Publications by authors named "Marie Claire Delfini"

13 Publications

  • Page 1 of 1

Unexpected contribution of fibroblasts to muscle lineage as a mechanism for limb muscle patterning.

Nat Commun 2021 06 22;12(1):3851. Epub 2021 Jun 22.

Developmental Biology Laboratory, Institut Biologie Paris Seine, Sorbonne Université, CNRS, IBPS-UMR 7622, Paris, France.

Positional information driving limb muscle patterning is contained in connective tissue fibroblasts but not in myogenic cells. Limb muscles originate from somites, while connective tissues originate from lateral plate mesoderm. With cell and genetic lineage tracing we challenge this model and identify an unexpected contribution of lateral plate-derived fibroblasts to the myogenic lineage, preferentially at the myotendinous junction. Analysis of single-cell RNA-sequencing data from whole limbs at successive developmental stages identifies a population displaying a dual muscle and connective tissue signature. BMP signalling is active in this dual population and at the tendon/muscle interface. In vivo and in vitro gain- and loss-of-function experiments show that BMP signalling regulates a fibroblast-to-myoblast conversion. These results suggest a scenario in which BMP signalling converts a subset of lateral plate mesoderm-derived cells to a myogenic fate in order to create a boundary of fibroblast-derived myonuclei at the myotendinous junction that controls limb muscle patterning.
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http://dx.doi.org/10.1038/s41467-021-24157-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219714PMC
June 2021

HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of .

Development 2021 02 18;148(4). Epub 2021 Feb 18.

Aix Marseille University, CNRS, IBDM, 13288 Marseille, France

Differential Hox gene expression is central for specification of axial neuronal diversity in the spinal cord. Here, we uncover an additional function of Hox proteins in the developing spinal cord, restricted to B cluster Hox genes. We found that members of the HoxB cluster are expressed in the trunk neural tube of chicken embryo earlier than Hox from the other clusters, with poor antero-posterior axial specificity and with overlapping expression in the intermediate zone (IZ). Gain-of-function experiments of HoxB4, HoxB8 and HoxB9, respectively, representative of anterior, central and posterior HoxB genes, resulted in ectopic progenitor cells in the mantle zone. The search for HoxB8 downstream targets in the early neural tube identified the leucine zipper tumor suppressor 1 gene (), the expression of which is also activated by HoxB4 and HoxB9. Gain- and loss-of-function experiments showed that Lzts1, which is expressed endogenously in the IZ, controls neuronal delamination. These data collectively indicate that HoxB genes have a generic function in the developing spinal cord, controlling the expression of and neuronal delamination.
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http://dx.doi.org/10.1242/dev.195404DOI Listing
February 2021

The Generic Facet of Hox Protein Function.

Trends Genet 2018 12 18;34(12):941-953. Epub 2018 Sep 18.

Aix Marseille Univ, CNRS, IBDM, Marseille, France; http://www.ibdm.univ-mrs.fr/equipe/mechanisms-of-gene-regulation-by-transcription-factors/. Electronic address:

Hox transcription factors are essential to promote morphological diversification of the animal body. A substantial number of studies have focused on how Hox proteins reach functional specificity, an issue that arises from the fact that these transcription factors control distinct developmental functions despite sharing similar molecular properties. In this review, we highlight that, besides specific functions, for which these transcription factors are renowned, Hox proteins also often have nonspecific functions. We next discuss some emerging principles of these generic functions and how they relate to specific functions and explore our current grasp of the underlying molecular mechanisms.
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http://dx.doi.org/10.1016/j.tig.2018.08.006DOI Listing
December 2018

The Hox proteins Ubx and AbdA collaborate with the transcription pausing factor M1BP to regulate gene transcription.

EMBO J 2017 10 4;36(19):2887-2906. Epub 2017 Sep 4.

Aix Marseille Université, CNRS, IBDM, UMR 7288, Marseille, France

In metazoans, the pausing of RNA polymerase II at the promoter (paused Pol II) has emerged as a widespread and conserved mechanism in the regulation of gene transcription. While critical in recruiting Pol II to the promoter, the role transcription factors play in transitioning paused Pol II into productive Pol II is, however, little known. By studying how Hox transcription factors control transcription, we uncovered a molecular mechanism that increases productive transcription. We found that the Hox proteins AbdA and Ubx target gene promoters previously bound by the transcription pausing factor M1BP, containing paused Pol II and enriched with promoter-proximal Polycomb Group (PcG) proteins, yet lacking the classical H3K27me3 PcG signature. We found that AbdA binding to M1BP-regulated genes results in reduction in PcG binding, the release of paused Pol II, increases in promoter H3K4me3 histone marks and increased gene transcription. Linking transcription factors, PcG proteins and paused Pol II states, these data identify a two-step mechanism of Hox-driven transcription, with M1BP binding leading to Pol II recruitment followed by AbdA targeting, which results in a change in the chromatin landscape and enhanced transcription.
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http://dx.doi.org/10.15252/embj.201695751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623858PMC
October 2017

Hox Service Warranty Extends to Adult Bone Repair.

Dev Cell 2016 12;39(6):627-629

Aix-Marseille Université, CNRS, IBDM, UMR7288, case 907, 13288 Marseille Cedex 09, France. Electronic address:

Hox genes are key developmental regulators. In this issue of Developmental Cell, Rux et al. (2016) uncover an adult role for Hox11 genes in regionalized bone repair. This function relies on Hox activity in bone marrow multipotent mesenchymal stem progenitor cells, which promotes skeletal cell differentiation.
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http://dx.doi.org/10.1016/j.devcel.2016.12.007DOI Listing
December 2016

TAFA4, a chemokine-like protein, modulates injury-induced mechanical and chemical pain hypersensitivity in mice.

Cell Rep 2013 Oct 17;5(2):378-88. Epub 2013 Oct 17.

Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.

C-low-threshold mechanoreceptors (C-LTMRs) are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.
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http://dx.doi.org/10.1016/j.celrep.2013.09.013DOI Listing
October 2013

Hox proteins display a common and ancestral ability to diversify their interaction mode with the PBC class cofactors.

PLoS Biol 2012 26;10(6):e1001351. Epub 2012 Jun 26.

Institut de Biologie du Développement de Marseille Luminy, IBDML, UMR7288, CNRS, AMU, Parc Scientifique de Luminy, Case 907, Marseille, France.

Hox transcription factors control a number of developmental processes with the help of the PBC class proteins. In vitro analyses have established that the formation of Hox/PBC complexes relies on a short conserved Hox protein motif called the hexapeptide (HX). This paradigm is at the basis of the vast majority of experimental approaches dedicated to the study of Hox protein function. Here we questioned the unique and general use of the HX for PBC recruitment by using the Bimolecular Fluorescence Complementation (BiFC) assay. This method allows analyzing Hox-PBC interactions in vivo and at a genome-wide scale. We found that the HX is dispensable for PBC recruitment in the majority of investigated Drosophila and mouse Hox proteins. We showed that HX-independent interaction modes are uncovered by the presence of Meis class cofactors, a property which was also observed with Hox proteins of the cnidarian sea anemone Nematostella vectensis. Finally, we revealed that paralog-specific motifs convey major PBC-recruiting functions in Drosophila Hox proteins. Altogether, our results highlight that flexibility in Hox-PBC interactions is an ancestral and evolutionary conserved character, which has strong implications for the understanding of Hox protein functions during normal development and pathologic processes.
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http://dx.doi.org/10.1371/journal.pbio.1001351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383740PMC
October 2012

Stable, conditional, and muscle-fiber-specific expression of electroporated transgenes in chick limb muscle cells.

Dev Dyn 2011 May 2;240(5):1223-32. Epub 2010 Dec 2.

CNRS, UMR7622, Biologie Moléculaire et Cellulaire du Développement, Université Pierre et Marie Curie, Paris, France.

Limb muscle formation is spread out over time and, consequently, muscle cells are not easy to target at any particular stages. We aimed to design a technique to study gene function in the different steps of limb muscle formation. We have associated transposon-mediated gene transfer and a tetracycline-dependent activation method with forelimb somite electroporation. In addition, we have established a new vector combining a differentiated-muscle-cell-specific promoter and the transposon system, which allows stable gene expression in limb differentiated muscle cells and not in muscle progenitors. Using these methods, we observed that conditional Fgf4 expression in muscle cells at the onset of fetal muscle differentiation and specific Fgf4 expression in differentiated muscle cells alter muscle fiber formation in chick limbs. Limb somite electroporation with these set of vectors allowing stable, conditional, and differentiated-muscle-specific expression of transgenes opens new perspectives for investigating gene function at various steps of limb muscle formation.
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http://dx.doi.org/10.1002/dvdy.22498DOI Listing
May 2011

The timing of emergence of muscle progenitors is controlled by an FGF/ERK/SNAIL1 pathway.

Dev Biol 2009 Sep 13;333(2):229-37. Epub 2009 May 13.

Developmental Biology Institute of Marseille Luminy (IBDML), CNRS UMR 6216, Université de la Méditerranée, Campus de Luminy, 13288 Marseille Cedex 09, France.

In amniotes, the dermomyotome is the source of all skeletal muscles of the trunk and the limbs. Trunk skeletal muscles form in two sequential stages: in the first stage, cells located at the four borders of the epithelial dermomyotome delaminate to generate the primary myotome, composed of post-mitotic, mononucleated myocytes. The epithelio-mesenchymal transition (EMT) of the central dermomyotome initiates the second stage of muscle formation, characterised by a massive entry of mitotic muscle progenitors from the central region of the dermomyotome into the primary myotome. The signals that regulate the timing of the dermomyotome EMT are unknown. Here, we propose that this process is regulated by an FGF signal emanating from the primary myotome, a known source of FGF. The over-expression of FGF results in a precocious EMT of the dermomyotome, while on the contrary, the inhibition of FGF signalling by the electoporation of a dominant-negative form of FGFR4 delays this process. Within the dermomyotome, FGF signalling triggers a MAPK/ERK pathway that leads to the activation of the transcription factor Snail1, a known regulator of EMT in a number of cellular contexts. The activation or the inhibition of the MAPK/ERK pathway and of Snail1 mimics that of FGF signalling and leads to an early or delayed EMT of the dermomyotome, respectively. Altogether, our results indicate that in amniotes, the primary myotome is an organizing center that regulates the timely entry of embryonic muscle progenitors within the muscle masses, thus initiating the growth phase of the trunk skeletal muscles.
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http://dx.doi.org/10.1016/j.ydbio.2009.05.544DOI Listing
September 2009

A molecular clock operates during chick autopod proximal-distal outgrowth.

J Mol Biol 2007 Apr 9;368(2):303-9. Epub 2007 Feb 9.

Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal.

Temporal control can be considered the fourth dimension in embryonic development. The identification of the somitogenesis molecular clock provided new insight into how embryonic cells measure time. We provide the first evidence of a molecular clock operating during chick fore-limb autopod outgrowth and patterning, by showing that the expression of the somitogenesis clock component hairy2 cycles in autopod chondrogenic precursor cells with a 6 h periodicity. We determined the length of time required to form an autopod skeletal limb element, and established a correlation between the latter and the periodicity of cyclic hairy2 gene expression. We suggest that temporal control exerted by cyclic gene expression can be a widespread mechanism providing cellular temporal information during vertebrate embryonic development.
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http://dx.doi.org/10.1016/j.jmb.2007.01.089DOI Listing
April 2007

Control of the segmentation process by graded MAPK/ERK activation in the chick embryo.

Proc Natl Acad Sci U S A 2005 Aug 29;102(32):11343-8. Epub 2005 Jul 29.

Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.

The regular spacing of somites during vertebrate embryogenesis involves a dynamic gradient of FGF signaling that controls the timing of maturation of cells in the presomitic mesoderm (PSM). How the FGF signal is transduced by PSM cells is unclear. Here, we first show that the FGF gradient is translated into graded activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway along the PSM in the chicken embryo. Using in ovo electroporation of PSM cells, we demonstrate that constitutive activation of ERK signaling in the PSM blocks segmentation by preventing maturation of PSM cells, thus phenocopying the overexpression of FGF8. Conversely, inhibition of ERK phosphorylation mimics a loss of function of FGF signaling in the PSM. Interestingly, video microscopy analysis of cell movements shows that ERK regulates the motility of PSM cells, suggesting that the decrease of cell movements along the PSM enables mesenchymal PSM cells to undergo proper segmentation. Together, our data demonstrate that ERK is the effector of the gradient of FGF in the PSM that controls the segmentation process.
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http://dx.doi.org/10.1073/pnas.0502933102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1183560PMC
August 2005

Ectopic Myf5 or MyoD prevents the neuronal differentiation program in addition to inducing skeletal muscle differentiation, in the chick neural tube.

Development 2004 Feb 14;131(4):713-23. Epub 2004 Jan 14.

Biologie du Développement, UMR 7622, Université P. et M. Curie, 9 Quai Saint-Bernard, Bât. C, 6(e)E, Case 24, 75252 Paris Cedex 05, France.

Forced expression of the bHLH myogenic factors, Myf5 and MyoD, in various mammalian cell lines induces the full program of myogenic differentiation. However, this property has not been extensively explored in vivo. We have taken advantage of the chick model to investigate the effect of electroporation of the mouse Myf5 and MyoD genes in the embryonic neural tube. We found that misexpression of either mouse Myf5 or MyoD in the chick neural tube leads to ectopic skeletal muscle differentiation, assayed by the expression of the myosin heavy chains in the neural tube and neural crest derivatives. We also showed that the endogenous neuronal differentiation program is inhibited under the influence of either ectopic mouse Myf5 or MyoD. We used this new system to analyse, in vivo, the transcriptional regulation between the myogenic factors. We found that MyoD and Myogenin expression can be activated by ectopic mouse Myf5 or MyoD, while Myf5 expression cannot be activated either by mouse MyoD or by itself. We also analysed the transcriptional regulation between the myogenic factors and the different genes involved in myogenesis, such as Mef2c, Pax3, Paraxis, Six1, Mox1, Mox2 and FgfR4. We established the existence of an unexpected regulatory loop between MyoD and FgfR4. The consequences for myogenesis are discussed.
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http://dx.doi.org/10.1242/dev.00967DOI Listing
February 2004