PUBLICATION
The mediator complex subunit Med10 regulates heart valve formation in zebrafish by controlling Tbx2b-mediated Has2 expression and cardiac jelly formation
- Authors
- Just, S., Hirth, S., Berger, I.M., Fishman, M.C., Rottbauer, W.
- ID
- ZDB-PUB-160628-12
- Date
- 2016
- Source
- Biochemical and Biophysical Research Communications 477(4): 581-8 (Journal)
- Registered Authors
- Berger, Ina, Fishman, Mark C., Hirth, Sophia, Just, Steffen, Rottbauer, Wolfgang
- Keywords
- Foxn4, Has2, Med10, Tbx2b, Valve formation, Zebrafish
- MeSH Terms
-
- Zebrafish Proteins/metabolism*
- Zebrafish Proteins/physiology*
- T-Box Domain Proteins/metabolism
- T-Box Domain Proteins/physiology*
- Forkhead Transcription Factors/metabolism
- Signal Transduction
- Mutation
- Heart Valves/embryology*
- Heart Valves/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics
- Animals
- Mediator Complex/physiology*
- Glucuronosyltransferase/metabolism*
- PubMed
- 27343557 Full text @ Biochem. Biophys. Res. Commun.
Citation
Just, S., Hirth, S., Berger, I.M., Fishman, M.C., Rottbauer, W. (2016) The mediator complex subunit Med10 regulates heart valve formation in zebrafish by controlling Tbx2b-mediated Has2 expression and cardiac jelly formation. Biochemical and Biophysical Research Communications. 477(4):581-8.
Abstract
In search for novel key regulators of cardiac valve formation, we isolated the zebrafish cardiac valve mutant ping pong (png). We find that an insertional promoter mutation within the zebrafish mediator complex subunit 10 (med10) gene is leading to impaired heart valve formation. Expression of the T-box transcription factor 2b (Tbx2b), known to be essential in cardiac valve development, is severely reduced in png mutant hearts. We demonstrate here that transient reconstitution of Tbx2b expression rescues AV canal development in png mutant zebrafish. By contrast, overexpression of Forkhead box N4 (Foxn4), a known upstream regulator of Tbx2b, is not capable to reconstitute tbx2b expression and heart valve formation in Med10-deficient png mutant hearts. Interestingly, hyaluronan synthase 2 (has2), a known downstream target of Tbx2 and producer of hyaluronan (HA) - a major ECM component of the cardiac jelly and critical for proper heart valve development - is completely absent in ping pong mutant hearts. We propose here a rather unique role of Med10 in orchestrating cardiac valve formation by mediating Foxn4 dependent tbx2b transcription, the expression of Has2 and subsequently the proper development of the cardiac jelly.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping