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| Status |
Public on Nov 05, 2023 |
| Title |
Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity |
| Organism |
Drosophila melanogaster |
| Experiment type |
Other
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| Summary |
How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina neuron types (L1-L5), we show that the primary homeodomain transcription factor (HDTF) Brain-specific homeobox (Bsh) is initiated in progenitors and maintained in L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates while repressing the HDTF Zfh1 to prevent ectopic L1/L3 fates (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating lamina neuronal diversity for normal visual sensitivity. Subsequently, in L4 neurons, Bsh and Ap function in a feed-forward loop to activate the synapse recognition molecule DIP-β, thereby bridging neuronal fate decision to synaptic connectivity. Expression of a Bsh:Dam specifically in L4 reveals Bsh binding to the DIP-β locus and additional candidate L4 functional identity genes. We propose that HDTFs function hierarchically to coordinate neuronal molecular identity, circuit formation, and function. Hierarchical HDTFs may represent a conserved mechanism for linking neuronal diversity to circuit assembly and function.
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| Overall design |
In C. elegans, terminal selectors show non-redundant control of neuronal identity genes and redundant control of pan-neuronal genes. To see if the same mechanism is used by the HDTF Bsh, we profiled Bsh direct targets with precise spatial and temporal control: only in L4 neurons at the time of synapse formation (46-76h APF). To do this, we used Targeted DamID (Aughey et al., 2021), which can be used to identify Bsh DNA-binding sites across the genome.
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| Web link |
https://elifesciences.org/articles/90133
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| Contributor(s) |
Xu C, Ramos TB, Rogers EM, Reiser MB, Doe CQ |
| Citation(s) |
38180023 |
| BioProject |
PRJNA1033781 |
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| Submission date |
Nov 01, 2023 |
| Last update date |
Feb 04, 2024 |
| Contact name |
Chris Doe |
| E-mail(s) |
cdoe@uoregon.edu
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| Organization name |
University of Oregon
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| Street address |
1440 Franklin Blvd
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| City |
Eugene |
| ZIP/Postal code |
97403 |
| Country |
USA |
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| Platforms (1) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
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| Samples (3) |
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| Supplementary file |
Size |
Download |
File type/resource |
| GSE246726_RAW.tar |
14.5 Mb |
(http)(custom) |
TAR (of BEDGRAPH, CSV, GFF) |
SRA Run Selector |
| Raw data are available in SRA |
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