# hkb is required for DIP-α expression and target recognition in the Drosophila neuromuscular circuit

## TL;DR

This study identifies hkb as a key regulator of DIP-α expression in Drosophila motor neurons, revealing how transcription factors control synaptic connectivity.

## Contribution

The paper discovers that hkb regulates DIP-α expression specifically in dorsal Is motor neurons through interaction with even-skipped.

## Key findings

- hkb is required for DIP-α expression in dorsal Is motor neurons.
- even-skipped acts downstream of hkb to specify DIP-α expression in these neurons.
- hkb and even-skipped function in the same pathway to regulate synaptic connectivity.

## Abstract

Our nervous system contains billions of neurons that form precise connections with each other through interactions between cell surface proteins. In Drosophila, the Dpr and DIP immunoglobulin protein subfamilies form homophilic or heterophilic interactions to instruct synaptic connectivity, synaptic growth, and cell survival. However, the upstream regulatory mechanisms of Dprs and DIPs are not clear. On the other hand, while transcription factors have been implicated in target recognition, their downstream cell surface proteins remain mostly unknown. We conduct an F1 dominant modifier genetic screen to identify regulators of Dprs and DIPs. We identify huckebein (hkb), a transcription factor previously implicated in target recognition of the dorsal Is motor neuron. We show that hkb genetically interacts with DIP-α and loss of hkb leads to complete removal of DIP-α expression specifically in dorsal Is motor neurons. We then confirm that this specificity is through the dorsal Is motor neuron specific transcription factor, even-skipped (eve), which acts downstream of hkb. Analysis of the genetic interaction between hkb and eve reveals that they act in the same pathway to regulate dorsal Is motor neuron connectivity. Our study provides insight into the transcriptional regulation of DIP-α and suggests that distinct regulatory mechanisms exist for the same CSP in different neurons.

A dominate modifier screen in Drosophila identifies transcriptional regulators that control expression of DIP-α, a cell surface protein, and synaptic target recognition in the neuromuscular system.