CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart

Bonet, Fernando; Pereira, Paulo N. G.; Bover, Oriol; Marques, Sara; Inácio, José M.; Belo, José António

doi:10.1002/dvdy.24670

Cited by 19 publications

(31 citation statements)

References 48 publications

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“…Yet, this population was fully absent from flt4 -/- and vegfc +/ - hearts, pointing to an additional source, other than coronary ECs, for Vegfc. While Vegfc has been previously shown to be expressed in maturing coronary artery ECs (Su et al, 2018), supporting a role of blood vessels in guiding lymphatic growth, Vegfc and Ccbe1 (Bonet et al, 2018) expression has also been detected in the epicardium in mice (Chen et al, 2014b), as well as in fish CMs under certain conditions (Marín-Juez et al, 2016). As a whole, the formation of the different lymphatic subsets in zebrafish, clearly follows the tissue requirements.…”

Section: Discussionmentioning

confidence: 88%

Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration

Gancz¹,

Raftrey

Perlmoter³

et al. 2019

eLife

155

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In recent years, there has been increasing interest in the role of lymphatics in organ repair and regeneration, due to their importance in immune surveillance and fluid homeostasis. Experimental approaches aimed at boosting lymphangiogenesis following myocardial infarction in mice, were shown to promote healing of the heart. Yet, the mechanisms governing cardiac lymphatic growth remain unclear. Here, we identify two distinct lymphatic populations in the hearts of zebrafish and mouse, one that forms through sprouting lymphangiogenesis, and the other by coalescence of isolated lymphatic cells. By tracing the development of each subset, we reveal diverse cellular origins and differential response to signaling cues. Finally, we show that lymphatic vessels are required for cardiac regeneration in zebrafish as mutants lacking lymphatics display severely impaired regeneration capabilities. Overall, our results provide novel insight into the mechanisms underlying lymphatic formation during development and regeneration, opening new avenues for interventions targeting specific lymphatic populations.

show abstract

Section: Discussionmentioning

confidence: 88%

Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration

Gancz¹,

Raftrey

Perlmoter³

et al. 2019

eLife

155

View full text Add to dashboard Cite

show abstract

“…These peritruncal vessels were remodeled and interconnected with the aortic endothelium (Chen et al, 2014a(Chen et al, , 2014bIvins et al, 2015;Thé veniau-Ruissy et al, 2016). The first step requires several molecules including VEGF-C (Chen et al, 2014a(Chen et al, , 2014b, C-X-C motif chemokine ligand 12 (Ivins et al, 2015), and the collagen-and calcium-binding EGF-like domains 1 protein (Bonet et al, 2018). Deletion of these signals results in a lack of ASVs and hypoplastic peritruncal CVs, leading to a decrease in the number of CA stems (Chen et al, 2014a(Chen et al, , 2014bIvins et al, 2015;Thé veniau-Ruissy et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Semaphorin3E-PlexinD1 signaling in coronary artery and lymphatic vessel development with clinical implications in myocardial recovery

et al. 2021

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Summary Blood and lymphatic vessels surrounding the heart develop through orchestrated processes from cells of different origins. In particular, cells around the outflow tract which constitute a primordial transient vasculature, referred to as aortic subepicardial vessels, are crucial for the establishment of coronary artery stems and cardiac lymphatic vessels. Here, we revealed that the epicardium and pericardium-derived Semaphorin 3E (Sema3E) and its receptor, PlexinD1, play a role in the development of the coronary stem, as well as cardiac lymphatic vessels. In vitro analyses demonstrated that Sema3E may demarcate areas to repel PlexinD1-expressing lymphatic endothelial cells, resulting in proper coronary and lymphatic vessel formation. Furthermore, inactivation of Sema3E-PlexinD1 signaling improved the recovery of cardiac function by increasing reactive lymphangiogenesis in an adult mouse model of myocardial infarction. These findings may lead to therapeutic strategies that target Sema3E-PlexinD1 signaling in coronary artery diseases.

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“…Mafb mutant mice do not survive after birth, presenting with respiratory failure and consequent cyanosis. These phenotypes could be seen as similar to lymphatic deficient Ccbe1 knockout mice, which fail to inflate their lungs after birth and also display cardiac phenotypes 48,49 . However, unlike Ccbe1 ‐deficient mice, Mafb mutant lungs contain lymphatic vessels.…”

Section: Discussionmentioning

confidence: 87%

MAFB modulates the maturation of lymphatic vascular networks in mice

Rondon‐Galeano

Skoczylas

Bower

et al. 2020

Developmental Dynamics

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Background: Lymphatic vessels play key roles in tissue fluid homeostasis, immune cell trafficking and in diverse disease settings. Lymphangiogenesis requires lymphatic endothelial cell (LEC) differentiation, proliferation, migration, and coordinated network formation, yet the transcriptional regulators underpinning these processes remain to be fully understood. The transcription factor MAFB was recently identified as essential for lymphangiogenesis in zebrafish and in cultured human LECs. MAFB is activated in response to VEGFC-VEGFR3 signaling and acts as a downstream effector. However, it remains unclear if the role of MAFB in lymphatic development is conserved in the mammalian embryo. Results: We generated a Mafb loss-of-function mouse using CRISPR/Cas9 gene editing. Mafb mutant mice presented with perinatal lethality associated with cyanosis. We identify a role for MAFB in modifying lymphatic network morphogenesis in the developing dermis, as well as developing and postnatal diaphragm. Furthermore, mutant vessels displayed excessive smooth muscle cell coverage, suggestive of a defect in the maturation of lymphatic networks. Conclusions: This work confirms a conserved role for MAFB in murine lymphatics that is subtle and modulatory and may suggest redundancy in MAF family transcription factors during lymphangiogenesis.

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CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart

Abstract: CCBE1 is essential for coronary vessel formation, independent of their embryonic origin, and is also necessary for peritruncal vessel growth and proper CA stem patterning. Developmental Dynamics 247:1135-1145, 2018. © 2018 Wiley Periodicals, Inc.

Cited by 19 publications

References 48 publications

Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration

Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration

Semaphorin3E-PlexinD1 signaling in coronary artery and lymphatic vessel development with clinical implications in myocardial recovery

MAFB modulates the maturation of lymphatic vascular networks in mice

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