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data-landing_url="https://www.academia.edu/100112642/Dynamical_mechanisms_for_skeletal_pattern_formation_in_the_vertebrate_limb" data-login_uri="https://www.academia.edu/registrations/google_one_tap" data-moment_callback="onGoogleOneTapEvent" id="g_id_onload"></div><div class="ds-top-related-works--grid-container"><div class="ds-related-content--container ds-top-related-works--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="0" data-entity-id="14593551" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14593551/Multiscale_Models_for_Vertebrate_Limb_Development">Multiscale Models for Vertebrate Limb Development</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33732628" href="https://independent.academia.edu/MarkAlber">Mark Alber</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33728423" href="https://pan-pl.academia.edu/BogdanKazmierczak">Bogdan Kazmierczak</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33545496" href="https://nd.academia.edu/YongTaoZhang">Yong-Tao Zhang</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Current Topics in Developmental Biology, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Multiscale Models for Vertebrate Limb Development","attachmentId":44049642,"attachmentType":"pdf","work_url":"https://www.academia.edu/14593551/Multiscale_Models_for_Vertebrate_Limb_Development","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" 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class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="114709740" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/114709740/Divide_accumulate_differentiate_cell_condensation_in_skeletal_development_revisited">Divide, accumulate, differentiate: cell condensation in skeletal development revisited</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="107896630" href="https://independent.academia.edu/TsutomuMiyake">Tsutomu Miyake</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The International journal of developmental biology, 1995</p><p class="ds-related-work--abstract ds2-5-body-sm">Cell condensation is a pivotal stage in skeletal development. 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Therefore, during osteogenesis, condensation amplifies th...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Divide, accumulate, differentiate: cell condensation in skeletal development revisited","attachmentId":111333060,"attachmentType":"pdf","work_url":"https://www.academia.edu/114709740/Divide_accumulate_differentiate_cell_condensation_in_skeletal_development_revisited","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/114709740/Divide_accumulate_differentiate_cell_condensation_in_skeletal_development_revisited"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="56659059" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/56659059/Growth_Based_Morphogenesis_of_Vertebrate_Limb_Bud">Growth Based Morphogenesis of Vertebrate Limb Bud</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="39574969" href="https://kyushu-u.academia.edu/YohIwasa">Yoh Iwasa</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Bulletin of Mathematical Biology, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Growth Based Morphogenesis of Vertebrate Limb Bud","attachmentId":71936306,"attachmentType":"pdf","work_url":"https://www.academia.edu/56659059/Growth_Based_Morphogenesis_of_Vertebrate_Limb_Bud","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/56659059/Growth_Based_Morphogenesis_of_Vertebrate_Limb_Bud"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="3986169" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/3986169/Activator_inhibitor_dynamics_of_vertebrate_limb_pattern_formation">Activator-inhibitor dynamics of vertebrate limb pattern formation</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="4790456" href="https://independent.academia.edu/RamrayBhat">Ramray Bhat</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Birth Defects Research Part C-embryo Today-reviews, 2007</p><p class="ds-related-work--abstract ds2-5-body-sm">The development of the vertebrate limb depends on an interplay of cellular differentiation, pattern formation, and tissue morphogenesis on multiple spatial and temporal scales. While numerous gene products have been described that participate in, and influence, the generation of the limb skeletal pattern, an understanding of the most salient feature of the developing limb—its quasiperiodic arrangement of bones, requires additional organizational principles. We review several such principles, drawing on concepts of physics and chemical dynamics along with molecular genetics and cell biology. First, a “core mechanism” for precartilage mesenchymal condensation is described, based on positive autoregulation of the morphogen transforming growth factor (TGF)-β, induction of the extracellular matrix (ECM) protein fibronectin, and focal accumulation of cells via haptotaxis. This core mechanism is shown to be part of a local autoactivation-lateral inhibition (LALI) system that ensures that the condensations will be regularly spaced. Next, a “bare-bones” model for limb development is described in which the LALI-core mechanism is placed in a growing geometric framework with predifferentiated “apical,” differentiating “active,” and irreversibly differentiated “frozen” zones defined by distance from an apical source of a fibroblast growth factor (FGF)-type morphogen. This model is shown to account for classic features of the developing limb, including the proximodistal (PD) emergence over time of increasing numbers of bones. We review earlier and recent work suggesting that the inhibitory component of the LALI system for condensation may not be a diffusible morphogen, and propose an alternative mechanism for lateral inhibition, based on synchronization of oscillations of a Hes mediator of the Notch signaling pathway. Finally, we discuss how viewing development as an interplay between molecular-genetic and dynamic physical processes can provide new insight into the origin of congenital anomalies. Birth Defects Research (Part C) 81:305–319, 2007. © 2008 Wiley-Liss, Inc.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Activator-inhibitor dynamics of vertebrate limb pattern formation","attachmentId":50098235,"attachmentType":"pdf","work_url":"https://www.academia.edu/3986169/Activator_inhibitor_dynamics_of_vertebrate_limb_pattern_formation","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/3986169/Activator_inhibitor_dynamics_of_vertebrate_limb_pattern_formation"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="34144922" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/34144922/The_mesenchymal_factor_FGF10_initiates_and_maintains_the_outgrowth_of_the_chick_limb_bud_through_interaction_with_FGF8_an_apical_ectodermal_factor">The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="67020128" href="https://independent.academia.edu/SumihareNoji">Sumihare Noji</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Development, 1997</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"The mesenchymal factor, FGF10, initiates and maintains the outgrowth of the chick limb bud through interaction with FGF8, an apical ectodermal factor","attachmentId":54069389,"attachmentType":"pdf","work_url":"https://www.academia.edu/34144922/The_mesenchymal_factor_FGF10_initiates_and_maintains_the_outgrowth_of_the_chick_limb_bud_through_interaction_with_FGF8_an_apical_ectodermal_factor","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/34144922/The_mesenchymal_factor_FGF10_initiates_and_maintains_the_outgrowth_of_the_chick_limb_bud_through_interaction_with_FGF8_an_apical_ectodermal_factor"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="18231281" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/18231281/Morphogenesis_of_precursor_subpopulations_of_chicken_limb_mesenchyme_in_three_dimensional_collagen_gel_culture">Morphogenesis of precursor subpopulations of chicken limb mesenchyme in three dimensional collagen gel culture</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38217099" href="https://independent.academia.edu/RogerMarkwald">Roger Markwald</a></div><p class="ds-related-work--metadata ds2-5-body-xs">The Anatomical Record, 1990</p><p class="ds-related-work--abstract ds2-5-body-sm">Although homogeneous in appearance, several lines of evidence suggest early (stage 17-19) limb mesenchymal cells are committed to particular cell lineages, e.g., myogenic or chondrogenic. However, subsequent expression of cell or tissue phenotype in the developing limb does not occur in a randomized process but rather in a spatially specific pattern. The potential regulatory mechanisms controlling the &amp;quot;patterned&amp;quot; expression of tissue phenotype in the limb have not been resolved. The purpose of this study was to determine if, prior to the formation of an apical ectodermal ridge, nondissociated limb mesenchyme has inherent morphogenetic potential to form nonrandomized patterns of tissue organization. The hypotheses to be tested were that, if provided a spatially permissive culture environment, 1) mesenchymal cells committed to a particular lineage would segregate into precursor (sub)populations prior to overt expression of phenotype and 2) the ultimate expression of a tissue phenotype may be regulated, in part, by histogenic interactions between the precursor cell groups. For these studies, mesoblasts (intact mesenchyme minus ectoderm) from stage 17-19 hindlimb buds were explanted intact to the surface of a 1-3 mm thick hydrated lattice of repolymerized type I collagen and incubated for 2-11 days. Examination of cultures at variable intervals revealed three distinct temporal sequences (periods) which were arbitrarily termed early morphogenesis (0-3 days), cytodifferentiation (3-5.5 days), and primitive tissue formation (5.5-11 days) based on similarities to in situ limb development. By the end of the first period, the mesenchymal cells had sorted into three distinct precursor populations: 1) an epithelial-like outgrowth of premyogenic and prefibrogenic cells at the surface of the gel lattice (termed the &amp;quot;surface subset&amp;quot;) which circumscribed, 2) a centrally positioned prechondrogenic condensate (&amp;quot;central subset&amp;quot;), and overlaid 3) a dispersed, population of free cells that invaded the collagen lattice (&amp;quot;seeded subset&amp;quot;). Subsequent cytodifferentiation led to the appearance of multinucleated myotubes within the surface subset and chondrification of the central subset. Cells of the seeded subset remained dispersed within the collagen lattice. Primitive histogenic events were initiated during the final period of development including 1) at sites where surface cells established boundaries with the central subset, collectives or &amp;quot;bundles&amp;quot; of variable sized myotubes were formed which became partially ensheathed by the attenuated processes of fibroblastlike cells; and 2) a secondary site of chondrogenic activity was initiated within the gel lattice at the boundary between the central and seeded cell populations. 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Hornbruch</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Current Biology, 1995</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"A role for FGF-8 in the initiation and maintenance of vertebrate limb bud outgrowth","attachmentId":51249101,"attachmentType":"pdf","work_url":"https://www.academia.edu/30815928/A_role_for_FGF_8_in_the_initiation_and_maintenance_of_vertebrate_limb_bud_outgrowth","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/30815928/A_role_for_FGF_8_in_the_initiation_and_maintenance_of_vertebrate_limb_bud_outgrowth"><span 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limb development plays an indispensable role in subsequent autopod morphogenesis</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="35744620" href="https://independent.academia.edu/CuilingLi">Cuiling Li</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Development, 2005</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis","attachmentId":85540783,"attachmentType":"pdf","work_url":"https://www.academia.edu/78522294/FGFR1_function_at_the_earliest_stages_of_mouse_limb_development_plays_an_indispensable_role_in_subsequent_autopod_morphogenesis","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 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