Role of pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice

Jeong Hoon Joo, Jae Lee Young, Gustavo C. Munguba, Sean Park, Timothy J. Taxter, Mohamed Y. Elsagga, Moira R. Jackson, S. Paul Oh, Stephen P. Sugrue

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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/β-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/β-catenin signaling. Supporting this view, we demonstrate abnormal activities of Tcf/Lef transcription factors, and alterations in β-catenin level in multiple Pnn hypomorphic tissues. Taken together, the data suggest that Pnn plays important roles during mouse development through its involvement in regulation of Tcf/Lef activity.

Original languageEnglish (US)
Pages (from-to)2147-2158
Number of pages12
JournalDevelopmental Dynamics
Volume236
Issue number8
DOIs
StatePublished - Aug 1 2007

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Keywords

  • Dermomyotome
  • Neural crest
  • Pinin
  • Tcf/lef
  • Vertebral patterning
  • Wnt/β-catenin signaling

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Joo, J. H., Young, J. L., Munguba, G. C., Park, S., Taxter, T. J., Elsagga, M. Y., Jackson, M. R., Oh, S. P., & Sugrue, S. P. (2007). Role of pinin in neural crest, dorsal dermis, and axial skeleton development and its involvement in the regulation of Tcf/Lef activity in mice. Developmental Dynamics, 236(8), 2147-2158. https://doi.org/10.1002/dvdy.21243