|ZFIN ID: ZDB-PUB-151104-8|
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Asymmetric cell convergence-driven fin bud initiation and pre-pattern requires Tbx5a control of a mesenchymal Fgf signal
Mao, Q., Stinnett, H.K., Ho, R.K.
|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|
|PubMed:||26525676 Full text @ Development|
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.
ABSTRACTTbx5 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.