Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity.
Elife
; 122024 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-38180023
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-ß, thereby bridging neuronal fate decision to synaptic connectivity. Expression of a BshDam, specifically in L4, reveals Bsh binding to the DIP-ß 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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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Homeodomínio
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Proteínas de Drosophila
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article