Transcription factors that determine parathyroid development power PTH expression  Tally Naveh-Many, Justin Silver  Kidney International  Volume 93, Issue 1, Pages 7-9 (January 2018) DOI: 10.1016/j.kint.2017.08.026 Copyright © 2017 International Society of Nephrology Terms and Conditions

Figure 1 Parathyroid embryonic development and the regulators of PTH expression and parathyroid cell proliferation. (a) Diagram of the third and fourth pharyngeal pouches showing the embryonic location of the parathyroid and thymus-fated domains in humans and the postnatal position of the parathyroids adjacent to the thyroid glands. (b) Schematic presentations of a parathyroid cell and daughter cells. The different regulators of PTH gene expression, secretion, and parathyroid cell proliferation are shown. Calcium, 1,25D, the high phosphate of uremia, and FGF23 all regulate PTH secretion and PTH gene expression through transcriptional and posttranscriptional mechanisms. In prolonged hypocalcemia and uremia, there is also parathyroid cell proliferation as shown by the 2 small cells on the right. miRNAs are essential for the activation of the parathyroid in secondary hyperparathyroidism. Among the factors affecting parathyroid organogenesis, GATA3, Gcm2, and MafB are all essential for normal gland development and physically interact to activate the PTH gene promoter postnatally. MafB contributes to the increased PTH and cyclin D2 expression in secondary hyperparathyroidism. 1,25(OH)2D3, 1,25-dihydroxyvitamin D3; CaR, calcium-sensing receptor; CKD, chronic kidney disease; FGF23, fibroblast growth factor 23; FGFR, fibroblast growth factor receptor; mRNAs, microRNAs; PTH, parathyroid hormone; 5′-UTR, 5′ untranslated region. Modified from Naveh-Many T. Minireview: the play of proteins on the parathyroid hormone messenger ribonucleic acid regulates its expression. Endocrinology. 2010;151(4):1398–1402, by permission of Oxford University Press. Kidney International 2018 93, 7-9DOI: (10.1016/j.kint.2017.08.026) Copyright © 2017 International Society of Nephrology Terms and Conditions