TY - JOUR
T1 - MafB interacts with Gcm2 and regulates parathyroid hormone expression and parathyroid development
AU - Kamitani-Kawamoto, Akiyo
AU - Hamada, Michito
AU - Moriguchi, Takashi
AU - Miyai, Masashi
AU - Saji, Fumie
AU - Hatamura, Ikuji
AU - Nishikawa, Keizo
AU - Takayanagi, Hiroshi
AU - Hitoshi, Seiji
AU - Ikenaka, Kazuhiro
AU - Hosoya, Toshihiko
AU - Hotta, Yoshiki
AU - Takahashi, Satoru
AU - Kataoka, Kohsuke
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - GCM2
KW - MafB
KW - parathyroid gland
KW - parathyroid hormone
KW - transcriptional regulation
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U2 - 10.1002/jbmr.458
DO - 10.1002/jbmr.458
M3 - Article
C2 - 21713993
AN - SCOPUS:80053198680
VL - 26
SP - 2463
EP - 2472
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 10
ER -