NFIB regulates embryonic development of submandibular glands.
NFIB (nuclear factor I B) is a NFI transcription factor family member, which is essential for the development of a variety of organ systems. Salivary gland development occurs through several stages, including prebud, bud, pseudoglandular, canalicular, and terminal. Although many studies have been done to understand mouse submandibular gland (SMG) branching morphogenesis, little is known about SMG cell differentiation during the terminal stages. The goal of this study was to determine the role of NFIB during SMG development. We analyzed SMGs from wild-type and Nfib-deficient mice (Nfib (-/-)). At embryonic (E) day 18.5, SMGs from wild-type mice showed duct branching morphogenesis and differentiation of tubule ductal cells into tubule secretory cells. In contrast, SMGs from Nfib (-/-) mice at E18.5 failed to differentiate into tubule secretory cells while branching morphogenesis was unaffected. SMGs from wild-type mice at E16.5 displayed well-organized cuboidal inner terminal tubule cells. However, SMGs from Nfib (-/-) at E16.5 displayed disorganized inner terminal tubule cells. SMGs from wild-type mice at E18.5 became fully differentiated, as indicated by a high degree of apicobasal polarization (i.e., presence of apical ZO-1 and basolateral E-cadherin) and columnar shape. Furthermore, SMGs from wild-type mice at E18.5 expressed the protein SMGC, a marker for tubule secretory cells. However, SMGs from Nfib (-/-) mice at E18.5 showed apicobasal polarity, but they were disorganized and lost the ability to secrete SMGC. These findings indicate that the transcription factor NFIB is not required for branching morphogenesis but plays a key role in tubule cell differentiation during mouse SMG development.
School of Dentistry University of Utah, Salt Lake City, UT, USA.
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Mellas
Department of Restorative Dentistry, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, USA.
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Kim
Department of Biochemistry, Developmental Genomics Group, Center of Excellence in Bioinformatics and Life Science, University at Buffalo, The State University of New York, Buffalo, NY, USA.
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J
Osinski
Department of Restorative Dentistry, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, USA.
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Sadibasic
Department of Biochemistry, Developmental Genomics Group, Center of Excellence in Bioinformatics and Life Science, University at Buffalo, The State University of New York, Buffalo, NY, USA.
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Gronostajski
Department of Oral Biology, School of Dental Medicine, University at Buffalo, The State University of New York, Buffalo, NY, USA.
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Cho
School of Dentistry University of Utah, Salt Lake City, UT, USA olga.baker@hsc.utah.edu.
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Baker
D000818:Animals; D051402:Aquaporin 5 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D048430:Cell Shape; D047108:Embryonic Development; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009024:Morphogenesis / Q000502:physiology; D009077:Mucins / Q000032:analysis; D051839:NFI Transcription Factors / Q000235:genetics / Q000502:physiology*; D018987:Salivary Ducts / Q000166:cytology / Q000196:embryology; D013363:Submandibular Gland / Q000166:cytology / Q000196:embryology*; D062826:Zonula Occludens-1 Protein / Q000032:analysis
C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D015415:Biomarkers; D015820:Cadherins; D009077:Mucins; D051839:NFI Transcription Factors; C484683:Nfib protein, mouse; C491421:Smgc protein, mouse; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein
cells; differentiation; epithelium; morphogenesis; salivary glands; transcription factors