Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Follicular cells of the thyroid gland require Pax8 gene function

Abstract

The thyroid gland develops from two distinct embryonic lineages: follicular cells (which produce thyroxine) and parafollicular C-cells (which produce calcitonin) are of endodermal and neural crest origin, respectively. Little is known about the molecular mechanisms governing the generation of these different cell types. Mice lacking the transcription factor Ttf 1 lack both cell types and thus are unable to develop a thyroid gland. By analysis of Pax8−/− mice, we demonstrate that Pax8 is required for the formation of the follicular cells in the thyroid. We present evidence that Pax8 is necessary for providing cues for the differentiation of competent endoderm primordia into thyroxin-producing follicular cells.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kimura, S. et al. The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev. 10, 60–69 (1996).

    Article  CAS  PubMed  Google Scholar 

  2. Manley, N.R. & Capecchi, M.R. The role of Hoxa-3 in mouse thymus and thyroid development. Development 121, 1989–2003 (1995).

    CAS  PubMed  Google Scholar 

  3. Sosa-Pineda, B., Chowdhury, K., Torres, M., Oliver, G. & Gruss, P. The Pax4 gene is essential for the differentiation of insulin-producing β-cells in mammalian pancreas. Nature 386, 399–402 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. St-Onge, L., Sosa-Pineda, B., Chowdhury, K., Mansouri, A. & Gruss, P. Pax6 is required for differentiation of glucagon-producing α-cells in mouse pancreas. Nature 387, 406–409 (1997).

    Article  CAS  PubMed  Google Scholar 

  5. Plachov, D. et al. Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development 110, 643–651 (1990).

    CAS  PubMed  Google Scholar 

  6. Dressler, G.R., Deutsch, U., Chowdhury, K., Nornes, H.O. & Gruss, P. Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development 109, 787–795 (1990).

    CAS  PubMed  Google Scholar 

  7. Asano, M. & Gruss, P. Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development Mech. Dev. 39, 29–39 (1992).

    Article  CAS  PubMed  Google Scholar 

  8. Urbank, P., Wang, Z.Q., Fetka, I, Wagner, E.F. & Busslinger, M. Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax/BSAP. Cell 79, 901–912 (1994).

    Article  Google Scholar 

  9. Hilfer, S.R. Cellular interactions in the genesis and maintenance of thyroid characteristics. in Epithelial-Mesenchymal Interactions (eds Fleischmajer, R. & Billingham, R.E.) 177–199 (Williams and Wilkins Co, Baltimore, 1968).

  10. Pearse, A.G.E. & Carvalheira, A.F. Cytochemical evidence for an Ultimobranchial origin of rodent thyroid C cells. Nature 214, 929–930 (1967).

    Article  CAS  PubMed  Google Scholar 

  11. Le Lievre, C.S. & Le Douarin, N.M. Mesenchymal derivatives of the neural crest: analysis of chimaeric quail and chick embryos. J. Embryol. Exp. Morph. 34, 125–154 (1975).

    CAS  PubMed  Google Scholar 

  12. Fontaine, J. Multistep migration of calcitonin cell precursors during ontogeny of the mouse pharynx. Gen. Comp. Endocrinol. 37, 81–92 (1979).

    Article  CAS  PubMed  Google Scholar 

  13. Lazzaro, D., Price, M., De Felice, M. & Di Lauro, R. The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain. Development 113, 1093–1104 (1991).

    CAS  PubMed  Google Scholar 

  14. Pohl, V. et al. Differentiation expression during proliferative activity induced through different pathways: in situ hybridization study of thyroglobulin gene expression in thyroid epithelial cells. J. Cell Biol. 111, 663–672 (1990).

    Article  CAS  PubMed  Google Scholar 

  15. Macchia, P. et al. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nature Genet. 19, 83–86 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Steel, K.P. & Smith, R.J.H. Normal hearing in Splotch (Sp/+), the mouse homologue of Waardenburg syndrome type 1. Nature Genet. 2, 75–79 (1992).

    Article  CAS  PubMed  Google Scholar 

  17. Torres, M. & Mansouri, A. Gene targeting by homologous recombination in embryonic stem cells. in Cell Biology: A Laboratory Handbook (ed. Celis, J.E.) 112–118 (Academic Press Inc., San Diego, New York, 1994).

    Chapter  Google Scholar 

  18. Nagy, A. & Rossant, J. Production of completely ES cell-derived fetuses. in Gene targeting. A Practical Approach (eds. Joyner, A.L.) 147–178 (IRL press, Oxford, 1993).

    Google Scholar 

  19. Mansour, S.L., Thomas, K.R. & Capecchi, M.R. Disruption of the prot-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature 336, 348–352 (1988).

    Article  CAS  PubMed  Google Scholar 

  20. Wilkinson, D.G. In Situ Hybridisation; a Practical Approach (Oxford University Press, London, 1992).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter Gruss.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mansouri, A., Chowdhury, K. & Gruss, P. Follicular cells of the thyroid gland require Pax8 gene function. Nat Genet 19, 87–90 (1998). https://doi.org/10.1038/ng0598-87

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0598-87

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing