PIERCE1 is critical for specification of left-right asymmetry in mice.
The specification of left-right asymmetry of the visceral organs is precisely regulated. 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 Pierce1-null mice exhibit severe laterality defects, including situs inversus totalis and heterotaxy with randomized situs and left and right isomerisms. The spectrum of laterality defects was closely correlated with randomized expression of Nodal and its downstream genes, Lefty1/2 and Pitx2. The phenotype of Pierce1-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 Pierce1-null embryos. The results suggest that Pierce1-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.
Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University, Seoul 03722, Republic of Korea.
Young Hoon
YH
Sung
Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University, Seoul 03722, Republic of Korea.
In-Jeoung
IJ
Baek
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Yong Hwan
YH
Kim
Pohang University of Science and Technology, Pohang 37673, Republic of Korea.
Yong Song
YS
Gho
Department of Physiology and Functional Genomics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
S Paul
SP
Oh
Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea.
Young Jae
YJ
Lee
Department of Biochemistry, College of Life Science and Biotechnology and Yonsei Laboratory Animal Research Center, Yonsei University, Seoul 03722, Republic of Korea.
Han-Woong
HW
Lee
D000818:Animals; D019521:Body Patterning; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008648:Mesoderm; D051379:Mice; D018345:Mice, Knockout
D018797:Cell Cycle Proteins; C527471:RbEST47 protein, mouse