title: Mapping the dynamic expression of Wnt11 and the lineage contribution of Wnt11-expressing cells during early mouse development.
abstract: Planar cell polarity (PCP) signaling is an evolutionarily conserved mechanism that coordinates polarized cell behavior to regulate tissue morphogenesis during vertebrate gastrulation, neurulation and organogenesis. In Xenopus and zebrafish, PCP signaling is activated by non-canonical Wnts such as Wnt11, and detailed understanding of Wnt11 expression has provided important clues on when, where and how PCP may be activated to regulate tissue morphogenesis. To explore the role of Wnt11 in mammalian development, we established a Wnt11 expression and lineage map with high spatial and temporal resolution by creating and analyzing a tamoxifen-inducible Wnt11-CreER BAC (bacterial artificial chromosome) transgenic mouse line. Our short- and long-term lineage tracing experiments indicated that Wnt11-CreER could faithfully recapitulate endogenous Wnt11 expression, and revealed for the first time that cells transiently expressing Wnt11 at early gastrulation were fated to become specifically the progenitors of the entire endoderm. During mid-gastrulation, Wnt11-CreER expressing cells also contribute extensively to the endothelium in both embryonic and extraembryonic compartments, and the endocardium in all chambers of the developing heart. In contrast, Wnt11-CreER expression in the myocardium starts from late-gastrulation, and occurs in three transient, sequential waves: first in the precursors of the left ventricular (LV) myocardium from E7.0 to 8.0; subsequently in the right ventricular (RV) myocardium from E8.0 to 9.0; and finally in the superior wall of the outflow tract (OFT) myocardium from E8.5 to 10.5. These results provide formal genetic proof that the majority of the endocardium and myocardium diverge by mid-gastrulation in the mouse, and suggest a tight spatial and temporal control of Wnt11 expression in the myocardial lineage to coordinate with myocardial differentiation in the first and second heart field progenitors to form the LV, RV and OFT. The insights gained from this study will also guide future investigations to decipher the role of non-canonical Wnt/PCP signaling in endoderm development, vasculogenesis and heart formation.
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Sinha
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences & Department of Medicine, University of California, San Diego, United States.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Davis
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences & Department of Medicine, University of California, San Diego, United States.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Evans
authors.affiliation: Department of Genetics, School of Medicine, Case Western Reserve University, United States.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, United States. Electronic address: j18wang@uab.edu.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D019070:Cell Lineage; D022202:Chromosomes, Artificial, Bacterial / Q000378:metabolism; D004622:Embryo, Mammalian / Q000098:blood supply / Q000378:metabolism; D047108:Embryonic Development; D004707:Endoderm / Q000196:embryology / Q000378:metabolism; D054262:Gastrulation; D019426:Integrases / Q000378:metabolism; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism; D054240:Primitive Streak / Q000196:embryology / Q000378:metabolism; D019076:Transgenes; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; C508957:Wnt11 protein, mouse; C045073:Cre recombinase; D019426:Integrases
keywords: Endoderm specification; Endothelial/endocardial specification; Fate mapping; Gastrulation; Heart development; Planar cell polarity; Wnt11