Centrosome‐mediated microtubule remodeling during axon formation in human iPSC‐derived neurons

Lindhout, Feline W; Portegies, Sybren; Kooistra, Robbelien; Herstel, Lotte J; Stucchi, Riccardo; Hummel, Jessica J.A.; Scheefhals, Nicky; Katrukha, Eugene A.; Altelaar, Maarten; MacGillavry, Harold D.; Wierenga, Corette J.; Hoogenraad, Casper C.

doi:10.15252/embj.2020106798

Cited by 8 publications

(8 citation statements)

References 53 publications

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“…In agreement, generation of cultured neurons with multiple centrosomes by preventing cytokinesis results in the formation of multiple neurites originating close to the centrosomes ( De Anda et al, 2005 ). Work in dissociated neurons, cortical slices and stem cell-derived neurons also supports centrosome activity in early neurite outgrowth and axon specification ( De Anda et al, 2005 , 2010 ; Steiss, 2010 ; Lindhout et al, 2021 ). Centriole depletion in stage 2 stem-cell derived neurons results in decreased growth cone size of the immature neurites, an effect mimicked by nocodazole treatment, suggesting a microtubule-mediated mechanism ( Lindhout et al, 2021 ).…”

Section: Regulation Of Microtubules In Neurite Initiationmentioning

confidence: 80%

“…Neuro2A) or PC-12 cells, which form non-specific neurites, but these cells are likely to substantially differ from neurons ( Sainath and Gallo, 2015 ). This issue has recently been circumvented through the use of human pluripotent stem cell-derived neurons, which facilitate monitoring of de-novo neurite initiation during human neuronal differentiation ( Lindhout et al, 2021 ).…”

Section: Studying Neuronal Polarity and Morphogenesismentioning

confidence: 99%

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Establishing neuronal polarity: microtubule regulation during neurite initiation

Higgs

Das

2022

Oxford Open Neuroscience

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The initiation of nascent projections, or neurites from the neuronal cell body is the first stage in the formation of axons and dendrites, and thus a critical step in establishment of neuronal architecture and nervous system development. Neurite formation relies on the polarised remodelling of microtubules, which dynamically direct and reinforce cell shape and provide tracks for cargo transport and force generation. Within neurons, microtubule behaviour and structure are tightly controlled by an array of regulatory factors. Although microtubule regulation in the later stages of axon development is relatively well understood, how microtubules are regulated during neurite initiation is rarely examined. Here, we discuss how factors that direct microtubule growth, remodelling, stability, and positioning influence neurite formation. In addition, we consider microtubule organisation by the centrosome, and modulation by the actin and intermediate filament networks to provide an up-to-date picture of this vital stage in neuronal development.

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Section: Regulation Of Microtubules In Neurite Initiationmentioning

confidence: 80%

Section: Studying Neuronal Polarity and Morphogenesismentioning

confidence: 99%

Establishing neuronal polarity: microtubule regulation during neurite initiation

Higgs

Das

2022

Oxford Open Neuroscience

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“…Two recent reports examine how hiPSC neurons polarize with similarities and differences compared to murine neurons in vitro ( Lindhout et al, 2020 , 2021 ). For example, the timing of polarity acquisition is significantly slower.…”

Section: The Shadows Of Neuronal Polaritymentioning

confidence: 99%

Perspectives on Mechanisms Supporting Neuronal Polarity From Small Animals to Humans

Wilson¹,

Moyano²,

Cáceres³

2022

Front. Cell Dev. Biol.

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Axon-dendrite formation is a crucial milestone in the life history of neurons. During this process, historically referred as “the establishment of polarity,” newborn neurons undergo biochemical, morphological and functional transformations to generate the axonal and dendritic domains, which are the basis of neuronal wiring and connectivity. Since the implementation of primary cultures of rat hippocampal neurons by Gary Banker and Max Cowan in 1977, the community of neurobiologists has made significant achievements in decoding signals that trigger axo-dendritic specification. External and internal cues able to switch on/off signaling pathways controlling gene expression, protein stability, the assembly of the polarity complex (i.e., PAR3-PAR6-aPKC), cytoskeleton remodeling and vesicle trafficking contribute to shape the morphology of neurons. Currently, the culture of hippocampal neurons coexists with alternative model systems to study neuronal polarization in several species, from single-cell to whole-organisms. For instance, in vivo approaches using C. elegans and D. melanogaster, as well as in situ imaging in rodents, have refined our knowledge by incorporating new variables in the polarity equation, such as the influence of the tissue, glia-neuron interactions and three-dimensional development. Nowadays, we have the unique opportunity of studying neurons differentiated from human induced pluripotent stem cells (hiPSCs), and test hypotheses previously originated in small animals and propose new ones perhaps specific for humans. Thus, this article will attempt to review critical mechanisms controlling polarization compiled over decades, highlighting points to be considered in new experimental systems, such as hiPSC neurons and human brain organoids.

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“…Early studies showed that the centrosome and Golgi polarize towards the selected axon prior to its extension [ 64 ]. Additionally, centrosome-derived microtubules are essential for the elongation process [ 65 , 66 ]. Although it cannot be ruled out that the centrosome is merely responding to polarity cues, some have suggested that the positioning of the centrosome selects the axon.…”

Section: Functions Of the Interphase Centrosomementioning

confidence: 99%

Centrosome instability: when good centrosomes go bad

Ryniawec

Rogers

2021

Cell. Mol. Life Sci.

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The centrosome is a tiny cytoplasmic organelle that organizes and constructs massive molecular machines to coordinate diverse cellular processes. Due to its many roles during both interphase and mitosis, maintaining centrosome homeostasis is essential to normal health and development. Centrosome instability, divergence from normal centrosome number and structure, is a common pathognomonic cellular state tightly associated with cancers and other genetic diseases. As novel connections are investigated linking the centrosome to disease, it is critical to understand the breadth of centrosome functions to inspire discovery. In this review, we provide an introduction to normal centrosome function and highlight recent discoveries that link centrosome instability to specific disease states.

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Centrosome‐mediated microtubule remodeling during axon formation in human iPSC‐derived neurons

Cited by 8 publications

References 53 publications

Establishing neuronal polarity: microtubule regulation during neurite initiation

Establishing neuronal polarity: microtubule regulation during neurite initiation

Perspectives on Mechanisms Supporting Neuronal Polarity From Small Animals to Humans

Centrosome instability: when good centrosomes go bad

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