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Published on: April 18, 2017
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Sox11 genes affect neuronal differentiation in the developing zebrafish enteric nervous system.
Yuanyun Huang1, Can Li1, Ayyappa Raja Desingu Rajan1
1Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Summary
Sox11a and Sox11b are crucial for specifying neuronal subtypes in the developing zebrafish enteric nervous system (ENS). Their depletion reduces inhibitory motor neuron numbers by affecting enhancer activity.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- The vertebrate enteric nervous system (ENS) originates from vagal neural crest cells.
- These cells migrate to populate the entire gut, differentiating into various neuronal subtypes.
Purpose of the Study:
- To investigate the role of transcription factors sox11a and sox11b in zebrafish ENS development.
- To understand how sox11 paralogs influence neuronal subtype specification.
Main Methods:
- CRISPR-Cas9 gene depletion to study loss-of-function effects.
- ATAC-seq and transcription factor footprinting to identify Sox11 binding sites.
- Reporter gene assays with mutational analysis to confirm enhancer function.
Main Results:
- Sox11a and Sox11b are highly expressed in transitioning neural crest cells.
- Loss of sox11 paralogs decreases the number of adcyap1b-expressing inhibitory motor neurons.
- Sox11 binding sites were identified in the adcyap1b enhancer and are essential for its activity.
Conclusions:
- Sox11a and Sox11b play a critical, previously unrecognized role in specifying inhibitory motor neuron subtypes within the developing zebrafish ENS.
- These transcription factors regulate neuronal differentiation through enhancer elements like the one in adcyap1b.
