Castor specifies NB5-2 late-born interneuron molecular identity and premotor connectivity

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Sensory-motor integration relies on precise interneuron connectivity within the central nervous system (CNS).
• Interneuron identity, determined by transcription factors (TFs) and connectivity, is vital for neural circuit assembly.
• In Drosophila, temporal transcription factor (TTF) cascades in neural progenitors (neuroblasts; NBs) dictate neuron identity, with roles of late TTFs remaining understudied.

Purpose of the Study:

• To investigate the role of the late TTF Castor in specifying the molecular identity and connectivity of late-born interneurons.
• To analyze the function of Castor in the NB5-2 lineage, which produces interneurons contributing to the proprioceptive circuit.

Main Methods:

• Utilized Drosophila melanogaster as a model organism.
• Employed lineage tracing and genetic manipulation (misexpression) in the NB5-2 lineage.
• Analyzed TF expression patterns (Pdm, Grh, Runt, Nab) in progeny.
• Examined synaptic localization and number in specific interneurons (SA1).
• Assessed proprioceptive circuit behavior.

Main Results:

• NB5-2 Castor regulates the temporal expression of Pdm and Grh in progenitors.
• Misexpression of Castor in NB5-2 leads to increased expression of late-born TFs Runt and Nab.
• Identified SA1, SA3, and JA3 as Castor-expressing progeny.
• Observed increased presynapse number in SA1 subregions upon Castor misexpression.
• Demonstrated disruption of proprioceptive circuit behavior.

Conclusions:

• Castor is essential for specifying the molecular identity of late-born interneurons in the NB5-2 lineage.
• Castor influences the connectivity of these interneurons, impacting synaptic organization.
• Castor activity is critical for proper proprioceptive circuit function.