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

Abstract

In terrestrial animals, lacrimal drainage apparatus evolved to serve as conduits for tear flow. Little is known about the ontogenesis of this system. Here, we investigated tear duct origin, developmental course, genetic and cellular determinants in mouse. We report that primordial tear duct (PTD) originates from junction epithelium of the joining maxillary and lateral nasal processes, which reshapes into future tear duct branches. We identified Prickle 1 as a hallmark for tear duct outgrowth, ablation of which stalled duct elongation. In particular, the disruption of basement membrane (BM) with cytoplasmic accumulation of laminin suggests aberrant protein trafficking. Mutant embryoid bodies (EBs) derived from iPSCs recapitulate BM phenotype of the PTD exhibiting defective visceral endoderm (VE), which normally expresses high level of Prickle 1. Furthermore, replenishing mutant VE with Prickle 1 completely rescued BM but not cell polarity. Taken together, our results reveal a distinct role of Prickle 1 in regulating polarized BM secretion and deposition in precedently uncharacterized tear drainage system and VE, which is independent of apicobasal polarity establishment.

Malformation of Tear Ducts Underlies the Epiphora and Precocious Eyelid Opening inPrickle 1Mutant Mice: Genetic Implications for Tear Duct Genesis

“…10 In contrast, both the rat and mouse NLD initiate from the nasolacrimal groove as the human does. 9,10,47,48 Thus, it appears that the similarity in tear duct development among species does not necessarily reflect the similarity of the tear duct physiology. Genetically, Prickle 1 expression in both human and mouse tear ducts implies its evolutionarily assigned molecular function in this organ.…”