# Src/Fas2-dependent Ephrin phosphorylation initiates Eph/Ephrin reverse signaling through Rac1 to shape columnar units in the fly brain

## TL;DR

This study reveals how Ephrin signaling, with the help of Src/Fas2 and Rac1, shapes columnar units in the fly brain.

## Contribution

The study identifies a novel Ephrin/Src/Fas2/Rac1 signaling pathway involved in column formation in the fly brain.

## Key findings

- Ephrin and Eph regulate columnar neuron morphology and location through bidirectional signaling.
- Eph ligand triggers Ephrin phosphorylation via Src/Fas2 to promote reverse signaling through Rac1.
- The Ephrin/Src/Fas2 complex is essential for reverse signaling in column formation.

## Abstract

Columns are the morphological and functional units containing multiple neurons in the brain. The molecular mechanisms of column formation are largely unknown. Ephrin/Eph signaling mediates a variety of developmental processes. Ephrin acts as a ligand for Eph to regulate forward signaling, whereas Eph acts as a ligand for Ephrin to regulate reverse signaling. However, whether and how the uni- or bidirectional Ephrin/Eph signaling is involved in column formation remains elusive. In this study, we show that Ephrin and Eph regulate the morphology and location of columnar neurons through bidirectional repulsive signaling. Furthermore, Eph ligand triggers cytoplasmic tyrosine phosphorylation of Ephrin under the control of Src kinases and Fasciclin 2 (Fas2), forming the Ephrin/Src/Fas2 complex to promote reverse signaling through a downstream regulator, Rac1. This study provides the detailed analysis of the molecular interactions involved in column formation using the fly brain as a model.

Reverse Ephrin signaling drives fly brain column formation—mechanistic link via Src/Fas2-Rac1.