The transcription factor LAG-1/CSL plays a Notch-independent role in controlling terminal differentiation, fate...

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Signal-regulated transcription factors (TFs) typically shift from repression to activation during development.
• Terminal selector TFs establish and maintain neuron-type specific gene expression.
• C. elegans has three serotonin-producing neuron types with shared pathway genes but distinct effector genes.

Purpose of the Study:

• To investigate the role of LAG-1, a Notch pathway TF, in the specification of serotonergic neurons in C. elegans.
• To determine if LAG-1 functions as a terminal selector TF for specific serotonergic neuron types.

Main Methods:

• Analysis of LAG-1 binding sites in ADF effector genes.
• Mutant analysis of lag-1 in C. elegans.
• Assessment of Notch signaling independence for LAG-1 function.

Main Results:

• LAG-1 functions as a terminal selector for the ADF serotonergic neuron, not other types.
• Functional LAG-1 binding sites in ADF effector genes mediate activation, not basal repression.
• lag-1 mutants exhibit defects in ADF effector gene activation and cell fate maintenance.
• LAG-1 activates ADF neuron gene expression independently of Notch signaling, showing a default activator state.

Conclusions:

• LAG-1 acts as a terminal selector TF for the ADF neuron, independent of Notch signaling.
• This uncoupled activating role allows for enduring target gene activity essential for maintaining cell fate and function.