The axiom “a place for everything, and everything in its place” epitomizes the intricate design of the body. This is exemplified in patients with heterotaxy, a developmental defect characterized by the abnormal arrangement of major organs, with serious health consequences.
Left-right patterning during embryonic development has been attributed to the beating of cilia—eyelash-like protrusions from the cell surface—in a specialized region of embryos called the node. During fetal development, these cilia beat with distinct patterns to other types of cilia, such as those in the trachea that clear mucus from the airways. However, the molecular mechanisms that regulate these beat patterns have remained obscure.
“In each instance, the cilia involved are adapted to provide the correct hydrodynamic forces for the function in question,” explained Sudipto Roy, a Senior Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB), whose research team is interested in understanding how specific cellular proteins influence cilia motility.
Roy and his colleagues had previously found that a protein called CFAP53 controlled the beating of human cilia in the node region, influencing the left-right organization of visceral organs. In their latest study, Roy collaborated with Hiroshi Hamada of RIKEN Centre for Biosystems Dynamics Research to further explore how CFAP53 controls the function and motility of cilia present in both the node and trachea.
Using advanced genetic and cell biology techniques, the researchers found that, much like in other species such as humans and zebrafish, the loss of CFAP53 resulted in heterotaxy in mice, a condition in which the location of major organs are mirrored. Interestingly, cilia in mice lacking CFAP53 were immotile in the node but not the trachea, indicating the specific role of this protein in fetal development.
Additionally, Roy and colleagues found strikingly different distributions of CFAP53 in the embryonic cilia versus the ones in the trachea—another novel insight that could explain their motility differences.
“CFAP53 can interact with dynein proteins that drive ciliary motility and proteins like TTC25 that help to anchor the dyneins to ciliary microtubules,” Roy explained. “CFAP53 localizes to the ciliary basal body as well as to the ciliary microtubules to facilitate the transport of dyneins and dynein anchoring proteins and to anchor them on ciliary microtubules, respectively.”
Roy added that the team is continuing to explore the cell processes governed by CFAP53 and will collaborate with clinicians to better understand how CFAP53 mutations can impact patients.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology (IMCB).
