the standard mouse and chick model of limb development as it has extremely divergent forelimbs (long digits supporting a wing) and hindlimbs (short digits and claws) due the distinct requirements of both aerial and terrestrial locomotion. We used a cross-species microarray approach to identify differentially expressed (DE) genes between the bat (Minniopterus natalensis) forelimb and hindlimb autopods at Carollia developmental stages (CS) 16 and CS17, and between the bat (CS17) and mouse (E13.5) forelimb autopods. Several DE genes were identified, including two homeobox genes, Meis2, a proximal limb-patterning gene, and Hoxd11, a gene involved in digit elongation. Both genes are significantly over-expressed in the developing bat forelimb as compared to the hindlimb and equivalently staged mouse forelimbs. A reference design was used in this microarray experiment. A pool of left and right mouse forelimb autopods from 24 embryos was used as the reference sample. This sample was directly compared to individual CS16 and CS17 bat fore- and hindlimbs (left and right of one individual pooled) that were classified as the test conditions. Four experimental sessions were performed using an independently amplified mouse reference pool and 4 biological repeats for the bat limbs. These samples were co-hybridised to OPERON Mouse OpArray (ver. 4.0) spotted oligonucleotide slides to perform a competitive Cross-Species Hybridisation experiment. The bat aRNA (test) samples were labelled with Cy3 dye (green signal), the mouse aRNA (reference) sample was labelled with Cy5 dye (red signal).

2014-02-15 | E-GEOD-51042 | biostudies-arrayexpress

Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis

Project description:The regulatory specificity of enhancers and their interaction with gene promoters is thought to be controlled by their sequence and the binding of transcription factors. By studying Pitx1, a regulator of hindlimb development, we show that dynamic changes in chromatin conformation can restrict the activity of enhancers. Inconsistent with its hindlimb-restricted expression, Pitx1 is controlled by an enhancer (Pen) that shows activity in forelimbs and hindlimbs. By Capture Hi-C and three-dimensional modeling of the locus, we demonstrate that forelimbs and hindlimbs have fundamentally different chromatin configurations, whereby Pen and Pitx1 interact in hindlimbs and are physically separated in forelimbs. Structural variants can convert the inactive into the active conformation, thereby inducing Pitx1 misexpression in forelimbs, causing partial arm-to-leg transformation in mice and humans. Thus, tissue-specific three-dimensional chromatin conformation can contribute to enhancer activity and specificity in vivo and its disturbance can result in gene misexpression and disease.

2018-10-01 | GSE103676 | GEO

Conservation and divergence of regulatory strategies and the origin of tetrapod digits

Project description:The evolution of tetrapod limbs from fish fins enabled the conquest of land by vertebrates and thus represents a key step in evolution. Despite the use of comparative gene expression analyses, critical aspects of this transformation remain controversial, in particularly the origin of digits. Hoxa and Hoxd genes are essential for the specification of the different limb segments and their functional abrogation leads to large truncations of the appendages. Here we show that the selective transcription of mouse Hoxa genes in proximal and distal limbs is related to a bimodal higher order chromatin structure, similar to that reported for Hoxd genes, thus revealing a generic regulatory strategy implemented by both gene clusters during limb development. We found the same bimodal chromatin architecture in fish embryos, indicating that the regulatory strategy used to pattern tetrapod limbs predates the divergence between fish and tetrapods. However, when assessed in mice, both fish regulatory domains triggered transcription in proximal, rather than distal limb territories, supporting an evolutionary scenario whereby digits arose as true tetrapod novelties through genetic retrofitting of a preexisting bimodal chromatin framework. We discuss the possibility to consider regulatory circuitries, rather than expression patterns, as essential parameters to define evolutionary synapomorphies. Circular Chromosome Conformation Capture (4C seq) at the mouse HoxA and HoxD loci in proximal and distal forelimbs and forebrain at E12.5 and at the zebrafish HoxAa, HoxAb and HoxDa loci in 5 dpf whole embryos.

2014-01-21 | E-GEOD-47644 | biostudies-arrayexpress

Pitx1 directly controls the core limb development program to implement hindlimb identity [ChIP-Seq]

Project description:Pitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology.

2017-09-19 | GSE100728 | GEO

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