Journal
DEVELOPMENTAL DYNAMICS
Volume 236, Issue 8, Pages 2147-2158Publisher
WILEY
DOI: 10.1002/dvdy.21243
Keywords
pinin; Wnt/beta-catenin signaling; Tcf/lef; neural crest; dermomyotome; vertebral patterning
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Funding
- NEI NIH HHS [EY007883] Funding Source: Medline
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Previous in vitro studies have indicated multiple and varied roles of Pinin (PNN); however, its in vivo role has remained unclear. Here, we report generation of null, hypomorphic, and conditional Pnn alleles in mice. We found that insertion of neomycin-resistance cassette into intron 8 of Pnn resulted in knockdown of Pnn, which allowed Pnn hypomorphic embryos to pass peri-implantation lethality. These mice are lethal at perinatal stages and exhibit defects in the cardiac outflow tract, palate, dorsal dermis, and axial skeleton. Since Wnt/beta-catenin signaling has been shown to play pivotal roles in development of all tissues affected by Pnn hypomorphism, we speculated that Pnn may affect Wnt/beta-catenin signaling. Supporting this view, we demonstrate abnormal activities of Tcf/Lef transcription factors, and alterations in P-catenin level in multiple Pnn hypomorphic tissues. Taken together, the data suggest that Pun plays important roles during mouse development through its involvement in regulation of Tcf/Lef activity.
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