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Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme.
Dev Biol 2007; 304(2):860-74DB

Abstract

Craniofacial bones derive from cephalic neural crest, by endochondral or intramembranous ossification. Here, we address the role of the homeobox transcription factor Dlx5 during the initial steps of calvaria membranous differentiation and we show that Dlx5 elicits Runx2 induction and full osteoblast differentiation in embryonic suture mesenchyme grown "in vitro". First, we compare Dlx5 expression to bone-related gene expression in the developing skull and mandibular bones. We classify genes into three groups related to consecutive steps of ossification. Secondly, we study Dlx5 activity in osteoblast precursors, by transfecting Dlx5 into skull mesenchyme dissected prior to the onset of either Dlx5 and Runx2 expression or osteogenesis. We find that Dlx5 does not modify the proliferation rate or the expression of suture markers in the immature calvaria cells. Rather, Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis "in vivo". Thirdly, we show that BMP signaling activates Dlx5, Runx2, and alkaline phosphatase in those primary cultures and that a dominant-negative Dlx factor interferes with the ability of the BMP pathway to activate Runx2 expression. Together, these data suggest a pivotal role of Dlx5 and related Dlx factors in the onset of differentiation of chick calvaria osteoblasts.

Authors+Show Affiliations

CNRS UMR 7128, Institut d'Embryologie Cellulaire et Moléculaire, 94736 Nogent-sur-Marne, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17335796

Citation

Holleville, Nicolas, et al. "Dlx5 Drives Runx2 Expression and Osteogenic Differentiation in Developing Cranial Suture Mesenchyme." Developmental Biology, vol. 304, no. 2, 2007, pp. 860-74.
Holleville N, Matéos S, Bontoux M, et al. Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. Dev Biol. 2007;304(2):860-74.
Holleville, N., Matéos, S., Bontoux, M., Bollerot, K., & Monsoro-Burq, A. H. (2007). Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. Developmental Biology, 304(2), pp. 860-74.
Holleville N, et al. Dlx5 Drives Runx2 Expression and Osteogenic Differentiation in Developing Cranial Suture Mesenchyme. Dev Biol. 2007 Apr 15;304(2):860-74. PubMed PMID: 17335796.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture mesenchyme. AU - Holleville,Nicolas, AU - Matéos,Stéphanie, AU - Bontoux,Martine, AU - Bollerot,Karine, AU - Monsoro-Burq,Anne-Hélène, Y1 - 2007/01/09/ PY - 2006/07/26/received PY - 2006/12/07/revised PY - 2007/01/04/accepted PY - 2007/3/6/pubmed PY - 2007/7/13/medline PY - 2007/3/6/entrez SP - 860 EP - 74 JF - Developmental biology JO - Dev. Biol. VL - 304 IS - 2 N2 - Craniofacial bones derive from cephalic neural crest, by endochondral or intramembranous ossification. Here, we address the role of the homeobox transcription factor Dlx5 during the initial steps of calvaria membranous differentiation and we show that Dlx5 elicits Runx2 induction and full osteoblast differentiation in embryonic suture mesenchyme grown "in vitro". First, we compare Dlx5 expression to bone-related gene expression in the developing skull and mandibular bones. We classify genes into three groups related to consecutive steps of ossification. Secondly, we study Dlx5 activity in osteoblast precursors, by transfecting Dlx5 into skull mesenchyme dissected prior to the onset of either Dlx5 and Runx2 expression or osteogenesis. We find that Dlx5 does not modify the proliferation rate or the expression of suture markers in the immature calvaria cells. Rather, Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis "in vivo". Thirdly, we show that BMP signaling activates Dlx5, Runx2, and alkaline phosphatase in those primary cultures and that a dominant-negative Dlx factor interferes with the ability of the BMP pathway to activate Runx2 expression. Together, these data suggest a pivotal role of Dlx5 and related Dlx factors in the onset of differentiation of chick calvaria osteoblasts. SN - 0012-1606 UR - https://www.unboundmedicine.com/medline/citation/17335796/Dlx5_drives_Runx2_expression_and_osteogenic_differentiation_in_developing_cranial_suture_mesenchyme_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-1606(07)00017-6 DB - PRIME DP - Unbound Medicine ER -