Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis

Autor: Rosenbauer, Jakob, Zhang, Chengting, Mattes, Benjamin, Reinartz, Ines, Wedgwood, Kyle, Schindler, Simone, Sinner, Claude, Scholpp, Steffen, Schug, Alexander
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Embryology
Apoptosis
Midbrain
Cell Signaling
Cell Movement
Medicine and Health Sciences
Cell Cycle and Cell Division
Biology (General)
Zebrafish
WNT Signaling Cascade
beta Catenin
Neural Plate
Cell Death
Eukaryota
Brain
Gene Expression Regulation
Developmental
Animal Models
Signaling Cascades
Cell Motility
Protein Transport
Experimental Organism Systems
Cell Processes
Osteichthyes
Neural Crest
embryonic structures
Vertebrates
Anatomy
Biologie
Brainstem
Research Article
Signal Transduction
animal structures
QH301-705.5
Embryonic Development
Cell Migration
Research and Analysis Methods
Directed Cell Migration
Model Organisms
Animals
Cell Lineage
Computer Simulation
ddc:610
Body Patterning
Stochastic Processes
Embryos
Organisms
Biology and Life Sciences
Computational Biology
Cell Biology
Molecular Development
Morphogens
Wnt Proteins
Fish
Animal Studies
Software
Developmental Biology
Zdroj: PLoS Computational Biology
PLoS Computational Biology, Vol 16, Iss 6, p e1007417 (2020)
PLoS Computational Biology 16(6), e1007417-(2020). doi:10.1371/journal.pcbi.1007417
ISSN: 1553-7358
1553-734X
Popis: During embryogenesis, morphogens form a concentration gradient in responsive tissue, which is then translated into a spatial cellular pattern. The mechanisms by which morphogens spread through a tissue to establish such a morphogenetic field remain elusive. Here, we investigate by mutually complementary simulations and in vivo experiments how Wnt morphogen transport by cytonemes differs from typically assumed diffusion-based transport for patterning of highly dynamic tissue such as the neural plate in zebrafish. Stochasticity strongly influences fate acquisition at the single cell level and results in fluctuating boundaries between pattern regions. Stable patterning can be achieved by sorting through concentration dependent cell migration and apoptosis, independent of the morphogen transport mechanism. We show that Wnt transport by cytonemes achieves distinct Wnt thresholds for the brain primordia earlier compared with diffusion-based transport. We conclude that a cytoneme-mediated morphogen transport together with directed cell sorting is a potentially favored mechanism to establish morphogen gradients in rapidly expanding developmental systems.
Author summary How entire organisms develop out of single cells is a long-term challenge in the life sciences. Morphogens are crucial signaling molecules organizing cell fates and patterning by their local concentrations. While many morphogens diffuse freely, specialized cell extrusions can facilitate directed cell-to-cell transport for morphogens of the Wnt/β-Catenin family. We performed simulations of quickly growing tissue take this into account, back to back with in-vivo experiments. Our simulations suggest that stochasticity effects lead to non-physiological fluctuating boundaries of tissue regions if not properly controlled. Such control can be achieved via directed cell sorting and apoptosis. We provide experimental evidence for both mechanisms. We observe a distinct temporal difference between the transport mechanisms, with cytonemes facilitating an earlier establishment of a stable pre-pattern. Overall, simulations suggest that cytoneme-mediated Wnt transport is advantageous over diffusion-based transport and a potential general mechanism to establish morphogen gradients in rapidly expanding developmental systems.
Databáze: OpenAIRE
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