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Differential regulation of chondrogenic differentiation by the serotonin 2B receptor and retinoic acid in the embryonic mouse hindlimb
Author(s) -
Bhasin N.,
Kernick E.,
Luo X.,
Seidel H.E.,
Weiss E.R.,
Lauder J.M.
Publication year - 2004
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20038
Subject(s) - retinoic acid , biology , chondrogenesis , limb bud , microbiology and biotechnology , signal transduction , mapk/erk pathway , receptor , serotonergic , serotonin , endocrinology , mesenchymal stem cell , biochemistry , embryo , gene
Retinoic acid (RA) synthesizing and metabolizing enzymes are coordinately expressed with serotonin 2B (5‐HT 2B ) receptors at sites of epithelial–mesenchymal (E‐M) interaction in the mouse embryo (Bhasin et al., 1999). The promoter of the 5‐HT 2B 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 [ 35 S]sulfate incorporation (chondrogenic differentiation) by activation of 5‐HT 2B receptors, which use the mitogen activated protein kinase (p42 MAPK) signal transduction pathway, whereas RA dose‐dependently inhibits sulfate incorporation and promotes expression of RAR β , which could lead to inhibition of p38 MAPK. No evidence was found to support the possibility that RA negatively regulates expression of 5‐HT 2B 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.