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J. Biol. Chem., Vol. 275, Issue 51, 40036-40041, December 22, 2000

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Fdp, a New Fibrocyte-derived Protein Related to MIA/CD-RAP, Has an in Vitro Effect on the Early Differentiation of the Inner Ear Mesenchyme^*

Martine Cohen-Salmon, Dorothy Frenz^§¶, Wei Liu^§, Elizabeth Verpy, Stéphanie Voegeling, and Christine Petit^**

From the  Unité de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France, the Departments of ^§ Otolaryngology and ^¶ Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, and the  Unité de Génétique des Mammifères, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France

During the course of a study aimed at isolating transcripts specifically or preferentially expressed in the inner ear, we identified a novel gene, encoding a fibrocyte-derived protein, that we named Fdp. Fdp is predicted to be a secreted 128-amino acid protein, which is highly homologous to the melanoma-inhibiting activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP), a cartilage-specific protein also expressed in several tumors. Fdp and MIA/CD-RAP thus define a new family of proteins. Fdp is expressed from embryonic day 10.5 in the mesenchyme surrounding the otic epithelium. During development, these cells progressively aggregate, condense, and differentiate into cartilaginous cells forming the otic capsule, which no longer expresses Fdp, and into fibrocytes surrounding the epithelia, which strongly express Fdp. In order to address the function of Fdp, we developed an in vitro antisense oligonucleotide approach using microdissected periotic mesenchyme micromass cultures, and showed that Fdp antisense oligonucleotide treatment results in a significant reduction in chondrogenesis. Our results demonstrate that Fdp plays a role in the initiation of periotic mesenchyme chondrogenesis. Accordingly, Fdp and its human ortholog FDP, which map to chromosome 2 and band 20p11, respectively, could be candidate genes for forms of deafness associated with malformations of the otic capsule.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EMBL Data Bank with accession number(s) AF243504 (Fdp) and AF243505 (FDP).

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