Spatio-temporal regulation of the planar cell polarity (PCP) and apico-basal (A-B) polarity signalings plays important roles in the formation and maintenance of the epithelial tubular structures. Disruption of a proper balance between PCP and A-B polarity signalings is assumed to result in the breakdown of the epithelial tissues and/or induction of epithelial-mesenchymal transition, Thus, it is of importance to clarify how these two signalings interact or cooperate to achieve proper outcomes. The cilium localized at apical surface of the epithelial cells also plays an essential role in the formation and maintenance of the epithelial structures by acting as signaling center, and its structural and/or functional abnormalities are related to so-called ciliopathies.

In this project, we first aim to clarify the molecular bases of PCP signaling and cilia-mediated signaling during the formation and maintenance of the epithelial tubular structures. More importantly, we challenge to elucidate the relationship between the abnormalities of these signalings and pathological conditions, including ciliopathies, inflammation, cancer invasion/metastasis, and developmental anomalies by employing signaling perturbation methods at cell, tissue, and organ levels.

In this project, we focus on PCP and cilia-mediated signalings, and their implications in ciliopathies and cancer invasion/metastasis. To achieve our research purpose, we try to clarify the molecular bases of these signalings mediated by soluble factors, their cognate receptors, and adaptor molecules and so on. We will also perform signaling perturbation experiments by using in vitro 3D culture and organ culture to elucidate the relationship between the disruption of PCP and cilia-mediated signalings in various pathological conditions. Moreover, we establish and analyze mutant mice, lacking expression of various components of PCP and cilia-mediated signalings at particular cell-types and tissues as in vivo disease models. Throughout our research project, we collaborate actively with other members of the entire project to open a way to establish a new research field, Tubulology.

This research project will unravel the molecular mechanisms of PCP/A-B polarity signalings and cilia-mediated signaling which play crucial roles in the formation and maintenance of the epithelial tubular structures. Since different types of the epithelial tissues and organs are our research objects, it is also expected to clarify the molecular and cellular bases of tissue- and organ-specific machineries of the epithelial tissue formation. Our pathological approaches, based on signaling perturbation experiments both in vitro and in vivo, will shed light on our understanding of various diseases, including ciliopathies, inflammation, cancer progression, and developmental anomalies. The outcome of this project will also contribute to develop a novel therapeutic approach for various inflammation and cancers.