English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/146672
logo share SHARE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a new brain-to-bone signaling pathway

AuthorsSuárez-Bregua, Paula ; Torres-Núñez, Eva ; Cerdá-Reverter, José Miguel ; Rotllant, Josep
Issue Date2017
PublisherFederation of American Societies for Experimental Biology
CitationFASEB Journal - Federation of American Societies for Experimental Biology 31(2): 569-583 (2017)
AbstractRegulation of bone development, growth, and remodeling traditionally has been thought to depend on endocrine and autocrine/paracrine modulators. Recently, however, brain-derived signals have emerged as key regulators of bone metabolism, although their mechanisms of action have been poorly understood. We reveal the existence of an ancient parathyroid hormone (Pth)4 in zebrafish that was secondarily lost in the eutherian mammals’ lineage, including humans, and that is specifically expressed in neurons of the hypothalamus and appears to be a central neural regulator of bone development and mineral homeostasis. Transgenic fish lines enabled mapping of axonal projections leading from the hypothalamus to the brainstem and spinal cord. Targeted laser ablation demonstrated an essential role for of pth4-expressing neurons in larval bone mineralization. Moreover, we show that Runx2 is a direct regulator of pth4 expression and that Pth4 can activate cAMP signaling mediated by Pth receptors. Finally, gain-of-function experiments show that Pth4 can alter calcium/phosphorus levels and affect expression of genes involved in phosphate homeostasis. Based on our discovery and characterization of Pth4, we propose a model for evolution of bone homeostasis in the context of the vertebrate transition from an aquatic to a terrestrial lifestyle
Description15 páginas, 9 figuras.-- Paula Suárez-Bregua et al.
Publisher version (URL)http://dx.doi.org/10.1096/fj.201600815R
Appears in Collections:(IIM) Artículos
(IATS) Artículos
Files in This Item:
File Description SizeFormat 
PTH4_ancient_parathyroid_2017.pdf10,28 MBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.