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hkb is required for DIP-α expression and target recognition in the Drosophila neuromuscular circuit
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hkb is required for DIP-α expression and target recognition in the Drosophila neuromuscular circuit
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Journal Article
hkb is required for DIP-α expression and target recognition in the Drosophila neuromuscular circuit
2024
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 14/19
/ 14/35
/ 38/47
/ 64/24
/ Animals
/ Biomedical and Life Sciences
/ Drosophila melanogaster - genetics
/ Drosophila melanogaster - metabolism
/ Drosophila Proteins - genetics
/ Drosophila Proteins - metabolism
/ Insects
/ Neuromuscular Junction - genetics
/ Neuromuscular Junction - metabolism
/ Neurons
