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

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.