Ontogenesis of the tear drainage system requires Prickle 1-driven polarized basement membrane (BM) deposition

Abstract

In terrestrial animals, the lacrimal drainage apparatus evolved to serve as conduits for tear flow; however, little is known about the ontogenesis of this system. Here, we defined the anatomy of the fully formed tear duct (TD) in mice, characterized crucial morphogenetic events for the development of tear duct components, and identified the site for primordial tear duct (PTD) initiation. We report that the PTD originates from the orbital lacrimal lamina (LL), a junction formed by the epithelia of the maxillary (mxp) and lateral nasal processes (lnp). We demonstrate that Prickle 1, a key component of planar cell polarity (PCP) signaling, is expressed in progenitors of the PTD and throughout tear duct morphogenesis. Disruption of Prickle 1 stalls tear duct elongation; in particular, the loss of basement membrane (BM) deposition and aberrant cytoplasmic accumulation of laminin are salient. Altered cell adhesion, cytoskeletal and vesicular transport systems, and cell axis orientation in Prickle 1 mutants support the role of Prickle 1 in PCP. Taken together, we highlight a crucial role of Prickle 1-mediated polarized BM secretion and deposition in PTD elongation.