scholarly journals A conserved regulatory program drives emergence of the lateral plate mesoderm

2018 ◽  
Author(s):  
Karin D. Prummel ◽  
Christopher Hess ◽  
Susan Nieuwenhuize ◽  
Hugo J. Parker ◽  
Katherine W. Rogers ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Transcription Factors ◽  
Connective Tissue ◽  
Live Imaging ◽  
Lineage Tracing ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Mesodermal Cell ◽  
Reporter Activity ◽  
Vertebrate Embryo

AbstractCardiovascular lineages develop together with kidney, smooth muscle, and limb connective tissue progenitors from the lateral plate mesoderm (LPM). How the LPM initially emerges and how its downstream fates are molecularly interconnected remain unknown. Here, we isolated a pan-LPM enhancer in the zebrafish draculin (drl) gene that provides specific LPM reporter activity from early gastrulation. In toto live imaging and lineage tracing of drl-based reporters captured the dynamic LPM emergence as lineage-restricted mesendoderm field. The drl pan-LPM enhancer responds to the transcription factors EomesoderminA, FoxH1, and MixL1 that combined with Smad activity drive LPM emergence. We uncovered specific drl reporter activity in LPM-corresponding territories of several chordates including chicken, axolotl, lamprey, Ciona, and amphioxus, revealing a universal upstream LPM program. Altogether, our work provides a mechanistic framework for LPM emergence as defined progenitor field, possibly representing an ancient mesodermal cell state that predates the primordial vertebrate embryo.

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 Homeobox genes and connective tissue patterning

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 693-705 ◽  
Author(s):  
G. Oliver ◽  
R. Wehr ◽  
N.A. Jenkins ◽  
N.G. Copeland ◽  
B.N. Cheyette ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Connective Tissue ◽  
Early Development ◽  
Molecular Mechanisms ◽  
Homeobox Genes ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Tissue Patterning

In vertebrates, limb tendons are derived from cells that migrate from the lateral plate mesoderm during early development. While some of the developmental steps leading to the formation of these tissues are known, little is known about the molecular mechanisms controlling them. We have identified two murine homeobox-containing genes, Six 1 and Six 2, which are expressed in a complementary fashion during the development of limb tendons. Transcripts for both genes are found in different sets of phalangeal tendons. Six 1 and Six 2 also are expressed in skeletal and smooth muscle, respectively. These genes may participate in the patterning of the distal tendons of the limb phalanges by setting positional values along the limb axes.

scholarly journals HOXA5 protein expression and genetic fate mapping show lineage restriction in the developing musculoskeletal system

2018 ◽  
Vol 62 (11-12) ◽  
pp. 785-796
Author(s):  
Miriam A. Holzman ◽  
Jenna M. Bergmann ◽  
Maya Feldman ◽  
Kim Landry-Truchon ◽  
Lucie Jeannotte ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hox Genes ◽  
Lineage Tracing ◽  
Genetic Lineage ◽  
Lateral Plate Mesoderm ◽  
Embryonic Cells ◽  
Connective Tissues ◽  
Lateral Plate ◽  
Direct Role ◽  
Skeletal Patterning

HOX proteins act during development to regulate musculoskeletal morphology. HOXA5 patterns skeletal structures surrounding the cervical-thoracic transition including the vertebrae, ribs, sternum and forelimb girdle. However, the tissue types in which it acts to pattern the skeleton, and the ultimate fates of embryonic cells that activate Hoxa5 expression are unknown. A detailed characterization of HOXA5 expression by immunofluorescence was combined with Cre/LoxP genetic lineage tracing to map the fate of Hoxa5 expressing cells in axial musculoskeletal tissues and in their precursors, the somites and lateral plate mesoderm. HOXA5 protein expression is dynamic and spatially restricted in derivatives of both the lateral plate mesoderm and somites, including a subset of the lateral sclerotome, suggesting a local role in regulating early skeletal patterning. HOXA5 expression persists from somite stages through late development in differentiating skeletal and connective tissues, pointing to a continuous and direct role in skeletal patterning. In contrast, HOXA5 expression is excluded from the skeletal muscle and muscle satellite cell lineages. Furthermore, the descendants of Hoxa5-expressing cells, even after HOXA5 expression has extinguished, never contribute to these lineages. Together, these findings suggest cell autonomous roles for HOXA5 in skeletal development, as well as non-cell autonomous functions in muscle through expression in surrounding connective tissues. They also support the notion that different Hox genes display diverse tissue specificities and locations to achieve their patterning activity.

scholarly journals Analyses of Avascular Mutants Reveal Unique Transcriptomic Signature of Non-conventional Endothelial Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Boryeong Pak ◽  
Christopher E. Schmitt ◽  
Woosoung Choi ◽  
Jun-Dae Kim ◽  
Orjin Han ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Lineage Tracing ◽  
Molecular Characteristics ◽  
Lateral Plate Mesoderm ◽  
Rna Seq ◽  
Developmental History ◽  
Lateral Plate ◽  
Developmental Origin ◽  
Transcriptomic Signature

Endothelial cells appear to emerge from diverse progenitors. However, to which extent their developmental origin contributes to define their cellular and molecular characteristics remains largely unknown. Here, we report that a subset of endothelial cells that emerge from the tailbud possess unique molecular characteristics that set them apart from stereotypical lateral plate mesoderm (LPM)-derived endothelial cells. Lineage tracing shows that these tailbud-derived endothelial cells arise at mid-somitogenesis stages, and surprisingly do not require Npas4l or Etsrp function, indicating that they have distinct spatiotemporal origins and are regulated by distinct molecular mechanisms. Microarray and single cell RNA-seq analyses reveal that somitogenesis- and neurogenesis-associated transcripts are over-represented in these tailbud-derived endothelial cells, suggesting that they possess a unique transcriptomic signature. Taken together, our results further reveal the diversity of endothelial cells with respect to their developmental origin and molecular properties, and provide compelling evidence that the molecular characteristics of endothelial cells may reflect their distinct developmental history.

scholarly journals Unique morphogenetic signatures define mammalian neck muscles and associated connective tissues

2018 ◽  
Author(s):  
Eglantine Heude ◽  
Marketa Tesarova ◽  
Elizabeth M. Sefton ◽  
Estelle Jullian ◽  
Noritaka Adachi ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Connective Tissue ◽  
3D Model ◽  
Neck Muscles ◽  
Genetic Networks ◽  
Trunk Muscles ◽  
Cell Populations ◽  
Lateral Plate Mesoderm ◽  
Connective Tissues ◽  
Lateral Plate

ABSTRACTIn vertebrates, head and trunk muscles develop from different mesodermal populations and are regulated by distinct genetic networks. Neck muscles at the head-trunk interface remain poorly defined due to their complex morphogenesis and dual mesodermal origins. Here, we use genetically modified mice to establish a 3D model that integrates regulatory genes, cell populations and morphogenetic events that define this transition zone. We show that the evolutionary conserved cucullaris-derived muscles originate from posterior cardiopharyngeal mesoderm, not lateral plate mesoderm, and we define new boundaries for neural crest and mesodermal contributions to neck connective tissue. Furthermore, lineage studies and functional analysis of Tbx1- and Pax3-null mice reveal a unique genetic program for somitic neck muscles that is distinct from that of somitic trunk muscles. Our findings unveil the embryological and developmental requirements underlying tetrapod neck myogenesis and provide a blueprint to investigate how muscle subsets are selectively affected in some human myopathies.

scholarly journals Human iPS-derived pre-epicardial cells direct cardiomyocyte aggregation expansion and organization in vitro

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jun Jie Tan ◽  
Jacques P. Guyette ◽  
Kenji Miki ◽  
Ling Xiao ◽  
Gurbani Kaur ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Spatial Organization ◽  
Three Dimensional ◽  
Calcium Handling ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Epicardial Cells ◽  
Tissue Organization ◽  
Cell Layers

AbstractEpicardial formation is necessary for normal myocardial morphogenesis. Here, we show that differentiating hiPSC-derived lateral plate mesoderm with BMP4, RA and VEGF (BVR) can generate a premature form of epicardial cells (termed pre-epicardial cells, PECs) expressing WT1, TBX18, SEMA3D, and SCX within 7 days. BVR stimulation after Wnt inhibition of LPM demonstrates co-differentiation and spatial organization of PECs and cardiomyocytes (CMs) in a single 2D culture. Co-culture consolidates CMs into dense aggregates, which then form a connected beating syncytium with enhanced contractility and calcium handling; while PECs become more mature with significant upregulation of UPK1B, ITGA4, and ALDH1A2 expressions. Our study also demonstrates that PECs secrete IGF2 and stimulate CM proliferation in co-culture. Three-dimensional PEC-CM spheroid co-cultures form outer smooth muscle cell layers on cardiac micro-tissues with organized internal luminal structures. These characteristics suggest PECs could play a key role in enhancing tissue organization within engineered cardiac constructs in vitro.

scholarly journals Paraxial Nodal Expression Reveals a Novel Conserved Structure of the Left-Right Organizer in Four Mammalian Species

2016 ◽  
Vol 201 (2) ◽  
pp. 77-87 ◽  
Author(s):  
Silke S. Schröder ◽  
Nikoloz Tsikolia ◽  
Annette Weizbauer ◽  
Isabelle Hue ◽  
Christoph Viebahn
Keyword(s):  
Histological Analysis ◽  
Mammalian Species ◽  
Model Organism ◽  
Lateral Plate Mesoderm ◽  
Open Surface ◽  
Nodal Domain ◽  
Expression Domain ◽  
Lateral Plate ◽  
Vertebrate Embryo ◽  
Left Right Asymmetry

Nodal activity in the left lateral plate mesoderm is a conserved sign of irreversible left-right asymmetry at early somite stages of the vertebrate embryo. An earlier, paraxial nodal domain accompanies the emergence and initial extension of the notochord and is either left-sided, as in the chick and pig, or symmetrical, as in the mouse and rabbit; intriguingly, this interspecific dichotomy is mirrored by divergent morphological features of the posterior notochord (also known as the left-right organizer), which is ventrally exposed to the yolk sac cavity and carries motile cilia in the latter 2 species only. By introducing the cattle embryo as a new model organism for early left-right patterning, we present data to establish 2 groups of mammals characterized by both the morphology of the left-right organizer and the dynamics of paraxial nodal expression: presence and absence of a ventrally open surface of the early (plate-like) posterior notochord correlates with a symmetrical (in mice and rabbits) versus an asymmetrical (in pigs and cattle) paraxial nodal expression domain next to the notochordal plate. High-resolution histological analysis reveals that the latter domain defines in all 4 mammals a novel ‘parachordal' axial mesoderm compartment, the topography of which changes according to the specific regression of the similarly novel subchordal mesoderm during the initial phases of notochord development. In conclusion, the mammalian axial mesoderm compartment (1) shares critical conserved features despite the marked differences in early notochord morphology and early left-right patterning and (2) provides a dynamic topographical framework for nodal activity as part of the mammalian left-right organizer.

scholarly journals Vascular remodeling of the vitelline artery initiates extravascular emergence of hematopoietic clusters

Blood ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 3435-3444 ◽  
Author(s):  
Ann C. Zovein ◽  
Kirsten A. Turlo ◽  
Ryan M. Ponec ◽  
Maureen R. Lynch ◽  
Kevin C. Chen ◽  
...  
Keyword(s):  
Mesenteric Artery ◽  
Lineage Tracing ◽  
Stem Cell Markers ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Hematopoietic Stem ◽  
Blood Island ◽  
Vascular Beds ◽  
Large Clusters ◽  
Arterial Endothelium

Abstract The vitelline artery is a temporary structure that undergoes extensive remodeling during midgestation to eventually become the superior mesenteric artery (also called the cranial mesenteric artery, in the mouse). Here we show that, during this remodeling process, large clusters of hematopoietic progenitors emerge via extravascular budding and form structures that resemble previously described mesenteric blood islands. We demonstrate through fate mapping of vascular endothelium that these mesenteric blood islands are derived from the endothelium of the vitelline artery. We further show that the vitelline arterial endothelium and subsequent blood island structures originate from a lateral plate mesodermal population. Lineage tracing of the lateral plate mesoderm demonstrates contribution to all hemogenic vascular beds in the embryo, and eventually, all hematopoietic cells in the adult. The intraembryonic hematopoietic cell clusters contain viable, proliferative cells that exhibit hematopoietic stem cell markers and are able to further differentiate into myeloid and erythroid lineages. Vitelline artery–derived hematopoietic progenitor clusters appear between embryonic day 10 and embryonic day 10.75 in the caudal half of the midgut mesentery, but by embryonic day 11.0 are sporadically found on the cranial side of the midgut, thus suggesting possible extravascular migration aided by midgut rotation.

scholarly journals Control of mouse limb initiation and antero-posterior patterning by Meis transcription factors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Irene Delgado ◽  
Giovanna Giovinazzo ◽  
Susana Temiño ◽  
Yves Gauthier ◽  
Aurelio Balsalobre ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Limb Development ◽  
Critical Factor ◽  
Interaction Networks ◽  
Lateral Plate Mesoderm ◽  
Lateral Plate ◽  
Hox Proteins ◽  
Mouse Limb ◽  
Limb Initiation

AbstractMeis1 and Meis2 are homeodomain transcription factors that regulate organogenesis through cooperation with Hox proteins. Elimination of Meis genes after limb induction has shown their role in limb proximo-distal patterning; however, limb development in the complete absence of Meis function has not been studied. Here, we report that Meis1/2 inactivation in the lateral plate mesoderm of mouse embryos leads to limb agenesis. Meis and Tbx factors converge in this function, extensively co-binding with Tbx to genomic sites and co-regulating enhancers of Fgf10, a critical factor in limb initiation. Limbs with three deleted Meis alleles show proximal-specific skeletal hypoplasia and agenesis of posterior skeletal elements. This failure in posterior specification results from an early role of Meis factors in establishing the limb antero-posterior prepattern required for Shh activation. Our results demonstrate roles for Meis transcription factors in early limb development and identify their involvement in previously undescribed interaction networks that regulate organogenesis.

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