PUBLICATION
MAFB modulates the maturation of lymphatic vascular networks in mice
- Authors
- Rondon-Galeano, M., Skoczylas, R., Bower, N.I., Simons, C., Gordon, E., Francois, M., Koltowska, K., Hogan, B.M.
- ID
- ZDB-PUB-200612-12
- Date
- 2020
- Source
- Developmental Dynamics : an official publication of the American Association of Anatomists 249(10): 1201-1216 (Journal)
- Registered Authors
- Hogan, Ben M.
- Keywords
- MAFB, development, lymphangiogenesis, lymphatic, vascular
- MeSH Terms
-
- Animals
- CRISPR-Cas Systems
- Crosses, Genetic
- Genome
- Genotype
- In Situ Hybridization
- Lymphangiogenesis/physiology*
- Lymphatic Vessels/metabolism*
- MafB Transcription Factor/physiology*
- Mice
- Mice, Knockout
- Mutation
- RNA, Messenger/metabolism
- Signal Transduction
- Time Factors
- PubMed
- 32525258 Full text @ Dev. Dyn.
Citation
Rondon-Galeano, M., Skoczylas, R., Bower, N.I., Simons, C., Gordon, E., Francois, M., Koltowska, K., Hogan, B.M. (2020) MAFB modulates the maturation of lymphatic vascular networks in mice. Developmental Dynamics : an official publication of the American Association of Anatomists. 249(10):1201-1216.
Abstract
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 co-ordinated 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 signalling 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. Mafb mutant lymphatics were normal during initial LEC differentiation and sprouting. However, 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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping