Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling
- Authors
- Novikov, N., and Evans, T.
- ID
- ZDB-PUB-130816-37
- Date
- 2013
- Source
- Development (Cambridge, England) 140(18): 3787-98 (Journal)
- Registered Authors
- Evans, Todd
- Keywords
- none
- Datasets
- GEO:GSE44026
- MeSH Terms
-
- Mesoderm/drug effects
- Mesoderm/embryology
- Mesoderm/metabolism
- Animals
- Genetic Association Studies
- Mutation/genetics
- Wnt Signaling Pathway*/drug effects
- Wnt Signaling Pathway*/genetics
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Cardiomyopathies/embryology
- Cardiomyopathies/metabolism
- Cardiomyopathies/pathology
- Myocardium/metabolism
- Myocardium/pathology
- Cell Proliferation/drug effects
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Phenotype
- Embryo, Nonmammalian/metabolism
- Down-Regulation/drug effects
- Down-Regulation/genetics
- Organogenesis/drug effects
- Organogenesis/genetics
- Gene Expression Regulation, Developmental/drug effects
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- GATA Transcription Factors/metabolism*
- RNA Transport/genetics
- Body Patterning*/drug effects
- Body Patterning*/genetics
- Stem Cells/cytology
- Stem Cells/drug effects
- Stem Cells/metabolism*
- Cell Lineage/drug effects
- Cell Lineage/genetics
- Morpholinos/pharmacology
- Zebrafish/embryology
- Zebrafish/genetics
- GATA5 Transcription Factor/metabolism*
- Apoptosis/drug effects
- Apoptosis/genetics
- Myocytes, Cardiac/cytology*
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Biomarkers/metabolism
- PubMed
- 23903195 Full text @ Development
Biphasic control of WNT signaling is essential during cardiogenesis, but how the pathway switches from promoting cardiac mesoderm to restricting cardiomyocyte progenitor fate is unknown. We identified genes expressed in lateral mesoderm that are dysregulated in zebrafish when both gata5 and gata6 are depleted, causing a block to cardiomyocyte specification. This screen identified tmem88a, which is expressed in the early cardiac progenitor field and was previously implicated in WNT modulation by overexpression studies. Depletion of tmem88a results in a profound cardiomyopathy, secondary to impaired cardiomyocyte specification. In tmem88a morphants, activation of the WNT pathway exacerbates the cardiomyocyte deficiency, whereas WNT inhibition rescues progenitor cells and cardiogenesis. We conclude that specification of cardiac fate downstream of gata5/6 involves activation of the tmem88a gene to constrain WNT signaling and expand the number of cardiac progenitors. Tmem88a is a novel component of the regulatory mechanism controlling the second phase of biphasic WNT activity essential for embryonic cardiogenesis.