LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development.
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.
Department of Pathology & Laboratory Medicine and Department of Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
Kevin M
0000-0002-5565-0524
KM
Byrd
Department of Pathology & Laboratory Medicine and Department of Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
Kendall J
KJ
Lough
Department of Pathology & Laboratory Medicine and Department of Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
Jeet H
JH
Patel
Department of Pathology & Laboratory Medicine and Department of Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
Carlos Patiño
CP
Descovich
Department of Pathology & Laboratory Medicine and Department of Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA.
T Anthony
TA
Curtis
Department of Pathology & Laboratory Medicine and Department of Biology, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7525, USA scott_williams@med.unc.edu.
Scott E
0000-0001-9975-7334
SE
Williams
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004848:Epithelium / Q000378:metabolism*; D018859:Hair Follicle / Q000196:embryology* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008855:Microscopy, Electron, Scanning; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013650:Taste Buds / Q000196:embryology / Q000378:metabolism; D014059:Tongue / Q000196:embryology / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C502655:LGN protein, mouse
Gpsm2; Hair follicle; LGN; Oral epithelia; Oriented cell divisions; Papillae; Placode; Tongue