Journal
DEVELOPMENTAL BIOLOGY
Volume 460, Issue 2, Pages 187-199Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2019.12.014
Keywords
Left-right asymmetry; TMEM107; Cilia; Midline barrier; Shh
Categories
Funding
- National Institute of Child Health and Human Development [R01HD093608]
- National Institute of Diabetes and Digestive and Kidney Diseases [P30DK090744]
- National Institute of General Medical Sciences [T32GM007499]
- National Science Foundation Gradate Research Fellowship [DGE-1122492]
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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.
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