Cilia in vertebrate left-right patterning.
Understanding how left-right (LR) asymmetry is generated in vertebrate embryos is an important problem in developmental biology. In humans, a failure to align the left and right sides of cardiovascular and/or gastrointestinal systems often results in birth defects. Evidence from patients and animal models has implicated cilia in the process of left-right patterning. Here, we review the proposed functions for cilia in establishing LR asymmetry, which include creating transient leftward fluid flows in an embryonic 'left-right organizer'. These flows direct asymmetric activation of a conserved Nodal (TGFβ) signalling pathway that guides asymmetric morphogenesis of developing organs. We discuss the leading hypotheses for how cilia-generated asymmetric fluid flows are translated into asymmetric molecular signals. We also discuss emerging mechanisms that control the subcellular positioning of cilia and the cellular architecture of the left-right organizer, both of which are critical for effective cilia function during left-right patterning. Finally, using mosaic cell-labelling and time-lapse imaging in the zebrafish embryo, we provide new evidence that precursor cells maintain their relative positions as they give rise to the ciliated left-right organizer. This suggests the possibility that these cells acquire left-right positional information prior to the appearance of cilia.This article is part of the themed issue 'Provocative questions in left-right asymmetry'.
Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Agnik
A
Dasgupta
Department of Cell and Developmental Biology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA amackj@upstate.edu.
Jeffrey D
0000-0002-5465-9754
JD
Amack
D000818:Animals; D019521:Body Patterning; D002923:Cilia / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055457:Nodal Protein / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014714:Vertebrates / Q000196:embryology* / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D055457:Nodal Protein; D029961:Zebrafish Proteins
birth defects; fluid flow dynamics; left–right asymmetry; mechanosensory cilia; motile cilia