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ISL1-based LIM complexes control Slit2 transcription in developing cranial motor neurons.
Kyung-Tai Kim1, Namhee Kim1, Hwan-Ki Kim2
1School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea.
Scientific Reports
|November 8, 2016
Summary
The ISL1 transcription factor is crucial for cranial branchiomotor neuron development, guiding cell positioning and axon pathfinding. It regulates Slit2 expression, essential for normal motor neuron development and diversity.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- LIM-homeodomain (HD) transcription factors orchestrate neuronal subtype identity.
- The ISL1-LHX3 complex specifies somatic motor (SM) neurons, but LIM code roles in motor neuron diversification remain unclear.
Purpose of the Study:
- To investigate the role of ISL1 in cranial branchiomotor (BM) neuron development.
- To elucidate the mechanisms by which ISL1 controls BM neuron positioning and axon guidance.
Main Methods:
- Analysis of Isl1 mutant mice to assess BM neuron development.
- ChIP-seq and microarray analyses to identify ISL1-regulated genes.
- Reporter assays to confirm ISL1 binding to the Slit2 enhancer.
Main Results:
- ISL1 controls postmitotic BM neuron positioning and peripheral axon pathfinding.
- Isl1 mutation leads to stalled BM neuron migration and aberrant axon guidance.
- Slit2 transcript is significantly reduced in BM neurons of Isl1 mutants.
- ISL1, in combination with LHX3 or LHX4, binds the Slit2 enhancer and drives its expression.
Conclusions:
- Combinatorial LIM codes, involving ISL1 and LHX factors, establish cell-type specificity in motor neurons.
- ISL1-mediated regulation of Slit2 is critical for BM neuron axon development and diversification.
