A global timing mechanism regulates cell-type-specific wiring programmes

Jain, Shuchi; Lin, Ying; Kurmangaliyev, Yerbol Z.; Valdes-Aleman, Javier; LoCascio, Samuel A.; Mirshahidi, Parmis; Parrington, Brianna; Zipursky, S. Lawrence

doi:10.1038/s41586-022-04418-5

Cited by 28 publications

(41 citation statements)

References 75 publications

(86 reference statements)

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“…Modularity. The modularity statistic, Q, quantifies the extent to which the network can be subdivided into clearly delineated groups: 𝑄 = 1 𝑙 J •𝑎 ",$ − 𝑘 " 𝑘 ,$ 𝑙 € 𝛿 C N C O ",$∈_ (13) where 𝑚 " is the module containing node 𝑖, and 𝛿 C N C O = 1 if 𝑚 " = 𝑚 $ , and 0 otherwise.…”

Section: Network Statisticsmentioning

confidence: 99%

Homophilic wiring principles underpin neuronal network topologyin vitro

Akarca

Dunn

Hornauer

et al. 2022

Preprint

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Economical efficiency has been a popular explanation for how networks organize themselves within the developing nervous system. However, the precise nature of the economic negotiations governing this self- organization remain unclear. We approach this problem by combining high-density microelectrode array (HD-MEA) recordings, which allow for detailed characterization of the ongoing extracellular electrical activity of individual neurons in vitro, with a generative modeling approach capable of simulating network formation. The best fitting model uses a homophilic generative wiring principle in which neurons form connections to other neurons with similar connectivity patterns to themselves. This homophily-based mechanism for neuronal network emergence accounts for a wide range of observations that are described, but not sufficiently explained, by traditional analyses of network topology. Using rodent and human monolayer and organoid cultures, we show that homophilic generative mechanisms account for the topology of emerging cellular functional connectivity, representing an important wiring principle and determining factor of neuronal network formation in vitro.

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Section: Network Statisticsmentioning

confidence: 99%

Homophilic wiring principles underpin neuronal network topologyin vitro

Akarca

Dunn

Hornauer

et al. 2022

Preprint

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“…S5F ). Interestingly, upon Hr3 knock-down, this downregulation is delayed but not abolished in all 5 lamina neurons 14 . We thus asked whether Blimp-1 functions as a repressor of Mef2 , through which Hr3 might act.…”

Section: Resultsmentioning

confidence: 94%

“… A-B, FRT40A (control) and SoxN NC 14 MARCM clones labeled with TmX/Tm4,6-Gal4 and CD4tdGFP in adult brains. A, Quantification of B, based on Aop-only (Tm4) and Aop+SoxN (Tm6) neurons.…”

Section: Resultsmentioning

confidence: 99%

“…UMAP visualization was calculated using 3 principal components (PCs). E-G, scRNA- seq datasets of ( E ) L1-5 neurons at P48 expressing Hr3 RNAi 14 , ( F ) simulated-single Erm mutant L3 neurons from (D), ( G ) Tm1/2/4/6 neurons at P50 overexpressing UAS-pdm3.short (Fig. 1).…”

Section: Figure S1mentioning

confidence: 99%

“…Specific genetic programs must exist to coordinate these since most spatial and tTFs are not maintained in neurons 10 . These genetic programs also need to interact with extrinsic signals 14 to ensure that correct downstream “effector” genes are activated at the correct times.…”

Section: Introductionmentioning

confidence: 99%

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Coordinated control of neuronal differentiation and wiring by a sustained code of transcription factors

Özel

Gibbs

Holguera

et al. 2022

Preprint

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The enormous diversity of cell types in nervous systems presents a challenge in identifying the genetic mechanisms that encode it. Here, we report that nearly 200 distinct neurons in the Drosophila visual system can each be defined by unique combinations of ∼10 transcription factors that are continuously expressed by them. We show that targeted modifications of this ‘selector’ code induce predictable conversions of cell fates between neurons in vivo. These conversions appear morphologically and transcriptionally complete, arguing for a conserved gene regulatory program that jointly instructs both the type-specific development and the terminal features of neurons. Cis-regulatory sequence analysis of open chromatin links one of these selectors to an upstream patterning gene in stem cells that specifies neuronal fates. Experimentally validated network models show that selectors interact with ecdysone signaling to regulate downstream effectors controlling brain wiring. Our results provide a generalizable framework of how specific fates are initiated and maintained in postmitotic neurons.

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