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 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.
Highlights
A main function of tear flow is to lubricate ocular surface preventing it from drying
We further show a general role of Prickle 1 in regulation of polarized secretion and deposition of basement membrane (BM) in tear drainage system and embryoid body (EB) organoids, which is likely independent of establishment of apicobasal polarity
Tear duct origin and the timings of crucial events during development To gain developmental insights into tear drainage system, we first determined when tear duct initiates by performing 3D-reconstruction of primordial tear duct (PTD) at embryonic day 11 (E11) using iDISCO technology 31 (Fig. 1A, Supplemental movie 1)
Summary
A main function of tear flow is to lubricate ocular surface preventing it from drying. Prickle 1 is a hallmark for tear duct ontogenesis We investigated whether Wnt/PCP signaling components, which play essential roles in tubulogenesis in a variety of tissue contexts, were expressed in PTD using in situ hybridization. Prickle 1 was found strongly expressed in initiating/primordial tear duct at E11 on parasagittal sections (Fig. 2A-C, green).
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