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Here are some papers where **light/optogenetics steers axon (and some dendrite) growth** either by locally photoactivating intracellular guidance machinery or by making guidance receptors light-switchable.
See [[optogenetics]] and [[biosight]] for more information. Related to synthetic biology for programmable tissue morphology.
**Axon guidance by subcellular Rac1 photoactivation (in vivo)**
* **Harris et al., 2020, Dev Cell** — Express **PA-Rac1** in zebrafish motor neurons; tight blue-light ROIs at the growth cone **turn axons on command**, even across normally repulsive somite boundaries; rerouted axons form **functional synapses** and **rescue guidance defects**. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7375170/)
* **Harris et al., 2021 (protocol)** — Step-by-step **optogenetic axon guidance** in embryonic zebrafish using PA-Rac1; details on illumination patterns, timing, and expected turning. [ScienceDirect](https://www.sciencedirect.com/science/article/pii/S2666166721006535?utm_source=chatgpt.com)
**Light-switchable guidance receptors**
* **Endo et al., 2016, Sci Reports** — Engineered **photoactivatable DCC (netrin receptor)** via CRY2 clustering; pulsed blue light **attracts growth cones** (chick DRG) and **navigates axons in vivo** (C. elegans). [Nature](https://www.nature.com/articles/srep23976)
* **Tymanskyj et al., 2025, Mol Biol Cell** — Local optogenetic activation of receptor signaling **remodels growth cones** and redirects outgrowth; a general receptor-level handle for optical guidance. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11809317/?utm_source=chatgpt.com)
**Optogenetic trophic signaling to bias neurite fate/trajectory**
* **Woo et al., 2019, Cell Chemical Biology** — **Opto-TrkB**: local TrkB activation at a neurite tip generates **actin waves**, creates a growth-cone–like domain, and **converts that neurite into the axon**, steering elongation. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3319373/?utm_source=chatgpt.com)
* **Wang et al., 2020, eLife** — **optoRaf**/**optoAKT** pulses promote axon **regeneration** and allow **temporal tuning of regrowth direction** after injury. [eLife](https://elifesciences.org/articles/57395?utm_source=chatgpt.com)
**Foundational & how-to**
* **Wu et al., 2009, Nature** — Original **PA-Rac1** design (LOV-Rac1); reversible, subcellular activation that drives directed protrusion—basis for later neuronal guidance work. [PubMed](https://pubmed.ncbi.nlm.nih.gov/19693014/?utm_source=chatgpt.com)
* **Harris et al., 2021 (review/how-to)** — Overview of **optogenetic axon guidance** concepts and implementation in embryos. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8605397/?utm_source=chatgpt.com)
**Dendrite patterning with optogenetic perturbations**
* **Xu et al., 2024, Dev Cell (review with applications)** — **OptoTrap** of endogenous proteins in neurons reveals **microtubule/kinesin-1 roles in dendrite growth and branch patterning** with precise spatiotemporal control. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11364106/?utm_source=chatgpt.com)
**Review articles**
* **Harris, Wang & Arlotta, 2021 — *STAR Protocols***: a full, worked “optogenetic axon guidance” protocol in zebrafish that doubles as a mini-review (concepts, hardware, illumination strategies, troubleshooting). If you read one piece end-to-end, make it this. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC8605397/?utm_source=chatgpt.com), [PubMed](https://pubmed.ncbi.nlm.nih.gov/34841275/?utm_source=chatgpt.com)
* **Rost et al., 2017 — *Neuron*, “Optogenetic Tools for Subcellular Applications in Neuroscience”**: the definitive survey of subcellular optogenetics (PA-Rac1/LOV, CRY2 clustering, PhyB/PIF, targeting/kinetics), i.e., the exact playbook used for light-guided growth-cone turning. Includes practical design trade-offs and localization strategies. (Open-access PDF.) [Cell](https://www.cell.com/neuron/pdf/S0896-6273%2817%2930916-9.pdf?utm_source=chatgpt.com)
* **Tan et al., 2022 — *Physiological Reviews*, “Optophysiology”**: a broad, modern review of optogenetic actuators/switches with sections on intracellular signaling control and subcellular targeting—useful for choosing/benchmarking tools for axon steering. [Physiological Journals](https://journals.physiology.org/doi/10.1152/physrev.00021.2021?utm_source=chatgpt.com)
* **Johnson & Toettcher, 2018 — *Curr. Opin. Biotechnol.* “Illuminating developmental biology with cellular optogenetics”**: focused on developmental uses of optogenetics; frames how localized photoactivation is applied in vivo (good conceptual context for guidance experiments). [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC6082700/?utm_source=chatgpt.com)
**Two anchor primaries to pair with the reviews**
* **Harris et al., 2020 — *Dev Cell***: landmark demonstration of *in vivo* growth-cone turning and long-range rerouting using PA-Rac1. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC7375170/?utm_source=chatgpt.com)
* **Tymanskyj et al., 2025 — *Mol Biol Cell***: receptor-level optogenetic control of growth-cone dynamics; complements Rac-based guidance with a photoreceptor-proximal strategy. [PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC11809317/?utm_source=chatgpt.com)
# Non-optogenetic axon wiring techniques
Optogenetics is not the only way to determine axon guidance. Protein patterning and 3d printing can provide direct guidance for axon growth. In addition, physical manipulation is another option using AFM probe tips.
[Mechanical manipulation of neurons to control axonal development](https://pmc.ncbi.nlm.nih.gov/articles/PMC4719026/) -- "We show that AFM probe tip with microbeads adhesively contacted onto an axon or dendrite can be pulled to initiate a new neurite that can be mechanically guided to form new synapses at up to 0.8 mm distance in <1 hour. The extension rates achieved are faster than 20 μm/min over millimeter-scale distances and functional connections are established. ur proposed mechanical approach bypasses slow chemical strategies and enables controlled connection to a specific target. We have yet to discover whether there is a fundamental upper limit to these speeds." They should have also tested using an AFM probe tip to dissect, prune or disconnect the neural network.
microfluidics and micro-channels can also constrain the growth direction of certain axons, using geometry and spatial confinement. See 2025-08-28 in the IRC logs..
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