Abstract
Four and a half LIM domains 2 (FHL2) functions as a transcriptional co-activator or co-repressor in a cell-type-specific manner. As a positive regulator, FHL2 plays an important role in osteoblast differentiation and bone formation. Our previous study showed that FHL2 was expressed in odontoblasts in mature human teeth under normal and pathological conditions. The purpose of this study was to investigate the spatial-temporal expression patterns of FHL2 at different stages of mouse molar development by immunohistochemistry. Our results showed that at the bud and cap stage, FHL2 was expressed both in enamel organ and the underlying mesenchyme. At the early bell stage, FHL2 appeared in the inner and outer enamel epithelium, stratum intermedium and the secondary enamel knot. Positive staining gradually converged at the cusps of dental papilla. At the late bell stage, FHL2 was expressed in the terminal differentiated ameloblasts and odontoblasts and stratum intermedium. At the postnatal day, FHL2 was detected in the secretory and mature ameloblasts and odontoblasts and mature enamel, and gradually appeared at Hertwig’s epithelial root sheath and periodontal tissues. The spatial-temporal expression patterns of FHL2 from the bud stage to the postnatal day (13.5) suggested that during tooth development, FHL2 might play an important role in ameloblast and odontoblast differentiation, secretion of enamel and dentin matrix, mineralization of enamel, molar crown morphogenesis, as well as root formation.
Similar content being viewed by others
References
Amaar YG, Thompson GR, Linkhart TA, Chen ST, Baylink DJ, Mohan S (2002) Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2). J Biol Chem 277:12053–12060
Bai S, Kitaura H, Zhao H, Chen J, Müller JM, Schüle R, Darnay B, Novack DV, Ross FP, Teitelbaum SL (2005) FHL2 inhibits the activated osteoclast in a TRAF6-dependent manner. J Clin Invest 115:2742–2751
Chan KK, Tsui SK, Lee SM, Luk SC, Liew CC, Fung KP, Waye MM, Lee CY (1998) Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart. Gene 210:345–350
Chen J, Lan Y, Baek JA, Gao Y, Jiang R (2009) Wnt/beta-catenin signaling plays an essential role in activation of odontogenic mesenchyme during early tooth development. Dev Biol 334:174–185
Cho SW, Lee HA, Cai J, Lee MJ, Kim JY, Ohshima H, Jung HS (2007) The primary enamel knot determines the position of the first buccal cusp in developing mice molars. Differentiation 75:441–451
Chu PH, Ruiz-Lozano P, Zhou Q, Cai C, Chen J (2000) Expression patterns of FHL/SLIM family members suggest important functional roles in skeletal muscle and cardiovascular system. Mech Dev 95:259–265
Diekwisch TG (2001) The development biology of cementum. Int J Dev Biol 45:695–706
Fang P, Wang X, Zhang L, Yuan G, Chen Z, Zhang Q (2010) Immunohistochemical localization of LIM mineralization protein 1 during mouse molar development. J Mol Histol 41:199–203
Genini M, Schwalbe P, Scholl FA, Remppis A, Mattei MG, Schäfer BW (1997) Subtractive cloning and characterization of DRAL, a novel LIM-domain protein down-regulated in rhabdomyosarcoma. DNA Cell Biol 16:433–442
Govoni KE, Amaar YG, Kramer A, Winter E, Baylink DJ, Mohan S (2006a) Regulation of insulin-like growth factor binding protein-5, four and a half lim-2, and a disintegrin and metalloprotease-9 expression in osteoblasts. Growth Horm IGF Res 16:49–56
Govoni KE, Baylink DJ, Chen J, Mohan S (2006b) Disruption of four-and-a-half LIM2 decrease bone mineral content and bone mineral density in femur and tibia bones of female mice. Calcif Tissue Int 79:112–117
Günther T, Poli C, Müller JM, Catala-Lehnen P, Schinke T, Yin N, Vomstein S, Amling M, Schüle R (2005) Fhl2 deficiency results in osteopenia due to decreased activity of osteoblasts. EMBO J 24:3049–3056
Hamidouche Z, Haÿ E, Vaudin P, Charbord P, Schüle R, Marie PJ, Fromigué O (2008) FHL2 mediates dexamethasone-induced mesenchymal cell differentiation into osteoblasts by activating Wnt/beta-catenin signaling-dependent Runx2 expression. FASEB J 22:3813–3822
Honda JY, Kobayashi I, Kiyoshima T, Nagata K, Wada H, Ookuma Y, Fujiwara H, Shiotsuka M, Takahashi I, Sakai H (2011) In situ expression of the mitochondrial ATPase6 gene in the developing tooth germ of the mouse lower first molar. J Mol Histol 42:83–90
Jernvall J, Thesleff I (2000) Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev 92:19–29
Kavanagh KD, Evans AR, Jernvall J (2007) Predicting evolutionary patterns of mammalian teeth from development. Nature 449:427–432
Lai CF, Bai S, Uthgenannt BA, Halstead LR, Mcloughlin P, Schafer BW, Chu PH, Chen J, Otey CA, Cao X, Cheng SL (2006) Four and half lim protein 2 (FHL2) stimulates osteoblast differentiation. J Bone Miner Res 21:17–28
Li L, Yuan G, Liu C, Zhang L, Zhang Y, Chen Y, Chen Z (2011) Exogenous fibroblast growth factor 8 rescues development of mouse diastema vestigial tooth ex vivo. Dev Dyn 240:1344–1353
Matalova E, Antonarakis GS, Sharpe PT, Tucker AS (2005) Cell lineage of primary and secondary enamel knots. Dev Dyn 233:754–759
McLoughlin P, Ehler E, Carlile G, Licht JD, Schäfer BW (2002) The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein. J Biol Chem 277:37045–37053
Morlon A, Sassone-Corsi P (2003) The LIM-only protein FHL2 is a serum-inducible transcriptional coactivator of AP-1. Proc Natl Acad Sci USA 100:3977–3982
Müller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schüle R (2000) FHL2, a novel tissue-specific coactivator of the androgen receptor. EMBO J 19:359–369
Owens PD (1978) Ultrastructure of Hertwig’s epithelial root sheath during early root development in premolar teeth in dogs. Arch Oral Biol 23:91–104
Pispa J, Thesleff I (2003) Mechanisms of ectodermal organogenesis. Dev Biol 262:195–205
Ruch JV, Lesot H, Begue-Kirn C (1995) Odontoblast differentiation. Int J Dev Biol 39:51–68
Thesleff I (2003) Epithelial-mesenchymal signaling regulating tooth morphogenesis. J Cell Sci 116:1647–1648
Thesleff I, Keränen S, Jernvall J (2001) Enamel knots as signaling centers linking tooth morphogenesis and odontoblast differentiation. Adv Dent Res 15:14–18
Thomas HF (1995) Root formation. Int J Dev Biol 39:231–237
Vaahtokari A, Aberg T, Jernvall J, Keränen S, Thesleff I (1996) The enamel knot as a signaling center in the developing mouse tooth. Mech Dev 54:39–43
Viriot L, Peterková R, Vonesch JL, Peterka M, Ruch JV, Lesot H (1997) Mouse molar morphogenesis revisited by three-dimensional reconstruction. III. Spatial distribution of mitoses and apoptosis up to bell-staged first lower molar teeth. Int J Dev Biol 41:679–690
Wang J, Yang Y, Xia HH, Gu Q, Lin MC, Jiang B, Peng Y, Li G, An X, Zhang Y, Zhuang Z, Zhang Z, Kung HF, Wong BC (2007) Suppression of FHL2 expression induces cell differentiation and inhibits gastric and colon carcinogenesis. Gastroenterology 132:1066–1076
Wang X, Wang Q, Wang L, Yang P (2011) Immunohistochemical localization of four and a half LIM domains 2 in the odontoblasts of mature human teeth. J Mol Histol 42:97–103
Wei Y, Renard CA, Labalette C, Wu Y, Lévy L, Neuveut C, Prieur X, Flajolet M, Prigent S, Buendia MA (2003) Identification of the LIM protein FHL2 as a coactivator of beta-catenin. J Biol Chem 278:5188–5194
Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M (2000) The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes. J Biol Chem 275:33669–33678
Yamashiro T, Åberg T, Levanon D, Groner Y, Thesleff I (2002) Expression of Runx1, -2 and -3 during tooth, palate and craniofacial bone development. Mech Dev 119:107–110
Zeichner-David M, Diekwisch T, Fincham A, Lau E, MacDougall M, Moradian-Oldak J, Simmer J, Snead M, Slavkin HC (1995) Control of ameloblast differentiation. Int J Dev Biol 39:69–92
Acknowledgments
This work was supported by the National Natural Science Foundation of China (grant No.30901673), Specialized Research Fund for the Doctoral Program of Higher Education of China (grant no.20090131120059), China Postodoctoral Science Foundation Funded Project (grant no.200902565).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Xiaoying Wang and Pishan Yang are the co-corresponding author and equal contribution to this study.
Rights and permissions
About this article
Cite this article
Du, J., Wang, Q., Wang, L. et al. The expression pattern of FHL2 during mouse molar development. J Mol Hist 43, 289–295 (2012). https://doi.org/10.1007/s10735-012-9409-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-012-9409-z