A Critical Developmental Interval of Coupling Axon Branching to Synaptic Degradation During Neural Circuit Formation

Dutta, Suchetana; Linneweber, Gerit Arne; Andriatsilavo, Maheva; Hiesinger, P. Robin; Hassan, Bassem

doi:10.2139/ssrn.4076344

Cited by 2 publications

(2 citation statements)

References 41 publications

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“…Using live imaging, we found that the number of fibres containing stable Tubulin gradually increases through development ( Figure 4D-E) until ∼36hAPF when it stabilizes, while the total number of fibres decreases due to resorption back to the lobula ( Figure S2D ). The number of these stable Tub GFP+ fibres at ∼36hAPF precisely predicts the number of adult medulla targeting axons in each individual ( Figure 4F-H, S2E ), well before medulla innervation and synaptogenesis (50hAPF) 3,4 . We tested the idea that dynamic microtubule stabilization prior to ∼36APF is necessary for medulla targeting by treating ex-vivo cultured brains with Nocodazole between 30hAPF and 36hAPF (Figure 4I-M) .…”

Section: Axon Targeting Decision Occurs Prior Distal Target Innervationmentioning

confidence: 67%

“…We observed a similar axonal amplification-stabilization process in the developing chick spinal cord, suggesting a conserved mechanism. Finally, early microtubule patterns predict the adult brain-wiring of an individual in a target-independent manner prior to synapse formation 3,4 . Thus, we show that a temporal succession of genetically encoded stochastic processes explains the emergence of individual wiring variation.…”

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confidence: 99%

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Probabilistic axon targeting dynamics lead to individualized brain wiring

Andriatsilavo

Dumoulin

Dutta

et al. 2022

Preprint

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Developmental variation in brain-wiring contributes to behavioural individuality1,2. However, how and when individualized wiring diagrams emerge and become stable during development remains largely unknown. Here, we explored axon targeting dynamics in individual brains using live-imaging of a developing Drosophila visual circuit and discovered that targeting choice is an algorithmic multi-step growth process with variable outcomes. Using optogenetics, we found that temporally restricted Notch lateral-inhibition defines a subset of neurons with a probabilistic potential to innervate distal targets. Next, axons from NotchOFF neurons amplify into long actin-rich multi-fibre structures necessary for distal growth. A subset of these NotchOFF neurons create distal targeting axons by stabilizing microtubule growth in one of their actin fibres. Amplified axons without tubulin-stabilized fibres retract, resulting in the stochastic selection of a different number of distal targeting axons in each brain. Pharmacological microtubule destabilization suffices to inhibit this targeting. We observed a similar axonal amplification-stabilization process in the developing chick spinal cord, suggesting a conserved mechanism. Finally, early microtubule patterns predict the adult brain- wiring of an individual in a target-independent manner prior to synapse formation3,4. Thus, we show that a temporal succession of genetically encoded stochastic processes explains the emergence of individual wiring variation.

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Section: Axon Targeting Decision Occurs Prior Distal Target Innervationmentioning

confidence: 67%

mentioning

confidence: 99%

Probabilistic axon targeting dynamics lead to individualized brain wiring

Andriatsilavo

Dumoulin

Dutta

et al. 2022

Preprint

Self Cite

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Developmental transcriptional control of mitochondrial homeostasis is required for activity-dependent synaptic connectivity

Mohylyak,

Bengochea,

Pascual-Caro

et al. 2023

Preprint

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During neuronal circuit formation, local control of axonal organelles ensures proper synaptic connectivity. Whether this process is genetically encoded is unclear and if so, its developmental regulatory mechanisms remain to be identified. We hypothesized that developmental transcription factors regulate critical parameters of organelle homeostasis that contribute to circuit wiring. We combined cell type-specific transcriptomics with a genetic screen to discover such factors. We identified Telomeric Zinc finger-Associated Protein (TZAP) as a temporal developmental regulator of neuronal mitochondrial homeostasis genes, including Pink1. In Drosophila, loss of dTzap function during visual circuit development leads to loss of activity-dependent synaptic connectivity, that can be rescued by Pink1 expression. At the cellular level, loss of dTzap/TZAP leads to defects in mitochondrial morphology, attenuated calcium uptake and reduced synaptic vesicle release in fly and mammalian neurons. Our findings highlight developmental transcriptional regulation of mitochondrial homeostasis as a key factor in activity-dependent synaptic connectivity.

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A Critical Developmental Interval of Coupling Axon Branching to Synaptic Degradation During Neural Circuit Formation

Cited by 2 publications

References 41 publications

Probabilistic axon targeting dynamics lead to individualized brain wiring

Probabilistic axon targeting dynamics lead to individualized brain wiring

Developmental transcriptional control of mitochondrial homeostasis is required for activity-dependent synaptic connectivity

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