[Show abstract][Hide abstract] 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.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 10/2011; 26(10):2463-72. DOI:10.1002/jbmr.458 · 6.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The hair follicle of mammalian skin consists of a group of concentric epithelial cell layers. The inner root sheath (IRS), which surrounds the hardening hair shaft beneath the skin surface, is subdivided into three layers, termed the cuticle of the IRS, Huxley's layer, and Henle's layer. The IRS forms a follicular wall in the hair canal and helps guide the developing hair shaft. c-Maf and MafB, members of the Maf family of transcription factors, play important roles in the developmental processes of various tissues and in cell type-specific gene expression.
The aim of this study is to reveal the pattern of expression and functional roles of c-Maf and MafB in the hair follicle.
We determined the precise location of c-Maf and MafB expression using immunofluorescent staining of mouse skin sections with layer-specific markers. We also analyzed whiskers of c-maf- and mafB-null mice (c-maf(-/-) and mafB(-/-), respectively) using scanning electron microscopy.
c-Maf and MafB were differentially expressed in the Huxley's and Henle's layers of the IRS. Scanning electron microscopic analysis showed irregular cuticle patterning of whiskers of c-maf(-/-) and mafB(-/-) mice. The cuticles of mafB(-/-) mice were also thinner than those of wild-type mice.
c-Maf and MafB are expressed in the IRS layers in a lineage-restricted manner and are involved in hair morphogenesis.