Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity DOI Open Access
Chundi Xu,

Tyler B. Ramos,

Edward M. Rogers

et al.

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

Determinants of motor neuron functional subtypes important for locomotor speed DOI Creative Commons
Kristen P. D’Elia, Hanna Hameedy, Dena Goldblatt

et al.

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113049 - 113049

Published: Sept. 1, 2023

Locomotion requires precise control of the strength and speed muscle contraction is achieved by recruiting functionally distinct subtypes motor neurons (MNs). MNs are essential to movement differentially susceptible in disease, but little known about how acquire functional subtype-specific features during development. Using single-cell RNA profiling embryonic larval zebrafish, we identify novel conserved molecular signatures for MN genes expressed both early post-mitotic mature MNs. Assessing development genetic mutants, define a program subtype specification. Two evolutionarily transcription factors, Prdm16 Mecom, determinants integral fast Loss prdm16 or mecom causes develop transcriptional profiles innervation similar slow These results reveal diversity vertebrate axial demonstrate that specified through intrinsic codes.

Language: Английский

Citations

31

Temporal and Notch identity determine layer targeting and synapse location of medulla neurons DOI Creative Commons
Isabel Holguera, Yee‐Chun Chen, Yu‐Chieh Chen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

How specification mechanisms that generate neural diversity translate into specific neuronal targeting, connectivity, and function in the adult brain is not understood. In medulla region of Drosophila optic lobe, progenitors different neurons a fixed order by sequentially expressing series temporal transcription factors as they age. Then, Notch signaling intermediate further diversifies progeny. By establishing birth neurons, we found their identity correlates with depth neuropil targeting brain, for both local interneurons projection neurons. We show this identity-dependent unfolds early development genetically determined. leveraging Electron Microscopy reconstruction fly determined synapse location lobe neuropils find it significantly associated status. Moreover, all putative same predicted share similar location, indicating ensembles layers encode visual functions. conclusion, status can predict function, linking developmental patterning connectivity functional features brain.

Language: Английский

Citations

1

Comparative single-cell transcriptomic atlases of drosophilid brains suggest glial evolution during ecological adaptation DOI Creative Commons
Daehan Lee, Michael P. Shahandeh,

Liliane Abuin

et al.

PLoS Biology, Journal Year: 2025, Volume and Issue: 23(4), P. e3003120 - e3003120

Published: April 29, 2025

To explore how brains change upon species evolution, we generated single-cell transcriptomic atlases of the central three closely related but ecologically distinct drosophilids: generalists Drosophila melanogaster and simulans , noni fruit specialist sechellia . The global cellular composition these species’ is well-conserved, predicted a few cell types with different frequencies, notably perineurial glia blood–brain barrier, which validate in vivo Gene expression analysis revealed that evolve at rates patterns, glial populations exhibiting greatest divergence between species. Compared to D. brain, gene patterns are more divergent than —despite their similar phylogenetic distance from —indicating specialization reflected structure function its brain. Expression changes include several metabolic signaling genes, suggestive adaptations novel source nutrition. Additional on genes responsive dietary supplement noni, pointing as sites for both physiological genetic adaptation this fruit. Our represent first comparative datasets “whole” provide comprehensive foundation studying evolvability nervous systems well-defined ecological framework.

Language: Английский

Citations

1

Single cell RNA-seq analysis reveals temporally-regulated and quiescence-regulated gene expression in Drosophila larval neuroblasts DOI Creative Commons
Noah Dillon, Ben Cocanougher, Chhavi Sood

et al.

Neural Development, Journal Year: 2022, Volume and Issue: 17(1)

Published: Aug. 24, 2022

The mechanisms that generate neural diversity during development remains largely unknown. Here, we use scRNA-seq methodology to discover new features of the Drosophila larval CNS across several key developmental timepoints. We identify multiple progenitor subtypes - both stem cell-like neuroblasts and intermediate progenitors change gene expression development, report on candidate markers for each class progenitors. a pool quiescent in newly hatched larvae show they are transcriptionally primed respond insulin signaling pathway exit from quiescence, including relevant components adjacent glial cell type. "temporal transcription factors" (TTFs) expressed at different times lineages. Our work identifies many type specific genes candidates functional roles, generates insight into differentiation trajectory neurons.

Language: Английский

Citations

22

Molecular and cellular origins of behavioral sex differences: a tiny little fly tells a lot DOI Creative Commons
Kosei Sato,

Daisuke Yamamoto

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Oct. 16, 2023

Behavioral sex differences primarily derive from the sexually dimorphic organization of neural circuits that direct behavior. In Drosophila melanogaster , sex-determination genes fruitless ( fru ) and doublesex dsx play pivotal roles in producing sexual dimorphism for Here we examine three groups expressing and/or i.e., P1 cluster, aSP-f aSP-g cluster pairs aDN which causal relationships between behavior characteristics are best illustrated. aSP-f, clusters represent examples where or switches cell-autonomously their neurite structures female-type male-type. Processed sensory inputs impinging on these neurons may result outputs encode different valences, culminate execution distinct according to sex. contrast, is male-specific as its female counterpart undergoes -driven cell death, lowers threshold induction behaviors. We propose products genes, terminal selectors neuronal wiring, induce maintain sex-typical chromatin state at postembryonic stages, orchestrating transcription effector shape single neuron govern survival death.

Language: Английский

Citations

11

Looking across the gap: Understanding the evolution of eyes and vision among insects DOI Creative Commons
Maike Kittelmann, Alistair P. McGregor

BioEssays, Journal Year: 2024, Volume and Issue: 46(5)

Published: April 9, 2024

Abstract The compound eyes of insects exhibit stunning variation in size, structure, and function, which has allowed these animals to use their vision adapt a huge range different environments lifestyles, evolve complex behaviors. Much our knowledge eye development been learned from Drosophila , while visual adaptations behaviors are often more striking better understood studies other insects. However, recent insects, including bees, beetles, butterflies, have begun address this gap by revealing the genetic developmental bases differences morphology key new aspects structure function. Furthermore, technical advances facilitated generation high‐resolution connectomic data insect species that enhances understanding information processing, impact changes processes on evolution behavior. Here, we review breakthroughs propose future integrated research function systems within among represents great opportunity understand remarkable diversification vision.

Language: Английский

Citations

4

Morphological and functional convergence of visual projection neurons from diverse neurogenic origins in Drosophila DOI Creative Commons

Rana N. El‐Danaf,

Katarina Kapuralin, Raghuvanshi Rajesh

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 15, 2025

The Drosophila visual system is a powerful model to study the development of neural circuits. Lobula columnar neurons-LCNs are output neurons that encode features relevant natural behavior. There ~20 classes LCNs forming non-overlapping synaptic optic glomeruli in brain. To address their origin, we used single-cell mRNA sequencing define transcriptome LCN subtypes and identified lines expressed throughout development. We show originate from stem cells four distinct brain regions exhibiting different modes neurogenesis, including ventral dorsal tips outer proliferation center, superficial inner center central this convergence similar illustrates complexity generating neuronal diversity, likely reflects evolutionary origin each subtype detects specific feature might influence behaviors species. Here authors developmental origins Columnar Neurons brain, tracing them regions. highlights diversity.

Language: Английский

Citations

0

A dynamic gene regulatory code drives synaptic development of hippocampal granule cells DOI
Blanca Lorente-Echeverría, Danie Daaboul, Jeroen Vandensteen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 29, 2025

ABSTRACT Connecting neurons into functional circuits requires the formation, maturation, and plasticity of synapses. While advances have been made in identifying individual genes regulating synapse development, molecular programs orchestrating their action during circuit integration remain poorly understood. Here, we take a multiomic approach to reconstruct gene regulatory networks (GRNs), comprising transcription factors (TFs), regions, predicted target genes, hippocampal granule cells (GCs). We find dynamic code, with early late postnatal GRNs cell morphogenesis organization plasticity, respectively. Our results predict sequential regulations, early-active TFs delaying activation later putative synaptic targets. Using loss-of-function approach, identify Bcl6 as regulator pre- postsynaptic structural Smad3 modulator inhibitory transmission, GCs. Together, these findings highlight key GC development.

Language: Английский

Citations

0

Toward a probabilistic definition of neural cell types DOI Creative Commons
Mahéva Andriatsilavo, Bassem A. Hassan

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103035 - 103035

Published: May 6, 2025

A classical view of cell type relies on a definite set stable properties that are critical for brain functions. Single-cell technologies led to an extensive multimodal characterization nervous systems and perhaps achieved one Santiago Ramón y Cajal's dreams: unveil comprehensive the composition. While global analyses structures highlight degree mesoscale stereotypy, finer-scale resolution composition shows significant variance in essential neural cellular phenotypes, including morphology, gene expression, electrophysiology, connectivity. This highlights need novel conceptualization definition "cell type." The challenge modern classification is thus integrate various distinct into unifying descriptor.

Language: Английский

Citations

0

Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity DOI Creative Commons
Chundi Xu,

Tyler B. Ramos,

Edward M. Rogers

et al.

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

Citations

9