Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face

Area of Science:

• Developmental Biology
• Molecular Biology
• Cell Biology

Background:

• Fibroblast growth factor (FGF) signaling influences craniofacial development via neural crest cells.
• Previous studies linked increased FGF signaling in the frontonasal process (FNP) to dysmorphology, reduced proliferation, and altered cell orientation.
• RTK signaling's role in craniofacial morphogenesis suggests specific downstream effectors regulate cellular activities.

Purpose of the Study:

• To investigate the roles of three downstream branches of RTK signaling (MEK1/2, PI3K, PLCy) in regulating cellular activities.
• To determine how inhibiting these RTK downstream pathways affects FNP morphogenesis.
• To understand the robustness of RTK signaling in developmental processes.

Main Methods:

• Small molecule inhibitors targeting MEK1/2, PI3K, and PLCy were applied to the chicken embryo FNP.
• Inhibitors were administered individually and in tandem.
• DMSO served as the control treatment.

Main Results:

• All treatments resulted in asymmetric proximodistal truncation of the treated FNP side and mild expansion on the untreated side.
• Inhibition of each pathway led to decreased cell proliferation and disrupted cellular orientation.
• Apoptosis levels remained unaffected by the pathway inhibitions.

Conclusions:

• RTK signaling downstream pathways are robust to developmental perturbation.
• Redundant signaling systems likely contribute to the resilience of craniofacial development.
• Specific RTK effectors are critical for regulating cellular activities during FNP morphogenesis.