PUBLICATION
Tmem88 confines ectodermal Wnt2bb signaling in pharyngeal arch artery progenitors for balancing cell cycle progression and cell fate decision
- Authors
- Zhang, M., Liu, J., Mao, A., Ning, G., Cao, Y., Zhang, W., Wang, Q.
- ID
- ZDB-PUB-250327-31
- Date
- 2023
- Source
- Nature cardiovascular research 2: 234250234-250 (Journal)
- Registered Authors
- Wang, Qiang, Zhang, Wenqing
- Keywords
- none
- MeSH Terms
-
- Gene Expression Regulation, Developmental
- Animals
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Wnt Signaling Pathway/physiology
- Zebrafish*
- Stem Cells/cytology
- Stem Cells/metabolism
- Wnt Proteins/genetics
- Wnt Proteins/metabolism
- Hemangioblasts/cytology
- Hemangioblasts/metabolism
- Animals, Genetically Modified
- Ectoderm/cytology
- Ectoderm/metabolism
- Cell Differentiation*
- Cyclin-Dependent Kinase 4/genetics
- Cyclin-Dependent Kinase 4/metabolism
- Arteries/cytology
- Arteries/metabolism
- Homeobox Protein Nkx-2.5/genetics
- Homeobox Protein Nkx-2.5/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Cyclin D1/genetics
- Cyclin D1/metabolism
- Cell Cycle/physiology
- Cell Proliferation*
- Branchial Region*/cytology
- Branchial Region*/embryology
- Branchial Region*/metabolism
- Cell Lineage
- Cyclin-Dependent Kinase 6/genetics
- Cyclin-Dependent Kinase 6/metabolism
- PubMed
- 39195996 Full text @ Nat Cardiovasc Res
Citation
Zhang, M., Liu, J., Mao, A., Ning, G., Cao, Y., Zhang, W., Wang, Q. (2023) Tmem88 confines ectodermal Wnt2bb signaling in pharyngeal arch artery progenitors for balancing cell cycle progression and cell fate decision. Nature cardiovascular research. 2:234250234-250.
Abstract
Pharyngeal arch artery (PAA) progenitors undergo proliferative expansion and angioblast differentiation to build vessels connecting the heart with the dorsal aortae. However, it remains unclear whether and how these two processes are orchestrated. Here we demonstrate that Tmem88 is required to fine-tune PAA progenitor proliferation and differentiation. Loss of zebrafish tmem88a/b leads to an excessive expansion and a failure of differentiation of PAA progenitors. Moreover, tmem88a/b deficiency enhances cyclin D1 expression in PAA progenitors via aberrant Wnt signal activation. Mechanistically, cyclin D1-CDK4/6 promotes progenitor proliferation through accelerating the G1/S transition while suppressing angioblast differentiation by phosphorylating Nkx2.5/Smad3. Ectodermal Wnt2bb signaling is confined by Tmem88 in PAA progenitors to ensure a balance between proliferation and differentiation. Therefore, the proliferation and angioblast differentiation of PAA progenitors manifest an inverse relationship and are delicately regulated by cell cycle machinery downstream of the Tmem88-Wnt pathway.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping