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| Status |
Public on Aug 02, 2019 |
| Title |
Lmx1b is required at multiple stages to build expansive serotonergic axon architectures |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Formation of long-range axons occurs over multiple stages of morphological maturation. However, the intrinsic transcriptional mechanisms that temporally control different stages of axon projection development are unknown. Here, we addressed this question by studying the formation of mouse serotonin (5-HT) axons, the exemplar of long-range profusely arborized axon architectures. We report that LIM homeodomain factor 1b (Lmx1b)-deficient 5-HT neurons fail to generate axonal projections to the forebrain and spinal cord. Stage-specific targeting demonstrates that Lmx1b is required at successive stages to control 5-HT axon primary outgrowth, selective routing, and terminal arborization. We show a Lmx1b→Pet1 regulatory cascade is temporally required for 5-HT arborization and upregulation of the 5-HT axon arborization gene, Protocadherin-alphac2, during postnatal development of forebrain 5-HT axons. Our findings identify a temporal regulatory mechanism in which a single continuously expressed transcription factor functions at successive stages to orchestrate the progressive development of long-range axon architectures enabling expansive neuromodulation.
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| Overall design |
5-HT neuron RNA profiles of control (CON), Lmx1bCKO, and Pet1CKO (at E17.5 and P2 (Lmx1bCKO only at P2)) mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 500/550. The sequence reads that passed quality filters were analyzed at the gene level with TopHat2 followed by Cufflinks.
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| Contributor(s) |
Donovan LJ, Spencer WC, Kitt M, Eastman B, Lobur KJ, Silver J, Jiao K, Deneris ES |
| Citation(s) |
31355748 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P50 MH096972 |
Early Brain Serotonin and Its Lasting Impact on Neuronal Epigenetic Programming |
CASE WESTERN RESERVE UNIVERSITY |
EVAN S DENERIS |
| R01 MH062723 |
genetic mechanisms controlling serotonergic function across life span |
CASE WESTERN RESERVE UNIVERSITY |
EVAN S DENERIS |
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| Submission date |
Apr 30, 2019 |
| Last update date |
Aug 02, 2019 |
| Contact name |
Evan Deneris |
| E-mail(s) |
esd@case.edu
|
| Organization name |
Case Western Reserve University
|
| Department |
Neurosciences
|
| Street address |
2109 Adelbert Rd.
|
| City |
Cleveland |
| State/province |
OH |
| ZIP/Postal code |
44106 |
| Country |
USA |
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| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL21626 |
NextSeq 550 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA540504 |
| SRA |
SRP194283 |
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