title: Asymmetric cell convergence-driven zebrafish fin bud initiation and pre-pattern requires Tbx5a control of a mesenchymal Fgf signal.
abstract: Tbx5 plays a pivotal role in vertebrate forelimb initiation, and loss-of-function experiments result in deformed or absent forelimbs in all taxa studied to date. Combining single-cell fate mapping and three-dimensional cell tracking in the zebrafish, we describe a Tbx5a-dependent cell convergence pattern that is both asymmetric and topological within the fin-field lateral plate mesoderm during early fin bud initiation. We further demonstrate that a mesodermal Fgf24 convergence cue controlled by Tbx5a underlies this asymmetric convergent motility. Partial reduction in Tbx5a or Fgf24 levels disrupts the normal fin-field cell motility gradient and results in anteriorly biased perturbations of fin-field cell convergence and truncations in the pectoral fin skeleton, resembling aspects of the forelimb skeletal defects that define individuals with Holt-Oram syndrome. This study provides a quantitative reference model for fin-field cell motility during vertebrate fin bud initiation and suggests that a pre-pattern of anteroposterior fate specification is already present in the fin-field before or during migration because perturbations to these early cell movements result in the alteration of specific fates.
authors.affiliation: Committee on Development, Regeneration and Stem Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Mao
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Haley K
authors.initials: HK
authors.lastname: Stinnett
authors.affiliation: Department of Organismal Biology and Anatomy, University of Chicago, Chicago, IL 60637, USA rkh@uchicago.edu.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Ho
mesh_terms: D058500:Animal Fins / Q000166:cytology* / Q000196:embryology*; D000818:Animals; D019521:Body Patterning; D002465:Cell Movement; D058948:Cell Tracking; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D059010:Single-Cell Analysis; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D059008:Time-Lapse Imaging; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D029961:Zebrafish Proteins; C517774:fgf8a protein, zebrafish; C479567:fibroblast growth factor 24, zebrafish; D005346:Fibroblast Growth Factors
keywords: Cell migration; Chemoattractant; Fgf24; Holt–Oram syndrome; Lateral plate mesoderm; Limb bud (fin bud); Limb-field (fin-field); Tbx5a; Zebrafish