Skip to main content

Advertisement

Log in

Modulation of cell proliferation during palatogenesis by the interplay between Tbx3 and Bmp4

  • Short communication
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

During secondary palate development, two shelves are elevated to a horizontal position above the tongue through a process involving many cellular mechanisms, including proliferation. In particular, the expression patterns of Tbx3 and Bmp4, which are colocalized at embryonic day 13.5 (E13.5) and have unique expression patterns in specific regions at E14.5, have been investigated in early mouse palatogenesis. Tbx3 expression is reported to be associated with Bmp4 signaling during the process of organogenesis in other areas, such as limb development. However, the function of Tbx3 and the relationship between Tbx3 and Bmp4 in palate development have not been determined. We have examined the gene expression pattern and cell proliferation in order to understand the mutual interactions and function of Tbx3 and Bmp4. An electroporation method was used to investigate the altered pattern of these genes after their over-expression in organ cultures. NOGGIN protein-soaked beads were also implanted into the cultured palate to determine the function of Bmp4 in palatogenesis. After electroporation and NOGGIN bead implantation, the number of PCNA-positive cells was counted. The results showed that Tbx3 and Bmp4 strongly up- and down-regulated each other in order to control the proliferation of the palatal shelf. Thus, Tbx3 expression is induced by Bmp4 in the mesenchyme of the anterior palatal shelves, whereas mesenchymal expression of Tbx3 down-regulates Bmp4 expression in the mesenchyme of the palate. The harmonization between Tbx3 and Bmp4 therefore controls cell proliferation to regulate secondary palate development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  • Alappat SR, Zhang Z, Chen Y (2003) Msx homeobox gene family and craniofacial development. Cell Res 13:429–442

    Article  PubMed  CAS  Google Scholar 

  • Bitgood MJ, McMahon AP (1995) Hedgehog and Bmp genes are coexpressed at many diverse sites of cell-cell interaction in the mouse embryo. Dev Biol 172:126–138

    Article  PubMed  CAS  Google Scholar 

  • Brummelkamp TR, Kortlever RM, Lingbeek M, Trettel F, MacDonald ME, Lohuizen M van, Bernards R (2002) TBX-3, the gene mutated in ulnar-mammary syndrome, is a negative regulator of p19ARF and inhibits senescence. J Biol Chem 277:6567–6572

    Article  PubMed  CAS  Google Scholar 

  • Chou MJ, Kosazuma T, Takigawa T, Yamada S, Takahara S, Shiota K (2004) Palatal shelf movement during palatogenesis: a fate map of the fetal mouse palate cultured in vitro. Anat Embryol (Berl) 208:19–25

    Article  Google Scholar 

  • Davenport TG, Jerome-Majewska LA, Papaioannou VE (2003) Mammary gland, limb and yolk sac defects in mice lacking Tbx3, the gene mutated in human ulnar mammary syndrome. Development 130:2263–2273

    Article  PubMed  CAS  Google Scholar 

  • Francis-West P, Ladher R, Barlow A, Graveson A (1998) Signalling interactions during facial development. Mech Dev 75:3–28

    Article  PubMed  CAS  Google Scholar 

  • Gibson-Brown JJ, Agulnik SI, Silver LM, Papaioannou VE (1998) Expression of T-box genes Tbx2-Tbx5 during chick organogenesis. Mech Dev 74:165–169

    Article  PubMed  CAS  Google Scholar 

  • Govoni KE, Lee SK, Chadwick RB, Yu H, Kasukawa Y, Baylink DJ, Mohan S (2006) Whole genome microarray analysis of growth hormone-induced gene expression in bone: T-box3, a novel transcription factor, regulates osteoblast proliferation. Am J Physiol Endocrinol Metab 291:E128–E136

    Article  PubMed  CAS  Google Scholar 

  • Hilliard SA, Yu L, Gu S, Zhang Z, Chen YP (2005) Regional regulation of palatal growth and patterning along the anterior-posterior axis in mice. J Anat 207:655–667

    PubMed  Google Scholar 

  • Ito A, Asamoto M, Hokaiwado N, Takahashi S, Shirai T (2005) Tbx3 expression is related to apoptosis and cell proliferation in rat bladder both hyperplastic epithelial cells and carcinoma cells. Cancer Lett 219:105–112

    Article  PubMed  CAS  Google Scholar 

  • Jacobs JJL, Keblusek P, Robanus-Maandag E, Kristel P, Lingbeek M, Nederlof PM, Welsem T van, Vijver MJ van de, Koh EY, Daley GQ, Lohuizen M van (2000) Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19ARF) and is amplified in a subset of human breast cancers. Nat Genet 26:291–299

    Article  PubMed  CAS  Google Scholar 

  • Kim JY, Mochizuki T, Akita K, Jung HS (2003) Morphological evidence of the importance of epithelial tissue during mouse tongue development. Exp Cell Res 290:217–226

    Article  PubMed  CAS  Google Scholar 

  • Li H, Corrales CE, Wang Z, Zhao Y, Wang Y, Liu H, Heller S (2005) BMP4 signaling is involved in the generation of inner ear sensory epithelia. BMC Dev Biol 5:16–27

    Article  PubMed  CAS  Google Scholar 

  • Pungchanchaikul P, Gelbier M, Ferretti P, Bloch-Zupan A (2005) Gene expression during palate fusion in vivo and in vitro. J Dent Res 84:526–531

    Article  PubMed  CAS  Google Scholar 

  • Rallis C, Del Buono J, Logan MP (2005) Tbx3 can alter limb position along the rostrocaudal axis of the developing embryo. Development 132:1961–1970

    Article  PubMed  CAS  Google Scholar 

  • Suzuki T, Takeuchi J, Koshiba-Takeuchi K, Ogura T (2004) Tbx genes specify posterior digit identity through Shh and BMP signaling. Dev Cell 6:43–53

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi JK, Koshiba-Takeuchi K, Suzuki T, Kamimura M, Ogura K, Ogura T (2003) Tbx5 and Tbx4 trigger limb initiation through activation of the Wnt/Fgf signaling cascade. Development 130:2729–2739

    Article  PubMed  CAS  Google Scholar 

  • Taya Y, O’Kane S, Ferguson MW (1999) Pathogenesis of cleft palate in TGF-beta3 knockout mice. Development 126:3869–3879

    PubMed  CAS  Google Scholar 

  • Tucker AS, Al Khamis A, Sharpe PT (1998) Interactions between Bmp-4 and Msx-1 act to restrict gene expression to odontogenic mesenchyme. Dev Dyn 212:533–539

    Article  PubMed  CAS  Google Scholar 

  • Tumpel S, Sanz-Ezquerro JJ, Isaac A, Eblaghie MC, Dobson J, Tickle C (2002) Regulation of Tbx3 expression by anteroposterior signalling in vertebrate limb development. Dev Biol 250:251–262

    Article  PubMed  Google Scholar 

  • Winnier G, Blessing M, Labosky PA, Hogan BL (1995) Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 9:2105–2116

    PubMed  CAS  Google Scholar 

  • Yamada M, Revelli JP, Eichele G, Barron M, Schwartz RJ (2000) Expression of chick Tbx-2, Tbx-3, and Tbx-5 genes during early heart development: evidence for BMP2 induction of Tbx2. Dev Biol 228:95–105

    Article  PubMed  CAS  Google Scholar 

  • Yu L, Gu S, Alappat S, Song Y, Yan M, Zhang X, Zhang G, Jiang Y, Zhang Z, Zhang Y, Chen Y (2005) Shox2-deficient mice exhibit a rare type of incomplete clefting of the secondary palate. Development 132:4397–4406

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Song Y, Zhao X, Zhang X, Fermin C, Chen Y (2002) Rescue of cleft palate in Msx1-deficient mice by transgenic Bmp4 reveals a network of BMP and Shh signaling in the regulation of mammalian palatogenesis. Development 129:4135–4146

    PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We are grateful to Dr. Cheryll Tickle for helpful discussions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Han-Sung Jung.

Additional information

This research was supported by the International Cooperation Research Program of the Ministry of Science & Technology (M6-0302-00-0044).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, JM., Kim, JY., Cho, KW. et al. Modulation of cell proliferation during palatogenesis by the interplay between Tbx3 and Bmp4 . Cell Tissue Res 327, 285–292 (2007). https://doi.org/10.1007/s00441-006-0271-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-006-0271-8

Keywords

Navigation