mafba and mafbb differentially regulate lymphatic endothelial cell migration in topographically distinct manners

Arnold, Hannah; Panara, Virginia; Hußmann, Melina; Filipek-Górniok, Beata; Skoczylas, Renae; Gloger, Marleen; Allalou, Amin; Hogan, Benjamin M.; Schulte‐Merker, Stefan; Koltowska, Katarzyna

doi:10.1016/j.celrep.2022.110982

Cited by 7 publications

(19 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As this element is highly conserved across vertebrates, we used a P -value cut-off of 1e-02 for our MEME Suite ( Bailey and Elkan, 1994 ) and TOMTOM ( Gupta et al, 2007 ) to determine the motifs and putative transcription factor binding sites present. We identified conserved binding sites for multiple known lymphatic regulators, such as Gata2, Nfatc1, Mafb, Sox18, Prox1 ( Arnold et al, 2022 ; Geng et al, 2016 ; Kazenwadel et al, 2015 ; Koltowska et al, 2015b ; Shin et al, 2019 ) and the retinoic acid receptors Rarb and Rxrg ( Bowles et al, 2014 ; Marino et al, 2011 ). We also found putative sites for TFs which have been implied in regulation of Prox1 expression or are related to endothelial cell (EC) identity such as Tfe3, Ets::Foxo1, Prdm1 and Klf4 ( Dieterich et al, 2015 ; Niimi et al, 2019 ; Park et al, 2014 ; Pham et al, 2007 ; Tai-Nagara et al, 2020 ; De Val et al, 2008 ; Yoshimatsu et al, 2011 ) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…S1J,K ; Tables S4,S5 ). In order to test the functional importance of the predicted binding sites, we took advantage of the mafba uq4bh and mafbb ub47bh mutant lines available in our lab ( Arnold et al, 2022 ; Koltowska et al, 2015b ). Quantification of the activity of + 15.2prox1a in the mutant lines revealed a 60% reduction in enhancer activity in mafba mutants and 85% in double mutants ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…S3C,D ) . This broader expression in the facial LECs is probably due to additional putative TF binding sites present in the sequence which regulate zebrafish lymphangiogenesis, such as Mafb ( Arnold et al, 2022 ; Koltowska et al, 2015b ). The + 15.2prox1a enhancer does not appear to be accessible in either LECs or BECs at 4 dpf, which could be due to the dynamic activity of this element.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Multiple cis-regulatory elements control prox1a expression in distinct lymphatic vascular beds

Panara,

Yu,

Peng

et al. 2024

Development

Self Cite

View full text Add to dashboard Cite

During embryonic development, lymphatic endothelial cell (LEC) precursors are distinguished from blood endothelial cells by the expression of Prospero-related homeobox 1 (Prox1), which is essential for lymphatic vasculature formation in mouse and zebrafish. Prox1 expression initiation precedes LEC sprouting and migration, serving as the marker of specified LECs. Despite its crucial role in lymphatic development, Prox1 upstream regulation in LECs remains to be uncovered. SOX18 and COUP-TFII are thought to regulate Prox1 in mice by binding its promoter region. However, the specific regulation of Prox1 expression in LECs remains to be studied in detail. Here, we used evolutionary conservation and chromatin accessibility to identify enhancers located in the proximity of zebrafish prox1a active in developing LECs. We confirmed the functional role of the identified sequences through CRISPR/Cas9 mutagenesis of a lymphatic valve enhancer. The deletion of this region results in impaired valve morphology and function. Overall, our results reveal an intricate control of prox1a expression through a collection of enhancers. Ray-finned fish-specific distal enhancers drive pan-lymphatic expression, whereas vertebrate-conserved proximal enhancers refine expression in functionally distinct subsets of lymphatic endothelium.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Multiple cis-regulatory elements control prox1a expression in distinct lymphatic vascular beds

Panara,

Yu,

Peng

et al. 2024

Development

Self Cite

View full text Add to dashboard Cite

show abstract

“…Transcriptional regulation during lymphangiogenesis is strictly controlled, and recent evidence suggests the specific functions of several key transcription factors in lymphangiogenesis. The transcription factor V-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB), which is involved in the differentiation of various cell types, regulates the transcriptional changes invoked by VEGF-C in LECs ( Dieterich et al, 2015 ; Dieterich et al, 2020 ; Rondon-Galeano et al, 2020 ; Arnold et al, 2022 ). MAFB induces the expression of PROX1 , other transcription factors and markers of differentiated LECs, indicating the role of MAFB in the maintenance of the mature LEC phenotype ( Dieterich et al, 2015 ).…”

Section: The Development Of the Lymphatic Vascular Systemmentioning

confidence: 99%

Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation

Ujiie

Kume

2022

Front. Physiol.

View full text Add to dashboard Cite

The lymphatic system is crucial for the maintenance of interstitial fluid and protein homeostasis. It has important roles in collecting excess plasma and interstitial fluid leaked from blood vessels, lipid absorption and transportation in the digestive system, and immune surveillance and response. The development of lymphatic vessels begins during fetal life as lymphatic endothelial progenitor cells first differentiate into lymphatic endothelial cells (LECs) by expressing the master lymphatic vascular regulator, prospero-related homeobox 1 (PROX1). The lymphatic vasculature forms a hierarchical network that consists of blind-ended and unidirectional vessels. Although much progress has been made in the elucidation of the cellular and molecular mechanisms underlying the formation of the lymphatic vascular system, the causes of lymphatic vessel abnormalities and disease are poorly understood and complicated; specifically, the mechanistic basis for transcriptional dysregulation in lymphatic vessel development remains largely unclear. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms of lymphatic vascular development, including LEC differentiation, lymphangiogenesis, and valve formation, and the significance of mechanical forces in lymphatic vessels, with a focus on transcriptional regulation. We also summarize the current knowledge on epigenetic mechanisms of lymphatic gene expression.

show abstract

“…Mafb regulates morphogenesis of a subset of lymphatic beds, including the skin and diaphragm in mice ( Dieterich et al, 2020 ; Rondon-Galeano et al, 2020 ). Mafba and Mafbb, two paralogs in zebrafish, tune the directionality of LEC migration in facial lymphatic development, without affecting cell motility ( Arnold et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

From lymphatic endothelial cell migration to formation of tubular lymphatic vascular network

Shiiya

Hirashima²

2023

Front. Physiol.

View full text Add to dashboard Cite

During development, lymphatic endothelial cell (LEC) progenitors differentiate from venous endothelial cells only in limited regions of the body. Thus, LEC migration and subsequent tube formation are essential processes for the development of tubular lymphatic vascular network throughout the body. In this review, we discuss chemotactic factors, LEC-extracellular matrix interactions and planar cell polarity regulating LEC migration and formation of tubular lymphatic vessels. Insights into molecular mechanisms underlying these processes will help in understanding not only physiological lymphatic vascular development but lymphangiogenesis associated with pathological conditions such as tumors and inflammation.

show abstract

mafba and mafbb differentially regulate lymphatic endothelial cell migration in topographically distinct manners

Cited by 7 publications

References 50 publications

Multiple cis-regulatory elements control prox1a expression in distinct lymphatic vascular beds

Multiple cis-regulatory elements control prox1a expression in distinct lymphatic vascular beds

Mechanical forces in lymphatic vessel development: Focus on transcriptional regulation

From lymphatic endothelial cell migration to formation of tubular lymphatic vascular network

Contact Info

Product

Resources

About