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Tmem2 restricts atrioventricular canal differentiation by regulating degradation of hyaluronic acid.
- Source :
-
Developmental dynamics : an official publication of the American Association of Anatomists [Dev Dyn] 2019 Dec; Vol. 248 (12), pp. 1195-1210. Date of Electronic Publication: 2019 Sep 10. - Publication Year :
- 2019
-
Abstract
- Background: Atrioventricular valve development relies upon the precisely defined dimensions of the atrioventricular canal (AVC). Current models suggest that Wnt signaling plays an important role atop a pathway that promotes AVC development. The factors that confine AVC differentiation to the appropriate location, however, are less well understood.<br />Results: Transmembrane protein 2 (Tmem2) is a key player in restricting AVC differentiation: in zebrafish, tmem2 mutants display an expansion of AVC characteristics, but the molecular mechanism of Tmem2 function in this context remains unclear. Through structure-function analysis, we demonstrate that the extracellular portion of Tmem2 is crucial for its role in restricting AVC boundaries. Importantly, the Tmem2 ectodomain contains regions implicated in the depolymerization of hyaluronic acid (HA). We find that tmem2 mutant hearts exhibit excess HA deposition alongside broadened distribution of Wnt signaling. Moreover, addition of ectopic hyaluronidase can restore the restriction of AVC differentiation in tmem2 mutants. Finally, we show that alteration of a residue important for HA depolymerization impairs the efficacy of Tmem2 function during AVC development.<br />Conclusions: Taken together, our data support a model in which HA degradation, regulated by Tmem2, limits the distribution of Wnt signaling and thereby confines the differentiation of the AVC.<br /> (© 2019 Wiley Periodicals, Inc.)
- Subjects :
- Animals
Animals, Genetically Modified
Carbohydrate Metabolism genetics
Embryo, Nonmammalian
Heart embryology
Heart Septal Defects metabolism
Membrane Proteins genetics
Membrane Proteins metabolism
Organogenesis genetics
Signal Transduction genetics
Wnt Signaling Pathway genetics
Zebrafish embryology
Zebrafish genetics
Zebrafish Proteins genetics
Zebrafish Proteins metabolism
Heart Septal Defects genetics
Heart Septum embryology
Heart Ventricles embryology
Hyaluronic Acid metabolism
Membrane Proteins physiology
Zebrafish Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0177
- Volume :
- 248
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Developmental dynamics : an official publication of the American Association of Anatomists
- Publication Type :
- Academic Journal
- Accession number :
- 31444829
- Full Text :
- https://doi.org/10.1002/dvdy.106