Regulation of otic neurosensory specification by Notch and Wnt signalling: insights from RNA-seq screenings in the...

Area of Science:

• Developmental Biology
• Cell Signaling
• Genomics

Background:

• Notch and Wnt signaling pathways are crucial for inner ear sensory organ formation.
• Transcriptional effectors and targets of these pathways in the developing inner ear remain largely uncharacterized.

Purpose of the Study:

• To elucidate the transcriptional targets and effectors of Notch and Wnt signaling during embryonic inner ear development.
• To investigate the robustness of endogenous neurosensory specification programs.

Main Methods:

• Perturbation of Notch and Wnt signaling in embryonic chicken otic vesicles via pharmacological treatment and in ovo electroporation.
• RNA-sequencing (RNA-Seq) was employed to analyze gene expression changes.
• Preliminary gain-of-function screening of transcription factors and Wnt signaling components.

Main Results:

• Pharmacological Notch inhibition rapidly altered gene expression, promoting a neurosensory fate.
• Wnt pathway activation identified numerous genes linked to neurosensory function.
• In ovo electroporation resulted in fewer gene expression changes compared to pharmacological methods due to transfection variability.
• Overexpression of single factors generally did not affect endogenous neurosensory specification programs, indicating robustness.

Conclusions:

• This research provides novel insights into the effectors and candidate targets of Notch and Wnt pathways in the developing avian inner ear.
• The findings offer a valuable reference for future functional genomics studies in this model system.
• The study highlights the significant role of Wnt signaling in neurosensory specification within the otocyst.