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

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.

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

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joana Esteves de Lima ◽  
Cédrine Blavet ◽  
Marie-Ange Bonnin ◽  
Estelle Hirsinger ◽  
Glenda Comai ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Lineage Tracing ◽  
Myotendinous Junction ◽  
Genetic Lineage ◽  
Limb Muscle ◽  
Lateral Plate Mesoderm ◽  
Loss Of Function ◽  
Sequencing Data ◽  
Lateral Plate ◽  
Bmp Signalling

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.

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

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.

scholarly journals Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Hajime Fukui ◽  
Takahiro Miyazaki ◽  
Renee Wei-Yan Chow ◽  
Hiroyuki Ishikawa ◽  
Hiroyuki Nakajima ◽  
...  
Keyword(s):  
Cell Number ◽  
Bmp Signaling ◽  
Hippo Signaling ◽  
Lateral Plate Mesoderm ◽  
Cardiomyocyte Proliferation ◽  
Heart Tube ◽  
Lateral Plate ◽  
Large Tumor ◽  
Developmental Potential ◽  
Anterior Lateral Plate Mesoderm

The differentiation of the lateral plate mesoderm cells into heart field cells constitutes a critical step in the development of cardiac tissue and the genesis of functional cardiomyocytes. Hippo signaling controls cardiomyocyte proliferation, but the role of Hippo signaling during early cardiogenesis remains unclear. Here, we show that Hippo signaling regulates atrial cell number by specifying the developmental potential of cells within the anterior lateral plate mesoderm (ALPM), which are incorporated into the venous pole of the heart tube and ultimately into the atrium of the heart. We demonstrate that Hippo signaling acts through large tumor suppressor kinase 1/2 to modulate BMP signaling and the expression of hand2, a key transcription factor that is involved in the differentiation of atrial cardiomyocytes. Collectively, these results demonstrate that Hippo signaling defines venous pole cardiomyocyte number by modulating both the number and the identity of the ALPM cells that will populate the atrium of the heart.

scholarly journals Cohesin Components Stag1 and Stag2 Differentially Influence Haematopoietic Mesoderm Development in Zebrafish Embryos

2020 ◽  
Vol 8 ◽  
Author(s):  
Sarada Ketharnathan ◽  
Anastasia Labudina ◽  
Julia A. Horsfield
Keyword(s):  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Three Dimensional ◽  
Genetic Dissection ◽  
Lateral Plate Mesoderm ◽  
Loss Of Function ◽  
Lateral Plate ◽  
Mesoderm Development ◽  
The Individual ◽  
Primitive Erythropoiesis

Cohesin is a multiprotein complex made up of core subunits Smc1, Smc3, and Rad21, and either Stag1 or Stag2. Normal haematopoietic development relies on crucial functions of cohesin in cell division and regulation of gene expression via three-dimensional chromatin organization. Cohesin subunit STAG2 is frequently mutated in myeloid malignancies, but the individual contributions of Stag variants to haematopoiesis or malignancy are not fully understood. Zebrafish have four Stag paralogues (Stag1a, Stag1b, Stag2a, and Stag2b), allowing detailed genetic dissection of the contribution of Stag1-cohesin and Stag2-cohesin to development. Here we characterize for the first time the expression patterns and functions of zebrafish stag genes during embryogenesis. Using loss-of-function CRISPR-Cas9 zebrafish mutants, we show that stag1a and stag2b contribute to primitive embryonic haematopoiesis. Both stag1a and stag2b mutants present with erythropenia by 24 h post-fertilization. Homozygous loss of either paralogue alters the number of haematopoietic/vascular progenitors in the lateral plate mesoderm. The lateral plate mesoderm zone of scl-positive cells is expanded in stag1a mutants with concomitant loss of kidney progenitors, and the number of spi1-positive cells are increased, consistent with skewing toward primitive myelopoiesis. In contrast, stag2b mutants have reduced haematopoietic/vascular mesoderm and downregulation of primitive erythropoiesis. Our results suggest that Stag1 and Stag2 proteins cooperate to balance the production of primitive haematopoietic/vascular progenitors from mesoderm.

scholarly journals Essential roles of zebrafish bmp2a, fgf10, and fgf24 in the specification of the ventral pancreas

2012 ◽  
Vol 23 (5) ◽  
pp. 945-954 ◽  
Author(s):  
François Naye ◽  
Marianne L. Voz ◽  
Nathalie Detry ◽  
Matthias Hammerschmidt ◽  
Bernard Peers ◽  
...  
Keyword(s):  
Fibroblast Growth ◽  
Lateral Plate Mesoderm ◽  
Loss Of Function ◽  
Lateral Plate ◽  
Bmp Pathway ◽  
Ventral Pancreas ◽  
Pancreas Agenesis ◽  
Gut Endoderm ◽  
Hepatic Markers

In vertebrates, pancreas and liver arise from bipotential progenitors located in the embryonic gut endoderm. Bone morphogenic protein (BMP) and fibroblast growth factor (FGF) signaling pathways have been shown to induce hepatic specification while repressing pancreatic fate. Here we show that BMP and FGF factors also play crucial function, at slightly later stages, in the specification of the ventral pancreas. By analyzing the pancreatic markers pdx1, ptf1a, and hlxb9la in different zebrafish models of BMP loss of function, we demonstrate that the BMP pathway is required between 20 and 24 h postfertilization to specify the ventral pancreatic bud. Knockdown experiments show that bmp2a, expressed in the lateral plate mesoderm at these stages, is essential for ventral pancreas specification. Bmp2a action is not restricted to the pancreatic domain and is also required for the proper expression of hepatic markers. By contrast, through the analysis of fgf10−/−; fgf24−/− embryos, we reveal the specific role of these two FGF ligands in the induction of the ventral pancreas and in the repression of the hepatic fate. These mutants display ventral pancreas agenesis and ectopic masses of hepatocytes. Overall, these data highlight the dynamic role of BMP and FGF in the patterning of the hepatopancreatic region.

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

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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