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The earliest breakage of left-right symmetry occurs as the result of leftward flow generated by asymmetric beating of nodal cilia, which eventually induces asymmetric Nodal\/Lefty\/Pitx2 expression on the left side of the lateral plate mesoderm. PIERCE1 has been identified as a p53 target gene involved in the DNA damage response. In this study, we found that<jats:italic>Pierce1<\/jats:italic>-null mice exhibit severe laterality defects, including<jats:italic>situs inversus totalis<\/jats:italic>and heterotaxy with randomized<jats:italic>situs<\/jats:italic>and left and right isomerisms. The spectrum of laterality defects was closely correlated with randomized expression of<jats:italic>Nodal<\/jats:italic>and its downstream genes,<jats:italic>Lefty1\/2<\/jats:italic>and<jats:italic>Pitx2<\/jats:italic>. The phenotype of<jats:italic>Pierce1<\/jats:italic>-null mice most closely resembled that of mutant mice with impaired ciliogenesis and\/or ciliary motility of the node. We also found the loss of asymmetric expression of Cerl2, the earliest flow-responding gene in the node of<jats:italic>Pierce1<\/jats:italic>-null embryos. The results suggest that<jats:italic>Pierce1<\/jats:italic>-null embryos have defects in generating a symmetry breaking signal including leftward nodal flow. This is the first report implicating a role for PIERCE1 in the symmetry-breaking step of left-right asymmetry specification.<\/jats:p>","DOI":"10.1038\/srep27932","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T09:57:36Z","timestamp":1466071056000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["PIERCE1 is critical for specification of left-right asymmetry in mice"],"prefix":"10.1038","volume":"6","author":[{"given":"Young Hoon","family":"Sung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Jeoung","family":"Baek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Hwan","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Song","family":"Gho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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