Barcoding Notch signaling in the developing brain

Area of Science:

• Developmental Biology
• Genomics
• Neuroscience

Background:

• Developmental signaling pathways are crucial for cell fate determination and behavior.
• Traditional reporters like fluorescent proteins have limitations in scalability and cell-type resolution.
• A need exists for precise methods to track dynamic signaling events in developing tissues.

Approach:

• We developed SABER-seq, a CRISPR-Cas based molecular recorder system.
• SABER-seq captures transient signaling cues as permanent genomic mutations.
• This system combines a signaling sensor with a barcode recorder for inducible Notch signaling tracking.

Key Points:

• SABER-seq was applied to map Notch signaling in developing zebrafish brains.
• The system allows deconstruction of signaling history via single-cell transcriptomics.
• Identified cell types influenced by Notch signaling and potential differential impacts on terminal fates.

Conclusions:

• SABER-seq provides a novel platform for scalable, high-resolution mapping of developmental signaling.
• This technology enhances our understanding of cell fate decisions driven by signaling pathways.
• Enables detailed analysis of signaling dynamics in complex biological systems.