MAFB modulates the maturation of lymphatic vascular networks in mice

MAFB modulates the maturation of lymphatic vascular networks in mice.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1002/dvdy.209
Journal or Publication Title: Developmental Dynamics
Volume: 249
Number: 10
Page Range: pp. 1201-1216
Date: 2020
Divisions: David Richmond program for Cardiovascular Development
Depositing User: General Admin
Identification Number: 10.1002/dvdy.209
ISSN: 1058-8388
Date Deposited: 04 Jan 2021 04:04
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 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.

Creators:
Creators
Email
Rondon‐Galeano, Maria
UNSPECIFIED
Skoczylas, Renae
UNSPECIFIED
Bower, Neil I.
UNSPECIFIED
Simons, Cas
UNSPECIFIED
Gordon, Emma
UNSPECIFIED
Francois, Mathias
UNSPECIFIED
Koltowska, Katarzyna
UNSPECIFIED
Hogan, Benjamin M.
UNSPECIFIED
Last Modified: 04 Jan 2021 04:04
URI: https://eprints.centenary.org.au/id/eprint/727

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