ArticlePLoS biology2010
The role of spatially controlled cell proliferation in limb bud morphogenesis.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 204 citations in OpenAlex.
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- Downstream branches of receptor tyrosine kinase signaling act interdependently to shape the face.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Morphogen gradients are regulated by porous media characteristics of the developing tissue.Development (Cambridge, England) · 2025Article
- Quantifying the relationship between cell proliferation and morphology during development of the face.Development (Cambridge, England) · 2025Article
- Proliferation symmetry breaking in growing tissues.bioRxiv : the preprint server for biology · 2024Article
- A fibronectin gradient remodels mixed-phase mesoderm.Science advances · 2024Article
- Mesenchymal Wnts are required for morphogenetic movements of calvarial osteoblasts during apical expansion.Development (Cambridge, England) · 2024Article
- Compressive stress gradients direct mechanoregulation of anisotropic growth in the zebrafish jaw joint.PLoS computational biology · 2024Article
- The first embryo, the origin of cancer and animal phylogeny. III. The totipotency as revealed by morphogenesis and the neoplasia controlled by cellular differentiation.Journal of biosciences · 2024Review
- An archetype and scaling of developmental tissue dynamics across species.Nature communications · 2023Article
- Spatial consistency of cell growth direction during organ morphogenesis requires CELLULOSE SYNTHASE INTERACTIVE1.Cell reports · 2023Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Although the vertebrate limb bud has been studied for decades as a model system for spatial pattern formation and cell specification, the cellular basis of its distally oriented elongation has been a relatively neglected topic by comparison. The conventional view is that a gradient of isotropic proliferation exists along the limb, with high proliferation rates at the distal tip and lower rates towards the body, and that this gradient is the driving force behind outgrowth. Here we test this hypothesis by combining quantitative empirical data sets with computer modelling to assess the potential role of spatially controlled proliferation rates in the process of directional limb bud outgrowth. In particular, we generate two new empirical data sets for the mouse hind limb--a numerical description of shape change and a quantitative 3D map of cell cycle times--and combine these with a new 3D finite element model of tissue growth. By developing a parameter optimization approach (which explores spatial patterns of tissue growth) our computer simulations reveal that the observed distribution of proliferation rates plays no significant role in controlling the distally extending limb shape, and suggests that directional cell activities are likely to be the driving force behind limb bud outgrowth. This theoretical prediction prompted us to search for evidence of directional cell orientations in the limb bud mesenchyme, and we thus discovered a striking highly branched and extended cell shape composed of dynamically extending and retracting filopodia, a distally oriented bias in Golgi position, and also a bias in the orientation of cell division. We therefore provide both theoretical and empirical evidence that limb bud elongation is achieved by directional cell activities, rather than a PD gradient of proliferation rates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.