QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 30 November 2005
doi: 10.1242/dev.02171

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.02171v1 133/1/63    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deckelbaum, R. A. Articles by Loomis, C. A. Search for Related Content PubMed PubMed Citation Articles by Deckelbaum, R. A. Articles by Loomis, C. A.

The homeoprotein engrailed 1 has pleiotropic functions in calvarial intramembranous bone formation and remodeling

¹ Department of Cell Biology, New York University School of Medicine, MSB room 614, 550 1st Avenue, New York, NY 10016, USA.
² Faculty of Medicine, Centre for Bone and Periodontal Research, McGill University, Room 2203, 740 Avenue Dr Penfield, Montreal, Québec H3A 1A4, Canada.
³ Departments of Pathology and Dermatology, New York University School of Medicine, MSB room 614, 550 1st Avenue, New York, NY 10016, USA.

^* Corresponding author (e-mail: loomic01{at}med.nyu.edu)

Accepted 19 October 2005

The membranous bones of the mammalian skull vault arise from discrete condensations of neural crest- and mesodermally-derived cells. Recently, a number of homeodomain transcription factors have been identified as critical regulators of this process. Here, we show that the homeoprotein engrailed 1 (EN1) is expressed during embryonic and perinatal craniofacial bone development, where it localizes to the skeletogenic mesenchyme, and, subsequently, to calvarial osteoblasts and osteoprogenitors. Mice lacking En1 exhibit generalized calvarial bone hypoplasia and persistent widening of the sutural joints. A reduction in calvarial membranous bone deposition and mineralization (osteopenia) is coupled to enhanced osteolytic resorption in En1 mutants. Consistent with these observations, expression of established osteoblast differentiation markers reveals that En1 function is required for both early and late phases of calvarial osteogenesis. Further analysis shows that EN1 regulates FGF signaling in calvarial osteoblasts. Moreover, EN1 indirectly influences calvarial osteoclast recruitment and bone resorption by regulating the expression of receptor activator of NFB ligand (RANKL) in osteoblasts. Thus, during intramembranous bone formation, EN1 acts both cell autonomously and non-cell autonomously. In summary, this study identifies EN1 as a novel modulator of calvarial osteoblast differentiation and proliferation, processes that must be exquisitely balanced to ensure proper skull vault formation.

Key words: Calvarial bone, En1, Osterix, Osteoblasts, Osteoclasts

This article has been cited by other articles:

				V. Todorovic, D. Frendewey, D. E. Gutstein, Y. Chen, L. Freyer, E. Finnegan, F. Liu, A. Murphy, D. Valenzuela, G. Yancopoulos, et al. Long form of latent TGF-{beta} binding protein 1 (Ltbp1L) is essential for cardiac outflow tract septation and remodeling Development, October 15, 2007; 134(20): 3723 - 3732. [Abstract] [Full Text] [PDF]