期刊
DEVELOPMENT
卷 142, 期 24, 页码 4329-4339出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.124750
关键词
Limb-field (fin-field); Limb bud (fin bud); Lateral plate mesoderm; Cell migration; Chemoattractant; Tbx5a; Fgf24; Holt-Oram syndrome; Zebrafish
资金
- National Center for Research Resources
- National Center for Advancing Translational Sciences National Institutes of Health [UL1 RR024999]
- CBC scholarship from the Chicago Biomedical Consortium with Searle Funds at The Chicago Community Trust
- National Science Foundation Graduate Research Fellowship
- National Institutes of Health [HD072598]
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.
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