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Updated: Jul 8, 2026
En Face Endocardial Cushion Preparation for Planar Morphogenesis Analysis in Mouse Embryos
Published on: July 27, 2022
PDGF-B signaling is important for murine cardiac development: its role in developing atrioventricular valves,
Nynke M S Van den Akker1, Leah C J Winkel, Maya H Nisancioglu
1Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Platelet-derived growth factor (PDGF)-B/PDGFR-beta signaling is crucial for heart development, impacting epicardium-derived cells and cardiac neural crest contributions. Its absence causes significant cardiac structural defects and impaired innervation.
Area of Science:
- Developmental Biology
- Cardiovascular Research
- Cell Signaling
Background:
- Epicardium-derived cells and cardiac neural crest are vital for heart development.
- Platelet-derived growth factor (PDGF)-B/PDGFR-beta signaling pathways are implicated in various developmental processes.
- The specific role of PDGF-B/PDGFR-beta in the contribution of these cell lineages to cardiac development requires elucidation.
Purpose of the Study:
- To investigate the role of PDGF-B/PDGFR-beta signaling in the cardiac contribution of epicardium-derived cells and cardiac neural crest.
- To analyze structural cardiac aberrations in mouse models with defective PDGF-B or PDGFR-beta signaling.
Main Methods:
- Analysis of embryonic hearts from Pdgf-b-/- and Pdgfr-beta-/- mouse embryos at different developmental stages.
- Immunohistochemical staining for key developmental markers including alphaSMA, periostin, ephrinB2, EphB4, VEGFR-2, Dll1, and NCAM.
- Comparison of knockout embryos with wild-type controls to identify structural abnormalities.
Main Results:
- Knockout embryos exhibited perimembranous and muscular ventricular septal defects.
- Maldevelopment of atrioventricular cushions and valves was observed.
- Impaired coronary arteriogenesis and hypoplasia of the myocardium and cardiac nerves were noted.
- These defects align with impaired epicardial development and neural crest-related innervation deficits.
Conclusions:
- PDGF-B/PDGFR-beta signaling plays a critical role in the contribution of epicardium-derived cells and cardiac neural crest to heart development.
- Defects in this signaling pathway lead to a spectrum of congenital heart abnormalities.
- This study highlights the specific importance of PDGF-B/PDGFR-beta in cardiac morphogenesis and innervation.
Abstract:
We hypothesized that PDGF-B/PDGFR-beta-signaling is important in the cardiac contribution of epicardium-derived cells and cardiac neural crest, cell lineages crucial for heart development. We analyzed hearts of different embryonic stages of both Pdgf-b-/- and Pdgfr-beta-/- mouse embryos for structural aberrations with an established causal relation to defective contribution of these cell lineages. Immunohistochemical staining for alphaSMA, periostin, ephrinB2, EphB4, VEGFR-2, Dll1, and NCAM was performed on wild-type and knockout embryos. We observed that knockout embryos showed perimembranous and muscular ventricular septal defects, maldevelopment of the atrioventricular cushions and valves, impaired coronary arteriogenesis, and hypoplasia of the myocardium and cardiac nerves. The abnormalities correspond with models in which epicardial development is impaired and with neuronal neural crest-related innervation deficits. This implies a role for PDGF-B/PDGFR-beta-signaling specifically in the contribution of these cell lineages to cardiac development.
