Interlocked transcription factor feedback loops maintain and restore touch sensation

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• The sense of touch depends on mechanosensory circuits, but the molecular basis for their continuous function is unclear.
• Understanding how neuronal identity is maintained in adults is crucial for circuit stability.

Purpose of the Study:

• To investigate the molecular mechanisms maintaining adult mechanosensory neuron identity and function.
• To identify transcription factors involved in adult neuronal circuit stability.

Main Methods:

• Utilized C. elegans as a model organism.
• Manipulated levels of transcription factors CFI-1 (ARID3) and EGL-5 (HOXA7) in adult animals.
• Assessed touch-evoked escape response and interneuron molecular identity.

Main Results:

• CFI-1 and EGL-5 jointly maintain the identity of key interneurons in adult C. elegans.
• Altering CFI-1 or EGL-5 levels caused digital-like (ON/OFF) changes in escape response and interneuron identity.
• Restoring CFI-1 levels reversed adult-onset touch response defects.
• Identified a CFI-1/EGL-5 feedback loop and CFI-1 autoregulation that lock in neuronal identity.

Conclusions:

• A regulatory network involving CFI-1 and EGL-5 maintains adult neuron identity and robust mechanosensory circuit function.
• This network is essential for the restorability of adult-onset neuronal and behavioral defects.
• Findings provide insights into maintaining neuronal function and potential therapeutic strategies for neurological disorders.