PUBLICATION
Asymmetric cell convergence-driven fin bud initiation and pre-pattern requires Tbx5a control of a mesenchymal Fgf signal
- Authors
- Mao, Q., Stinnett, H.K., Ho, R.K.
- ID
- ZDB-PUB-151104-8
- Date
- 2015
- Source
- Development (Cambridge, England) 142(24): 4329-39 (Journal)
- Registered Authors
- Ho, Robert K.
- Keywords
- Limb-field (fin-field), Limb bud (fin bud), Lateral plate mesoderm, Cell migration, Chemoattractant, Tbx5a, Fgf24, Holt–Oram syndrome, Zebrafish
- MeSH Terms
-
- Animal Fins/cytology*
- Animal Fins/embryology*
- Animals
- Body Patterning*
- Cell Movement
- Cell Tracking
- Embryo, Nonmammalian/metabolism
- Fibroblast Growth Factors/metabolism*
- Gene Expression Regulation, Developmental
- Mesoderm/metabolism*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Signal Transduction*/genetics
- Single-Cell Analysis
- T-Box Domain Proteins/genetics
- T-Box Domain Proteins/metabolism*
- Time-Lapse Imaging
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 26525676 Full text @ Development
Citation
Mao, Q., Stinnett, H.K., Ho, R.K. (2015) Asymmetric cell convergence-driven fin bud initiation and pre-pattern requires Tbx5a control of a mesenchymal Fgf signal. Development (Cambridge, England). 142(24):4329-39.
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 3D 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 Holt-Oram Syndrome patients. This study provides a quantitative reference model for fin-field cell motility during vertebrate fin bud initiation and suggests that a pre-pattern of AP fate specification is already present in the fin-field before or during migration as perturbations to these early cell movements result in the alteration of specific fates.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping