Hedgehog–BMP signalling establishes dorsoventral patterning in lateral plate mesoderm to trigger gonadogenesis in chicken embryos

AbstractPositional 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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BMP signalling directs a fibroblast-to-myoblast conversion at the connective tissue/muscle interface to pattern limb muscles

10.1101/2020.07.20.211342 ◽

2020 ◽

Author(s):

Joana Esteves de Lima ◽

Cédrine Blavet ◽

Marie-Ange Bonnin ◽

Estelle Hirsinger ◽

Glenda Comai ◽

...

Keyword(s):

Connective Tissue ◽

Limb Development ◽

Lineage Tracing ◽

Genetic Lineage ◽

Lateral Plate Mesoderm ◽

Loss Of Function ◽

Sequencing Data ◽

Lateral Plate ◽

Myogenic Cells ◽

Bmp Signalling

AbstractPositional information driving limb muscle patterning is contained in lateral plate mesoderm-derived tissues, such as tendon or muscle connective tissue but not in myogenic cells themselves. The long-standing consensus is that myogenic cells originate from the somitic mesoderm, while connective tissue fibroblasts originate from the lateral plate mesoderm. We challenged this model using cell and genetic lineage tracing experiments in birds and mice, respectively, and identified a subpopulation of myogenic cells at the muscle tips close to tendons originating from the lateral plate mesoderm and derived from connective tissue gene lineages. Analysis of single-cell RNA-sequencing data obtained from limb cells at successive developmental stages revealed a subpopulation of cells displaying a dual muscle and connective tissue signature, in addition to independent muscle and connective tissue populations. Active BMP signalling was detected in this junctional cell sub-population and at the tendon/muscle interface in developing limbs. BMP gain- and loss-of-function experiments performed in vivo and in vitro showed that this signalling pathway regulated a fibroblast-to-myoblast conversion. We propose that localised BMP signalling converts a subset of lateral plate mesoderm-derived fibroblasts to a myogenic fate and establishes a boundary of fibroblast-derived myonuclei at the muscle/tendon interface to control the muscle pattern during limb development.

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CBFβ initiates the hematopoietic stem cell program without obligatory binding to RUNX

10.1101/172957 ◽

2017 ◽

Author(s):

Aldo Ciau-Uitz ◽

Philip Pinheiro ◽

Arif Kirmizitas ◽

Claire Fernandez ◽

Roger Patient

Keyword(s):

Mutant Form ◽

List Type ◽

Lateral Plate Mesoderm ◽

Lateral Plate ◽

Hematopoietic Stem ◽

Binding Partner ◽

Gene Regulatory ◽

Bmp Signalling ◽

Regulatory Functions ◽

First Time

SUMMARYHematopoietic stem cells (HSCs) emerge from hemogenic endothelium (HE) localised in the embryonic dorsal aorta (DA). Here we show that Runx1, a transcription factor essential for HSC emergence, controls HE establishment in the absence of its non-DNA-binding partner, CBFβ, and that a CBFβ-binding-deficient Runx1 mutant form can activate the HE program in the DA. Nevertheless, CBFβ is also essential for HSC emergence by regulating the specification of definitive hemangioblasts (DHs), the precursors of the DA and HE, in the lateral plate mesoderm where it mediates VEGFA induction by BMP signalling. Surprisingly, no Runx gene is expressed in DHs and the pharmacological inhibition of CBFβ binding to Runx is not detrimental for DH, confirming that CBFβ functions independently of Runx. Thus, we have uncovered, for the first time, that CBFβ regulates gene expression without Runx, breaking the dogma in which CBFβ ‘s gene regulatory functions are strictly dependent on its binding to Runx.HIGHLIGHTSRunx1 and CBFβ play independent roles in the establishment of the HSC lineageRunx1 binding to CBFβ is not required for HE establishmentCBFβ is downstream of BMP and regulates endogenous VEGFA expression in DHBinding to Runx is not obligatory for CBFβ function

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Mesodermal subdivision along the mediolateral axis in chicken controlled by different concentrations of BMP-4

Development ◽

10.1242/dev.124.10.1975 ◽

1997 ◽

Vol 124 (10) ◽

pp. 1975-1984 ◽

Cited By ~ 27

Author(s):

A. Tonegawa ◽

N. Funayama ◽

N. Ueno ◽

Y. Takahashi

Keyword(s):

Early Development ◽

Molecular Mechanisms ◽

Lateral Plate Mesoderm ◽

Tgf Beta ◽

Presomitic Mesoderm ◽

Lateral Plate ◽

Chicken Embryos ◽

Cos Cells ◽

Low Level ◽

High Level

Molecular mechanisms by which the mesoderm is subdivided along the mediolateral axis in early chicken embryos have been studied. When the presomitic mesoderm (medial mesoderm) was transplanted into the lateral plate, the graft was transformed into lateral plate tissue, indicating that the primitive somite was not fully committed and that the lateral plate has a cue for mesodermal lateralization. Since the lateral plate expresses a high level of BMP-4 mRNA, a member of the TGF-beta family, we hypothesized that it is the molecule responsible for the lateralization of the somite. To test this, we transplanted COS cells producing BMP-4 into the presomitic region. Those cells locally prevented the presomitic cells from differentiating into somites, converting them instead into lateral plate mesoderm, which was revealed by expression of cytokeratin mRNA, a marker for the lateral plate. The effect was dependent on the level of effective BMP-4: with a high level of BMP-4, the somite was transformed completely to lateral plate; with a low level, the somite formed but was occupied by the lateral somitic component expressing cSim 1, a marker for the lateral somite. These results suggest that different thresholds of effective BMP-4 determine distinct subtypes of the mesoderm as a lateralizer during early development.

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Endocardial differentiation in zebrafish occurs during early somitogenesis and is dependent on BMP and etv2 signalling

10.1101/654525 ◽

2019 ◽

Author(s):

Samuel J Capon ◽

Kelly A Smith

Keyword(s):

Vascular Endothelial ◽

Lateral Plate Mesoderm ◽

Loss Of Function ◽

Lateral Plate ◽

Molecular Identity ◽

Cardiovascular Biology ◽

Bmp Signalling ◽

Anterior Lateral Plate Mesoderm ◽

Function Models ◽

Signalling Cascade

AbstractThe endocardium and adjacent vascular endothelial network share a number of molecular markers however there are distinct physiological functions of these tissues. What distinguishes these lineages on a molecular level remains an important, unanswered question in cardiovascular biology. We have identified the Gt(SAGFF27C); Tg(4xUAS:egfp) line as a marker of early endocardial development and used this line to examine endocardial differentiation. Our results show that the endocardium emerges from the anterior lateral plate mesoderm at the 8-somite stage (13 hpf). Analysis in a number of loss-of-function models showed that whilst nkx2.5, hand2 and tal1 loss-of-function have no effect on the endocardial progenitor domain, both etv2 loss-of-function and inhibition of BMP signalling reduce the endocardial domain. Furthermore, manipulating BMP signalling alters etv2 expression. Together, these results describe the onset of endocardial molecular identity and suggest a signalling cascade whereby BMP signalling acts upstream of etv2 to direct differentiation of endocardial progenitors.

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