Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Oct. 2, 2023

How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina (L1-L5), we show the primary homeodomain transcription factor (HDTF) brain-specific homeobox (Bsh) is initiated in progenitors and maintained L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) Pdm3 (L5) specifies neuronal fates while repressing HDTF Zfh1 prevent ectopic L1/L3 (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating diversity for normal visual sensitivity. Subsequently, L4 neurons, function a feed-forward loop activate synapse recognition molecule DIP-β, bridging fate decision synaptic connectivity. Expression of Bsh:Dam, specifically L4, reveals binding DIP-β locus additional candidate functional identity genes. We propose hierarchically coordinate molecular identity, circuit formation, function. Hierarchical may represent conserved mechanism linking assembly

Language: Английский

Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity

eLife, Journal Year: 2024, Volume and Issue: 12

Published: Jan. 5, 2024

How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina (L1-L5), we show the primary homeodomain transcription factor (HDTF) brain-specific homeobox (Bsh) is initiated in progenitors and maintained L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) Pdm3 (L5) specifies neuronal fates while repressing HDTF Zfh1 prevent ectopic L1/L3 (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating diversity for normal visual sensitivity. Subsequently, L4 neurons, function a feed-forward loop activate synapse recognition molecule DIP-β, bridging fate decision synaptic connectivity. Expression of Bsh:Dam, specifically L4, reveals binding DIP-β locus additional candidate functional identity genes. We propose hierarchically coordinate molecular identity, circuit formation, function. Hierarchical may represent conserved mechanism linking assembly

Language: Английский

Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Oct. 1, 2021

Abstract How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina (L1-L5), we show the primary homeodomain transcription factor (HDTF) Brain-specific homeobox (Bsh) is initiated in progenitors and maintained L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) Pdm3 (L5) specifies neuronal fates while repressing HDTF Zfh1 prevent ectopic L1/L3 (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating diversity for normal visual sensitivity. Subsequently, L4 neurons, function a feed-forward loop activate synapse recognition molecule DIP-β, bridging fate decision synaptic connectivity. Expression of Bsh:Dam, specifically L4, reveals binding DIP-β locus additional candidate functional identity genes. We propose hierarchically coordinate molecular identity, circuit formation, function. Hierarchical may represent conserved mechanism linking assembly

Language: Английский