Drs. Bhasin and Kernick contributed equally to this work.
Differential regulation of chondrogenic differentiation by the serotonin2B receptor and retinoic acid in the embryonic mouse hindlimb
Article first published online: 22 APR 2004
Copyright © 2004 Wiley-Liss, Inc.
Volume 230, Issue 2, pages 201–209, June 2004
How to Cite
Bhasin, N., Kernick, E., Luo, X., Seidel, H.E., Weiss, E.R. and Lauder, J.M. (2004), Differential regulation of chondrogenic differentiation by the serotonin2B receptor and retinoic acid in the embryonic mouse hindlimb. Dev. Dyn., 230: 201–209. doi: 10.1002/dvdy.20038
- Issue published online: 12 MAY 2004
- Article first published online: 22 APR 2004
- Manuscript Accepted: 29 DEC 2003
- Manuscript Received: 23 DEC 2003
- NIDCR. Grant Number: DE13314
- 5-HT2B receptor;
- limb bud;
- micromass culture;
Retinoic acid (RA) synthesizing and metabolizing enzymes are coordinately expressed with serotonin 2B (5-HT2B) receptors at sites of epithelial–mesenchymal (E-M) interaction in the mouse embryo (Bhasin et al., 1999). The promoter of the 5-HT2B receptor contains potential RA response element (RAREs) as well as an AP-2 site. Because both retinoid and serotonergic signaling have been implicated in the regulation of chondrogenic differentiation, the present study investigated whether these signals may work together to regulate this morphogenetic process in hindlimb bud micromass cultures. Results indicate that 5-HT promotes [35S]sulfate incorporation (chondrogenic differentiation) by activation of 5-HT2B receptors, which use the mitogen activated protein kinase (p42 MAPK) signal transduction pathway, whereas RA dose-dependently inhibits sulfate incorporation and promotes expression of RARβ, which could lead to inhibition of p38 MAPK. No evidence was found to support the possibility that RA negatively regulates expression of 5-HT2B receptors. Taken together, these results suggest that 5-HT and RA may act as opposing signals to regulate chondrogenic differentiation in the developing hindlimb, possibly mediated by different MAPK signal transduction pathways. Developmental Dynamics 230:201–209, 2004. © 2004 Wiley-Liss, Inc.