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| Status |
Public on Jun 13, 2014 |
| Title |
Transcription Factor Network Specifying Inhibitory versus Excitatory Neurons in the Dorsal Spinal Cord [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification.
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| Overall design |
Examination of gene expression in Ascl1 and Ptf1a lineage cells in the developing neural tube.
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| Contributor(s) |
Borromeo MD, Meredith DM, Castro DS, Chang JC, Tung K, Guillemot F, Johnson JE |
| Citation(s) |
24924197 |
| |
| Submission date |
Mar 12, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Jane E Johnson |
| E-mail(s) |
jane.johnson@utsouthwestern.edu
|
| Organization name |
UT Southwestern Medical Center
|
| Department |
Neuroscience
|
| Street address |
5323 Harry Hines Blvd
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9111 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
|
| Samples (7)
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| This SubSeries is part of SuperSeries: |
| GSE55841 |
Transcription Factor Network Specifying Inhibitory versus Excitatory Neurons in the Dorsal Spinal Cord |
|
| Relations |
| BioProject |
PRJNA241104 |
| SRA |
SRP040010 |
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