Related Experiment Video
Updated: May 26, 2025
Analyzing Craniofacial Morphogenesis in Zebrafish Using 4D Confocal Microscopy
Published on: January 30, 2014
Additive effects on craniofacial development upon conditional ablation of PDGFRα and SHP2 in the mouse neural crest
Daniel Fuhr1, Jessica Johnston1, Elliott P Brooks1
1Department of Craniofacial Biology, School of Dental Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Background:
Activity of the receptor tyrosine kinase PDGFRα and the tyrosine phosphatase SHP2 are critical for vertebrate craniofacial development. We sought to determine the effect of SHP2 binding to PDGFRα via phenotypic and biochemical analyses of an allelic series of mouse embryos with combined loss of both proteins in the neural crest lineage.
Results:
We demonstrated that SHP2 preferentially binds PDGFRα/α homodimers among the three PDGFR dimers. Analysis of allelic series mutant embryos revealed increased cell death in the lateral nasal and maxillary processes at E10.5, variably penetrant facial blebbing, facial hemorrhaging, midline clefting and loss of the mandibular region at E13.5, and widespread craniofacial bone and cartilage defects at birth. Further, we showed that loss of SHP2 leads to increased phosphorylation of PDGFRα and the downstream effector Erk1/2 in E10.5 allelic series mutant embryo lysates.
Conclusions:
Together, our findings demonstrate additive effects on craniofacial development upon conditional ablation of PDGFRα and SHP2 in the mouse neural crest lineage and indicate that SHP2 may negatively and positively regulate PDGFRα signaling through distinct mechanisms.
Insights
Loss of SHP2 and PDGFRα in mouse neural crest cells causes craniofacial defects. SHP2
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Platelet-derived growth factor receptor alpha (PDGFRα) and SH2-containing protein tyrosine phosphatase 2 (SHP2) are crucial for craniofacial development.
- The interaction between PDGFRα and SHP2 is essential for normal vertebrate development.
Purpose of the Study:
- To investigate the effects of combined PDGFRα and SHP2 loss in neural crest cells on craniofacial development.
- To analyze the biochemical and phenotypic consequences of SHP2 binding to PDGFRα.
Main Methods:
- Utilized an allelic series of mouse embryos with conditional loss of PDGFRα and SHP2 in neural crest lineage.
- Performed phenotypic and biochemical analyses, including Western blotting and embryo imaging.
Main Results:
- SHP2 preferentially binds PDGFRα homodimers.
- Loss of SHP2 and PDGFRα resulted in increased cell death, facial abnormalities (blebbing, clefting), and craniofacial bone/cartilage defects.
- SHP2 deficiency led to increased PDGFRα and Erk1/2 phosphorylation.
Conclusions:
- Conditional ablation of PDGFRα and SHP2 in mouse neural crest lineage shows additive effects on craniofacial development.
- SHP2 exhibits dual regulation of PDGFRα signaling, acting both negatively and positively through distinct mechanisms.
