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Presence of midline cilia supersedes the expression of Lefty1 in forming the midline barrier during the establishment of left-right asymmetry

View ORCID ProfileNatalia A Shylo, Dylan Ramrattan, View ORCID ProfileScott D Weatherbee
doi: https://doi.org/10.1101/324533
Natalia A Shylo
Yale University, Genetics Department
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Dylan Ramrattan
Yale University, Genetics Department
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Scott D Weatherbee
Yale University, Genetics Department
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ABSTRACT

Cilia in the vertebrate left-right organizer are required for the original break in left-right (L-R) symmetry. Subsequently, proper L-R patterning relies on asymmetric expression of Nodal in the lateral plate mesoderm (LPM). Lefty1, expressed in the embryonic midline, has been defined as the midline barrier, restricting the expression of Nodal to the left LPM. Here we use the mouse ciliary transition zone mutant Mks1krc that has left isomerism and bilateral expression of the NODAL target Pitx2, to reveal that the expression of Lefty1 in the midline is insufficient for the establishment of the midline barrier. We further show through a comparison of two Tmem107 mutants that cilia in the midline are required to supplement Lefty1 expression and establish the functional midline barrier. Tmem107null mutants have no cilia in the midline and display left isomerism due to the loss of the midline barrier, whereas Tmem107schlei hypomorphic mutants have numerous cilia in the node and the midline, leading to normal Lefty1 expression and L-R patterning. This study reveals a novel role for cilia in the maintenance of L-R asymmetry.

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Posted May 17, 2018.
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Presence of midline cilia supersedes the expression of Lefty1 in forming the midline barrier during the establishment of left-right asymmetry
Natalia A Shylo, Dylan Ramrattan, Scott D Weatherbee
bioRxiv 324533; doi: https://doi.org/10.1101/324533
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Presence of midline cilia supersedes the expression of Lefty1 in forming the midline barrier during the establishment of left-right asymmetry
Natalia A Shylo, Dylan Ramrattan, Scott D Weatherbee
bioRxiv 324533; doi: https://doi.org/10.1101/324533

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