Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo

Bowles, Josephine, Secker, Genevieve, Nguyen, Christelle, Kazenwadel, Jan, Truong, Vy, Framptom, Emmanuelle, Curtis, Cameron, Skoczylas, Renae, Davidson, Tara-Lynn, Miura, Naoyuki, Hong, Young-Kwon, Koopman, Peter, Harvey, Natasha L. and François, Mathias (2014) Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo. Developmental Biology, 386 1: 25-33. doi:10.1016/j.ydbio.2013.12.008

Author Bowles, Josephine
Secker, Genevieve
Nguyen, Christelle
Kazenwadel, Jan
Truong, Vy
Framptom, Emmanuelle
Curtis, Cameron
Skoczylas, Renae
Davidson, Tara-Lynn
Miura, Naoyuki
Hong, Young-Kwon
Koopman, Peter
Harvey, Natasha L.
François, Mathias
Title Control of retinoid levels by CYP26B1 is important for lymphatic vascular development in the mouse embryo
Journal name Developmental Biology   Check publisher's open access policy
ISSN 0012-1606
Publication date 2014-01-02
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.ydbio.2013.12.008
Open Access Status Not Open Access
Volume 386
Issue 1
Start page 25
End page 33
Total pages 9
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Formatted abstract
• Retinoic acid is a molecular cue essential to the patterning the lymphatic vasculature.
• Lymphatic precursor cell express CYP26B1, a retinoic acid catabolic enzyme.
• The number of lymphatic progenitors increases in presence of elevated RA (Cyp26b1-/-).
• Lymphovenous valve malformations occurs in presence of elevated RA (Cyp26b1-/-).
• Hyperplastic, blood filled lymph sacs and lymphatic vessels is due to elevated RA.

During embryogenesis, lymphatic endothelial progenitor cells first arise from a subset of blood vascular endothelial cells in the dorsolateral aspects of the cardinal veins. The molecular cues responsible for defining the regionalisation of such a discrete pool of progenitors remain uncharacterised. Here we identify a novel function for CYP26B1, an enzyme known to play a role in tissue morphogenesis by fine-tuning retinoic acid (RA) concentration, in regulating lymphangiogenesis. Cyp26b1-null mice, in which RA levels are elevated, exhibited an increased number of lymphatic endothelial progenitor cells in the cardinal veins, together with hyperplastic, blood filled lymph sacs and hyperplastic dermal lymphatic vessels. Conversely, mice over-expressing Cyp26b1 had hypoplastic lymph sacs and lymphatic vessels. Our data suggest that RA clearance by CYP26B1 in the vicinity of lymphatic endothelial progenitor cells is important for determining the position and size of the progenitor pool specified. Our studies identify a genetic pathway that underpins the architecture of the developing lymphatics and define CYP26B1 as a novel modulator of lymphatic vascular patterning.
Keyword Prox1
Lymphatic endothelial cells
Retinoic acid
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 19 December 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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Created: Fri, 17 Jan 2014, 07:06:09 EST by Dr Mathias Francois on behalf of Institute for Molecular Bioscience