Ontogenesis of the tear drainage system requires Prickle1-driven polarized basement membrane deposition

ABSTRACTIn 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 define the anatomy of the fully formed tear duct in mice, characterize crucial morphogenetic events for the development of tear duct components and identify the site for primordial tear duct (PTD) initiation. We report that the PTD originates from the orbital lacrimal lamina, a junction formed by the epithelia of the maxillary and lateral nasal processes. We demonstrate that Prickle1, a key component of planar cell polarity signaling, is expressed in progenitors of the PTD and throughout tear duct morphogenesis. Disruption of Prickle1 stalls tear duct elongation; in particular, the loss of basement membrane deposition and aberrant cytoplasmic accumulation of laminin are salient. Altered cell adhesion, cytoskeletal transport systems, vesicular transport systems and cell axis orientation in Prickle1 mutants support the role of Prickle1 in planar cell polarity. Taken together, our results highlight a crucial role of Prickle1-mediated polarized basement membrane secretion and deposition in PTD elongation.

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

10.1101/2020.04.07.029793 ◽

2020 ◽

Author(s):

Dianlei Guo ◽

Jiali Ru ◽

Fuxiang Mao ◽

Kaili Wu ◽

Hong Ouyang ◽

...

Keyword(s):

Basement Membrane ◽

Protein Trafficking ◽

Drainage System ◽

Embryoid Bodies ◽

Apicobasal Polarity ◽

Tear Flow ◽

Cytoplasmic Accumulation ◽

High Level ◽

Lacrimal Drainage

AbstractIn 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.

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