MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development

Akiyo Kamitani-Kawamoto, Michito Hamada, Takashi Moriguchi, Masashi Miyai, Fumie Saji, Ikuji Hatamura, Keizo Nishikawa, Hiroshi Takayanagi, Seiji Hitoshi, Kazuhiro Ikenaka, Toshihiko Hosoya, Yoshiki Hotta, Satoru Takahashi, Kohsuke Kataoka

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Serum calcium and phosphate homeostasis is critically regulated by parathyroid hormone (PTH) secreted by the parathyroid glands. Parathyroid glands develop from the bilateral parathyroid-thymus common primordia. In mice, the expression of transcription factor Glial cell missing 2 (Gcm2) begins in the dorsal/anterior part of the primordium on embryonic day 9.5 (E9.5), specifying the parathyroid domain. The parathyroid primordium then separates from the thymus primordium and migrates to its adult location beside the thyroid gland by E15.5. Genetic ablation of gcm2 results in parathyroid agenesis in mice, indicating that Gcm2 is essential for early parathyroid organogenesis. However, the regulation of parathyroid development at later stages is not well understood. Here we show that transcriptional activator v-maf musculoaponeurotic fibrosarcoma oncogene homologue B (MafB) is developmentally expressed in parathyroid cells after E11.5. MafB expression was lost in the parathyroid primordium of gcm2 null mice. The parathyroid glands of mafB +/- mice were mislocalized between the thymus and thyroid. In mafB -/- mice, the parathyroid did not separate from the thymus. Furthermore, in mafB -/- mice, PTH expression and secretion were impaired; expression levels of renal cyp27b1, one of the target genes of PTH, was decreased; and bone mineralization was reduced. We also demonstrate that although Gcm2 alone does not stimulate the PTH gene promoter, it associates with MafB to synergistically activate PTH expression. Taken together, our results suggest that MafB regulates later steps of parathyroid development, that is, separation from the thymus and migration toward the thyroid. MafB also regulates the expression of PTH in cooperation with Gcm2.

Original languageEnglish
Pages (from-to)2463-2472
Number of pages10
JournalJournal of Bone and Mineral Research
Volume26
Issue number10
DOIs
Publication statusPublished - 2011 Oct 1

Keywords

  • GCM2
  • MafB
  • parathyroid gland
  • parathyroid hormone
  • transcriptional regulation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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  • Cite this

    Kamitani-Kawamoto, A., Hamada, M., Moriguchi, T., Miyai, M., Saji, F., Hatamura, I., Nishikawa, K., Takayanagi, H., Hitoshi, S., Ikenaka, K., Hosoya, T., Hotta, Y., Takahashi, S., & Kataoka, K. (2011). MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development. Journal of Bone and Mineral Research, 26(10), 2463-2472. https://doi.org/10.1002/jbmr.458