Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation.
The authors declare no competing or financial interests.
K.M.B. designed and conducted experiments and analyzed data, with assistance and supervision from S.E.W. K.J.L. and T.A.C. oversaw management of the mouse facility and performed lentiviral injections. K.J.L. assisted in making lentivirus, aided in experimental design and analysis, and conceptualized the application and analysis of the radial heat maps. J.H.P. assisted with performing experiments, image acquisition and data analysis. C.P.D. performed analysis of LGN fluorescence intensity. S.E.W. and K.M.B. wrote the manuscript, with input from all authors.
K.M.B. is supported by a National Institutes of Health T90 Training Grant [NIH/NIDCR 5T90DE021986-05] and NIH Loan Repayment Plan [NOT-OD-15-122]. S.E.W. is supported by a Kimmel Scholar Award [SKF-15-065] from the Sidney Kimmel Foundation for Cancer Research and an IBM Junior Faculty Development Award. Deposited in PMC for release after 12 months.
Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.136010.supplemental
- Received February 3, 2016.
- Accepted June 6, 2016.