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Series GSE246726 Query DataSets for GSE246726
Status Public on Nov 05, 2023
Title Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity
Organism Drosophila melanogaster
Experiment type Other
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.
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.
Web link
Contributor(s) Xu C, Ramos TB, Rogers EM, Reiser MB, Doe CQ
Citation(s) 38180023
BioProject PRJNA1033781
Submission date Nov 01, 2023
Last update date Feb 04, 2024
Contact name Chris Doe
Organization name University of Oregon
Street address 1440 Franklin Blvd
City Eugene
ZIP/Postal code 97403
Country USA
Platforms (1)
GPL25244 Illumina NovaSeq 6000 (Drosophila melanogaster)
Samples (3)
GSM7876066 L4-Bsh-Dam, rep1
GSM7876067 L4-Bsh-Dam, rep2
GSM7876068 L4-Bsh-Dam, rep3

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Supplementary file Size Download File type/resource
GSE246726_RAW.tar 14.5 Mb (http)(custom) TAR (of BEDGRAPH, CSV, GFF)
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Raw data are available in SRA

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