Online ISSN: 2187-2988 Print ISSN: 0911-1794
特定非営利活動法人日本小児循環器学会 Japanese Society of Pediatric Cardiology and Cardiac Surgery
Pediatric Cardiology and Cardiac Surgery 33(5): 349-361 (2017)


臓器錯位症候群の発生機序Molecular Mechanism Underlying Heterotaxy and Cardiac Isomerism

1大阪大学大学院医学系研究科心臓再生医療学共同研究講座Cardiac Regeneration and Therapeutics, Graduate School of Medicine, Osaka University ◇ Osaka, Japan

2大阪大学大学院医学系研究科先進幹細胞治療学共同研究講座Advanced Stem Cell Therapy, Graduate School of Medicine, Osaka University ◇ Osaka, Japan

3大阪大学大学院医学系研究科心臓血管外科学Cardiovascular Surgery, Graduate School of Medicine, Osaka University ◇ Osaka, Japan

発行日:2017年9月1日Published: September 1, 2017


In the past two decades, adopting molecular biological approaches helped to deepen our knowledge of molecular mechanisms underlying heterotaxy. However, many critical questions remain unanswered. Previous studies revealed that there are four key steps to establish left–right asymmetry in our bodies. First, the unidirectional leftward flow of extra-embryonic fluid in the node cavity, “Nodal Flow”, breaks the symmetry. Monocilia that localizes at the apical site of the node epithelial cells generate this Nodal Flow, which is translated into the asymmetric expression of the TGFβ superfamily, Nodal, at the node. Second, this asymmetric information of the node is transferred laterally to lateral plate mesoderm. Third, this transferred information induces a robust left-side specific expression of Nodal, followed by the unilateral activation of bicoid-type homeodomain transcription factor, Pitx2, in the left lateral plate mesoderm. Finally, Pitx2 governs left-side specific morphogenesis. Any of the anomalous events in this sequential cascade is, theoretically, a potent cause of heterotaxy and cardiac isomerism. Unfortunately, our knowledge in clinical genetics is still incomplete to integrate the knowledge that originates from model animals. The focus of this review is on an overview of the vital steps involved in generation of left–right asymmetry in mice, with potential application in human pediatric cardiology.

Key words: heterotaxy; monocilia; nodal flow; nodal; pitx2

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