Control of Tissue Development by Morphogens

Kicheva, Anna; Briscoe, James

doi:10.1146/annurev-cellbio-020823-011522

Cited by 52 publications

(23 citation statements)

References 222 publications

(267 reference statements)

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“…By asking how SHH morphogen gradient size can be regulated, we discovered that prior models of morphogen diffusion could not adequately describe formation of SHH gradients [39][40][41] . Whereas prior models assume tissues to be uniform continuous spaces, our model considers tissues to be structured assemblies of discrete cells, separated by diffusion barriers.…”

Section: Discussionmentioning

confidence: 99%

Diffusion barriers imposed by tissue topology shape morphogen gradients

Schlissel,

Meziane,

Narducci

et al. 2024

Preprint

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Animals use a small number of morphogens to pattern tissues, but it is unclear how evolution modulates morphogen signaling range to match tissues of varying sizes. Here, we used single molecule imaging in reconstituted morphogen gradients and in tissue explants to determine that Hedgehog diffused extracellularly as a monomer, and rapidly transitioned between membrane- confined and -unconfined states. Unexpectedly, the vertebrate-specific protein SCUBE1 expanded Hedgehog gradients by accelerating the transition rates between states without affecting the relative abundance of molecules in each state. This observation could not be explained under existing models of morphogen diffusion. Instead, we developed a topology-limited diffusion model in which cell-cell gaps create diffusion barriers, and morphogens can only overcome the barrier by passing through a membrane-unconfined state. Under this model, SCUBE1 promotes Hedgehog secretion and diffusion by allowing it to transiently overcome diffusion barriers. This multiscale understanding of morphogen gradient formation unified prior models and discovered novel knobs that nature can use to tune morphogen gradient sizes across tissues and organisms.

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Section: Discussionmentioning

confidence: 99%

Diffusion barriers imposed by tissue topology shape morphogen gradients

Schlissel,

Meziane,

Narducci

et al. 2024

Preprint

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“…2b), and maintain an extremely conserved fate mapping role. However, without the existence of tightly controlled mechanical neurulation and gastrulation, the morphogens would not induce the proper cells and we would not obtain the patterned neural tube that defines all vertebrate organogenesis [41].…”

Section: Neural Inductionmentioning

confidence: 99%

The Phylotypic Brain of Vertebrates, from Neural Tube Closure to Brain Diversification

Senovilla-Ganzo,

García-Moreno

2024

Brain Behav Evol

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The phylotypic or intermediate stages are thought to be the most evolutionary conserved stages throughout embryonic development. The contrast with divergent early and later stages derived in the concept of the evo-devo hourglass model. Nonetheless, this developmental constraint has been studied as a whole embryo process, not at organ level. In this review, we explore brain development to assess the existence of an equivalent brain developmental hourglass. In the specific case of vertebrates, we propose to split the brain developmental stages into: 1) Early: Neurulation, when the neural tube arises after gastrulation. 2) Intermediate: Brain patterning and segmentation, when the neuromere identities are established. 3) Late: Neurogenesis and maturation, the stages when the neurons acquire their functionality. Moreover, we extend this analysis to chordates and deuterostomes brain development to unravel the evolutionary origin of this evo-devo constraint. Based on the existing literature, we hypothesise that a major conservation of the phylotypic brain might be due to the pleiotropy of the inductive regulatory networks, which are predominantly expressed at this stage. In turn, earlier stages such as neurulation are rather mechanical processes, whose regulatory networks seem to adapt to environment or maternal geometries. The later stages are also controlled by inductive regulatory networks, but their effector genes are mostly tissue specific and functional, allowing diverse developmental programs to generate current brain diversity. Nonetheless, all stages of the hourglass are highly interconnected: divergent neurulation must have a vertebrate shared end-product to reproduce the vertebrate phylotypic brain, and the boundaries and transcription factor code established during the highly conserved patterning will set the bauplan for the specialised and diversified adult brain.

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“…Despite the widespread functioning of gradients in both development and disease, it has remained challenging to monitor natural signaling gradients together with cell and tissue responses over time. In contexts with limited tissue reorganisation, it has been possible to infer how cells react to signal gradients ( 3 ). However, for contexts in which three-dimensional tissue organization remodels substantially over time, there are significant barriers to interpreting the connection between signal inputs and behavioural outputs of cells.…”

Section: Introductionmentioning

confidence: 99%

Pattern formation along signaling gradients driven by active droplet behaviour of cell groups

Ford,

Celora,

Westbrook

et al. 2024

Preprint

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Gradients of extracellular signals organise cells in tissues. Although there are several models for how gradients can pattern cell behaviour, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell-cell and cell-signal interactions are continually changing.Dictyosteliumcells follow gradients of their nutritional source to feed and maintain their undifferentiated state. Using light sheet imaging to simultaneously monitor signaling, single cell and population dynamics, we show that the cells migrate towards nutritional gradients in swarms. As swarms advance, they deposit clumps of cells at the rear, triggering differentiation. Clump deposition is explained by a physical model in which cell swarms behave as active droplets: cells proliferate within the swarm, with clump shedding occurring at a critical population size, at which cells at the rear no longer perceive the gradient and are not retained by the emergent surface tension of the swarm. The droplet model predicts vortex motion of the cells within the swarm emerging from the local transfer of propulsion forces, a prediction validated by 3D tracking of single cells. This active fluid behaviour reveals a developmental mechanism we term “musical chairs” decision-making, in which the decision to proliferate or differentiate is determined by the position of a cell within the group as it bifurcates.

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Control of Tissue Development by Morphogens

Cited by 52 publications

References 222 publications

Diffusion barriers imposed by tissue topology shape morphogen gradients

Diffusion barriers imposed by tissue topology shape morphogen gradients

The Phylotypic Brain of Vertebrates, from Neural Tube Closure to Brain Diversification

Pattern formation along signaling gradients driven by active droplet behaviour of cell groups

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