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Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity.

ABSTRACT: 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.

SUBMITTER: Xu C

PROVIDER: S-EPMC10942767 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity.

Xu Chundi C Ramos Tyler B TB Rogers Edward M EM Reiser Michael B MB Doe Chris Q CQ

eLife 20240105

How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using <i>Drosophila</i> 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-kno ...[more]

PMID: 38180023

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Dataset Information

Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity.

Publications

Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity.

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