Left–Right Patterning: Breaking Symmetry to Asymmetric Morphogenesis

• Published in: Trends in genetics 2017-09, Vol.33 (9), p.616-628
• Main Authors: Grimes, Daniel T., Burdine, Rebecca D.
• Format: Article
• Language: English
• Subjects: Animals; Body Patterning; cell migration; cilia; left–right asymmetry; Morphogenesis; Nodal; Pitx2
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2017.06.004

Vertebrates exhibit striking left–right (L–R) asymmetries in the structure and position of the internal organs. Symmetry is broken by motile cilia-generated asymmetric fluid flow, resulting in a signaling cascade – the Nodal–Pitx2 pathway – being robustly established within mesodermal tissue on the left side only. This pathway impinges upon various organ primordia to instruct their side-specific development. Recently, progress has been made in understanding both the breaking of embryonic L–R symmetry and how the Nodal–Pitx2 pathway controls lateralized cell differentiation, migration, and other aspects of cell behavior, as well as tissue-level mechanisms, that drive asymmetries in organ formation. Proper execution of asymmetric organogenesis is critical to health, making furthering our understanding of L–R development an important concern. Gut looping morphogenesis depends on Nodal–Pitx2 pathway-induced changes to the cellular architecture of the dorsal mesentery coupled with physical forces imparted on the gut by the dorsal mesentery. In zebrafish, gut asymmetries are driven by asymmetric migration of the lateral plate mesoderm, which pushes the gut tube away from the midline. Early cardiac asymmetries depend on Nodal signaling-induced asymmetries in cardiac progenitor cell migration. Cardiac looping asymmetry is driven by forces intrinsic to the heart but made robust by external Nodal pathway cues. Asymmetric migration of the parapineal in the zebrafish brain is achieved by an integration of FGF and Nodal signals, which drive migration and bias the direction, respectively.