scholarly journals Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart

2020 ◽  
Author(s):  
Thomas J. Cahill ◽  
Xin Sun ◽  
Christophe Ravaud ◽  
Cristina Villa del Campo ◽  
Konstantinos Klaourakis ◽  
...  
Keyword(s):  
Heart Development ◽  
Lymphatic Vessel ◽  
Fetal Liver ◽  
Lymphatic Endothelial Cell ◽  
Vascular Plexus ◽  
Developing Heart ◽  
Vessel Growth ◽  
Summary Statement ◽  
And Function

AbstractMacrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that resident macrophages in the subepicardial compartment of the developing heart coincide with the emergence of new lymphatics and interact closely with the nascent lymphatic capillaries. Consequently, global macrophage-deficiency led to extensive vessel disruption with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and fetal liver. Moreover, Csf1r+ and Cx3cr1+ myeloid sub-lineages were found to play essential functions in the remodeling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was found to be required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.Summary statementTissue-resident macrophages are indispensable mediators of lymphatic vessel formation during heart development and function to remodel the vascular plexus.

scholarly journals Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart

Development ◽  
2021 ◽  
Vol 148 (3) ◽  
pp. dev194563 ◽  
Author(s):  
Thomas J. Cahill ◽  
Xin Sun ◽  
Christophe Ravaud ◽  
Cristina Villa del Campo ◽  
Konstantinos Klaourakis ◽  
...  
Keyword(s):  
Heart Development ◽  
Lymphatic Endothelial Cell ◽  
Innate Immune ◽  
Lymphatic Endothelium ◽  
Developing Heart ◽  
Foetal Liver ◽  
Vessel Growth ◽  
And Function ◽  
Insight Into

ABSTRACTMacrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1+ myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.

Role of VEGF-D and VEGFR-3 in developmental lymphangiogenesis, a chemicogenetic study in Xenopus tadpoles

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1740-1749 ◽  
Author(s):  
Annelii Ny ◽  
Marta Koch ◽  
Wouter Vandevelde ◽  
Martin Schneider ◽  
Christian Fischer ◽  
...  
Keyword(s):  
Critical Role ◽  
Small Animal ◽  
Lymphatic Endothelial Cell ◽  
Lymph Vessel ◽  
Small Animal Model ◽  
Morpholino Knockdown ◽  
Lymphatic Development ◽  
Lymph Heart ◽  
And Function

Abstract The importance of the lymphangiogenic factor VEGF-D and its receptor VEGFR-3 in early lymphatic development remains largely unresolved. We therefore investigated their role in Xenopus laevis tadpoles, a small animal model allowing chemicogenetic dissection of developmental lymphangiogenesis. Single morpholino antisense oligo knockdown of xVEGF-D did not affect lymphatic commitment, but transiently impaired lymphatic endothelial cell (LEC) migration. Notably, combined knockdown of xVEGF-D with xVEGF-C at suboptimal morpholino concentrations resulted in more severe migration defects and lymphedema formation than the corresponding single knockdowns. Knockdown of VEGFR-3 or treatment with the VEGFR-3 inhibitor MAZ51 similarly impaired lymph vessel formation and function and caused pronounced edema. VEGFR-3 silencing by morpholino knockdown, MAZ51 treatment, or xVEGF-C/D double knockdown also resulted in dilation and dysfunction of the lymph heart. These findings document a critical role of VEGFR-3 in embryonic lymphatic development and function, and reveal a previously unrecognized modifier role of VEGF-D in the regulation of embryonic lymphangiogenesis in frog embryos.

scholarly journals Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249068
Author(s):  
Elena C. Sigmund ◽  
Lilian Baur ◽  
Philipp Schineis ◽  
Jorge Arasa ◽  
Victor Collado-Diaz ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Knockout Mouse ◽  
Lymphatic Endothelial Cell ◽  
Peptide Hormone ◽  
Lymphatic Drainage ◽  
Adult Mice ◽  
Lymphatic Vasculature ◽  
Lymphatic Development ◽  
And Function

Atypical chemokine receptor ACKR3 (formerly CXCR7) is a scavenging receptor that has recently been implicated in murine lymphatic development. Specifically, ACKR3-deficiency was shown to result in lymphatic hyperplasia and lymphedema, in addition to cardiac hyperplasia and cardiac valve defects leading to embryonic lethality. The lymphatic phenotype was attributed to a lymphatic endothelial cell (LEC)-intrinsic scavenging function of ACKR3 for the vascular peptide hormone adrenomedullin (AM), which is also important during postnatal lymphangiogenesis. In this study, we investigated the expression of ACKR3 in the lymphatic vasculature of adult mice and its function in postnatal lymphatic development and function. We show that ACKR3 is widely expressed in mature lymphatics and that it exerts chemokine-scavenging activity in cultured murine skin-derived LECs. To investigate the role of LEC-expressed ACKR3 in postnatal lymphangiogenesis and function during adulthood, we generated and validated a lymphatic-specific, inducible ACKR3 knockout mouse. Surprisingly, in contrast to the reported involvement of ACKR3 in lymphatic development, our analyses revealed no contribution of LEC-expressed ACKR3 to postnatal lymphangiogenesis, lymphatic morphology and drainage function.

scholarly journals Trynity controls epidermal barrier function and respiratory tube maturation in Drosophila by modulating apical extracellular matrix nano-patterning

2018 ◽  
Author(s):  
Yuki Itakura ◽  
Sachi Inagaki ◽  
Housei Wada ◽  
Shigeo Hayashi
Keyword(s):  
Extracellular Matrix ◽  
Barrier Function ◽  
Essential Gene ◽  
Epidermal Barrier ◽  
Summary Statement ◽  
Domain Protein ◽  
And Function ◽  
Envelope Layer ◽  
Nano Patterning

AbstractThe outer surface of insects is covered by the cuticle, which is derived from the apical extracellular matrix (aECM). The aECM is secreted by epidermal cells during embryogenesis. The aECM exhibits large variations in structure, function, and constituent molecules, reflecting the enormous diversity in insect appearances. To investigate the molecular principles of aECM organization and function, here we studied the role of a conserved aECM protein, the ZP domain protein Trynity, in Drosophila melanogaster. We first identified trynity as an essential gene for epidermal barrier function. trynity mutation caused disintegration of the outermost envelope layer of the cuticle, resulting in small- molecule leakage and in growth and molting defects. In addition, the tracheal tubules of trynity mutants showed defects in pore-like structures of the cuticle, and the mutant tracheal cells failed to absorb luminal proteins and liquid. Our findings indicated that trynity plays essential roles in organizing nano-level structures in the envelope layer of the cuticle that both restrict molecular trafficking through the epidermis and promote the massive absorption pulse in the trachea.Summary StatementThe zona pellucida domain protein Trynity controls the structural organization and function of the apical extracellular matrix in the epidermis and trachea of Drosophila.

scholarly journals Dual role for fungal-specific outer kinetochore proteins during cell cycle and development in Magnaporthe oryzae

2018 ◽  
Author(s):  
Hiral Shah ◽  
Kanika Rawat ◽  
Harsh Ashar ◽  
Rajesh Patkar ◽  
Johannes Manjrekar
Keyword(s):  
Cell Cycle ◽  
Magnaporthe Oryzae ◽  
Complex Protein ◽  
Development And Differentiation ◽  
Multiple Cell ◽  
Summary Statement ◽  
Dam1 Complex ◽  
And Function ◽  
Anti Fungal

AbstractThe outer kinetochore DASH/DAM complex ensures proper spindle structure and chromosome segregation. While DASH complex protein requirement diverges among different yeasts, its role in filamentous fungi has not been investigated so far. We studied the dynamics and role of middle (Mis12) and outer (Dam1 and Ask1) kinetochore proteins in the filamentous fungal pathogen, Magnaporthe oryzae, which undergoes multiple cell cycle linked developmental transitions. Both Dam1 and Ask1, unlike Mis12, were recruited to the nucleus specifically during mitosis. While Dam1 was not required for viability, loss of its function (dam1Δ mutant) delayed mitotic progression, resulting in impaired conidial and hyphal development in Magnaporthe. Intriguingly, both Dam1 and Ask1 also localised to the hyphal tips, in the form of punctae oscillating back and forth from the growing ends, suggesting that Magnaporthe DASH complex proteins may play a non-canonical role in polarised growth during interphase, in addition to their function in nuclear segregation during mitosis. Impaired appressorial (infection structure) development and function in the dam1Δ mutant suggest that fungus-specific Dam1 complex proteins could be an attractive target for a novel anti-fungal strategy.Summary StatementDASH complex proteins are differentially recruited to the nucleus during cell division and are intriguingly involved in polarised growth during development and differentiation in the rice blast fungus.

scholarly journals Importance of Cx43 for Right Ventricular Function

2021 ◽  
Vol 22 (3) ◽  
pp. 987
Author(s):  
Kerstin Boengler ◽  
Susanne Rohrbach ◽  
Norbert Weissmann ◽  
Rainer Schulz
Keyword(s):  
Pulmonary Hypertension ◽  
Left Ventricle ◽  
Right Ventricular ◽  
Connexin 43 ◽  
Therapeutic Strategies ◽  
Cx43 Expression ◽  
Developing Heart ◽  
And Function ◽  
Rv Function

In the heart, connexins form gap junctions, hemichannels, and are also present within mitochondria, with connexin 43 (Cx43) being the most prominent connexin in the ventricles. Whereas the role of Cx43 is well established for the healthy and diseased left ventricle, less is known about the importance of Cx43 for the development of right ventricular (RV) dysfunction. The present article focusses on the importance of Cx43 for the developing heart. Furthermore, we discuss the expression and localization of Cx43 in the diseased RV, i.e., in the tetralogy of Fallot and in pulmonary hypertension, in which the RV is affected, and RV hypertrophy and failure occur. We will also introduce other Cx molecules that are expressed in RV and surrounding tissues and have been reported to be involved in RV pathophysiology. Finally, we highlight therapeutic strategies aiming to improve RV function in pulmonary hypertension that are associated with alterations of Cx43 expression and function.

scholarly journals The Iroquois Homeobox Gene Irx2 Is Not Essential for Normal Development of the Heart and Midbrain-Hindbrain Boundary in Mice

2003 ◽  
Vol 23 (22) ◽  
pp. 8216-8225 ◽  
Author(s):  
Mélanie Lebel ◽  
Pooja Agarwal ◽  
Chi Wa Cheng ◽  
M. Golam Kabir ◽  
Toby Y. Chan ◽  
...  
Keyword(s):  
Heart Development ◽  
Homeobox Gene ◽  
Mutant Mice ◽  
Phenotypic Analysis ◽  
Functional Roles ◽  
Developing Heart ◽  
Dynamic Expression ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Deficient Mice

ABSTRACT The Iroquois homeobox (Irx) genes have been implicated in the specification and patterning of several organs in Drosophila and several vertebrate species. Misexpression studies of chick, Xenopus, and zebra fish embryos have demonstrated that Irx genes are involved in the specification of the midbrain-hindbrain boundary. All six murine Irx genes are expressed in the developing heart, suggesting that they might possess distinct functions during heart development, and a role for Irx4 in normal heart development has been recently demonstrated by gene-targeting experiments. Here we describe the generation and phenotypic analysis of an Irx2-deficient mouse strain. By targeted insertion of a lacZ reporter gene into the Irx2 locus, we show that lacZ expression reproduces most of the endogenous Irx2 expression pattern. Despite the dynamic expression of Irx2 in the developing heart, nervous system, and other organs, Irx2-deficient mice are viable, are fertile, and appear to be normal. Although chick Irx2 has been implicated in the development of the midbrain-hindbrain region, we show that Irx2-deficient mice develop a normal midbrain-hindbrain boundary. Furthermore, Irx2-deficient mice have normal cardiac morphology and function. Functional compensation by other Irx genes might account for the absence of a phenotype in Irx2-deficient mice. Further studies of mutant mice of other Irx genes as well as compound mutant mice will be necessary to uncover the functional roles of these evolutionarily conserved transcriptional regulators in development and disease.

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