SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation
Abstract Background Polarity is necessary for epithelial cells to perform distinct functions at their apical and basal surfaces. Oral epithelial cell-derived ameloblasts at secretory stage (SABs) synthesize large amounts of enamel matrix proteins (EMPs), largely amelogenins. EMPs are unidirectionall...
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| Language: | English |
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BMC
2019-12-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-019-0722-9 |
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| author | Yan Zhang Liwei Zheng Michael Le Yukiko Nakano Barry Chan Yulei Huang Parisa Moravedje Torbaty Yoshinori Kohwi Ralph Marcucio Stefan Habelitz Pamela K. Den Besten Terumi Kohwi-Shigematsu |
| author_facet | Yan Zhang Liwei Zheng Michael Le Yukiko Nakano Barry Chan Yulei Huang Parisa Moravedje Torbaty Yoshinori Kohwi Ralph Marcucio Stefan Habelitz Pamela K. Den Besten Terumi Kohwi-Shigematsu |
| author_sort | Yan Zhang |
| collection | DOAJ |
| description | Abstract Background Polarity is necessary for epithelial cells to perform distinct functions at their apical and basal surfaces. Oral epithelial cell-derived ameloblasts at secretory stage (SABs) synthesize large amounts of enamel matrix proteins (EMPs), largely amelogenins. EMPs are unidirectionally secreted into the enamel space through their apical cytoplasmic protrusions, or Tomes’ processes (TPs), to guide the enamel formation. Little is known about the transcriptional regulation underlying the establishment of cell polarity and unidirectional secretion of SABs. Results The higher-order chromatin architecture of eukaryotic genome plays important roles in cell- and stage-specific transcriptional programming. A genome organizer, special AT-rich sequence-binding protein 1 (SATB1), was discovered to be significantly upregulated in ameloblasts compared to oral epithelial cells using a whole-transcript microarray analysis. The Satb1 −/− mice possessed deformed ameloblasts and a thin layer of hypomineralized and non-prismatic enamel. Remarkably, Satb1 −/− ameloblasts at the secretory stage lost many morphological characteristics found at the apical surface of wild-type (wt) SABs, including the loss of Tomes’ processes, defective inter-ameloblastic adhesion, and filamentous actin architecture. As expected, the secretory function of Satb1 −/− SABs was compromised as amelogenins were largely retained in cells. We found the expression of epidermal growth factor receptor pathway substrate 8 (Eps8), a known regulator for actin filament assembly and small intestinal epithelial cytoplasmic protrusion formation, to be SATB1 dependent. In contrast to wt SABs, EPS8 could not be detected at the apical surface of Satb1 −/− SABs. Eps8 expression was greatly reduced in small intestinal epithelial cells in Satb1 −/− mice as well, displaying defective intestinal microvilli. Conclusions Our data show that SATB1 is essential for establishing secretory ameloblast cell polarity and for EMP secretion. In line with the deformed apical architecture, amelogenin transport to the apical secretory front and secretion into enamel space were impeded in Satb1 −/− SABs resulting in a massive cytoplasmic accumulation of amelogenins and a thin layer of hypomineralized enamel. Our studies strongly suggest that SATB1-dependent Eps8 expression plays a critical role in cytoplasmic protrusion formation in both SABs and in small intestines. This study demonstrates the role of SATB1 in the regulation of amelogenesis and the potential application of SATB1 in ameloblast/enamel regeneration. |
| first_indexed | 2024-12-17T05:30:12Z |
| format | Article |
| id | doaj.art-6ee563e0973f44dfa299a51ff24264f9 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-17T05:30:12Z |
| publishDate | 2019-12-01 |
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| spelling | doaj.art-6ee563e0973f44dfa299a51ff24264f92022-12-21T22:01:45ZengBMCBMC Biology1741-70072019-12-0117111610.1186/s12915-019-0722-9SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formationYan Zhang0Liwei Zheng1Michael Le2Yukiko Nakano3Barry Chan4Yulei Huang5Parisa Moravedje Torbaty6Yoshinori Kohwi7Ralph Marcucio8Stefan Habelitz9Pamela K. Den Besten10Terumi Kohwi-Shigematsu11Department of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orthopaedic Surgery, University of CaliforniaPreventive and Restorative Dental Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaDepartment of Orofacial Sciences, University of CaliforniaAbstract Background Polarity is necessary for epithelial cells to perform distinct functions at their apical and basal surfaces. Oral epithelial cell-derived ameloblasts at secretory stage (SABs) synthesize large amounts of enamel matrix proteins (EMPs), largely amelogenins. EMPs are unidirectionally secreted into the enamel space through their apical cytoplasmic protrusions, or Tomes’ processes (TPs), to guide the enamel formation. Little is known about the transcriptional regulation underlying the establishment of cell polarity and unidirectional secretion of SABs. Results The higher-order chromatin architecture of eukaryotic genome plays important roles in cell- and stage-specific transcriptional programming. A genome organizer, special AT-rich sequence-binding protein 1 (SATB1), was discovered to be significantly upregulated in ameloblasts compared to oral epithelial cells using a whole-transcript microarray analysis. The Satb1 −/− mice possessed deformed ameloblasts and a thin layer of hypomineralized and non-prismatic enamel. Remarkably, Satb1 −/− ameloblasts at the secretory stage lost many morphological characteristics found at the apical surface of wild-type (wt) SABs, including the loss of Tomes’ processes, defective inter-ameloblastic adhesion, and filamentous actin architecture. As expected, the secretory function of Satb1 −/− SABs was compromised as amelogenins were largely retained in cells. We found the expression of epidermal growth factor receptor pathway substrate 8 (Eps8), a known regulator for actin filament assembly and small intestinal epithelial cytoplasmic protrusion formation, to be SATB1 dependent. In contrast to wt SABs, EPS8 could not be detected at the apical surface of Satb1 −/− SABs. Eps8 expression was greatly reduced in small intestinal epithelial cells in Satb1 −/− mice as well, displaying defective intestinal microvilli. Conclusions Our data show that SATB1 is essential for establishing secretory ameloblast cell polarity and for EMP secretion. In line with the deformed apical architecture, amelogenin transport to the apical secretory front and secretion into enamel space were impeded in Satb1 −/− SABs resulting in a massive cytoplasmic accumulation of amelogenins and a thin layer of hypomineralized enamel. Our studies strongly suggest that SATB1-dependent Eps8 expression plays a critical role in cytoplasmic protrusion formation in both SABs and in small intestines. This study demonstrates the role of SATB1 in the regulation of amelogenesis and the potential application of SATB1 in ameloblast/enamel regeneration.https://doi.org/10.1186/s12915-019-0722-9AmeloblastEnamelSpecial AT-rich sequence-binding protein-1 (SATB1)AmelogeninClaudin 1Tight junction |
| spellingShingle | Yan Zhang Liwei Zheng Michael Le Yukiko Nakano Barry Chan Yulei Huang Parisa Moravedje Torbaty Yoshinori Kohwi Ralph Marcucio Stefan Habelitz Pamela K. Den Besten Terumi Kohwi-Shigematsu SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation BMC Biology Ameloblast Enamel Special AT-rich sequence-binding protein-1 (SATB1) Amelogenin Claudin 1 Tight junction |
| title | SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation |
| title_full | SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation |
| title_fullStr | SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation |
| title_full_unstemmed | SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation |
| title_short | SATB1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation |
| title_sort | satb1 establishes ameloblast cell polarity and regulates directional amelogenin secretion for enamel formation |
| topic | Ameloblast Enamel Special AT-rich sequence-binding protein-1 (SATB1) Amelogenin Claudin 1 Tight junction |
| url | https://doi.org/10.1186/s12915-019-0722-9 |
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