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Loss of ciliary transition zone protein TMEM107 leads to heterotaxy in mice

2019; Elsevier BV; Volume: 460; Issue: 2 Linguagem: Inglês

10.1016/j.ydbio.2019.12.014

1095-564X

Natalia A. Shylo, Elli Emmanouil, Dylan A Ramrattan, Scott D. Weatherbee,

Epigenetics and DNA Methylation

Cilia in most vertebrate left-right organizers are involved in the original break in left-right (L-R) symmetry, however, less is known about their roles in subsequent steps of the cascade – relaying the signaling and maintaining the established asymmetry. Here we describe the L-R patterning cascades in two mutants of a ciliary transition zone protein TMEM107, revealing that near-complete loss of cilia in Tmem107 null leads to left pulmonary isomerism due to the failure of the midline barrier. Contrary, partially retained cilia in the node and the midline of a hypomorphic Tmem107 schlei mutant appear sufficient for the formation of the midline barrier and establishment and maintenance of the L-R asymmetry. Despite misregulation of Shh signaling in both mutants, the presence of normal Lefty1 expression and midline barrier formation in Tmem107 schlei mutants, suggests a requirement for cilia, but not necessarily Shh signaling for Lefty1 expression and midline barrier formation. • Loss of transition zone protein TMEM107 in mice leads to left isomerism. • TMEM107 exhibits functional specificity in different cilia types. • Loss of Tmem107 results in disruption in early L-R patterning events at the node. • Loss of midline cilia correlates with loss of Lefty1 and disrupted midline barrier. • Midline Lefty1 expression can be dissociated from SHH signaling.