The regulatory effects of signaling proteins like hormones, growth factors, and cytokines are mediated by specific cell surface receptors which are grouped into distinct families on the basis of structural criteria. Here we report on the isolation and embryonic expression of a novel mouse gene, Etl2 (enhancer trap locus 2) which, based on its deduced amino acid sequence, constitutes a new member of the cytokine type-I receptor family. Among type-I receptors Etl2 is most similar to the alpha subunits of the human ciliary neurotrophic factor (CNTF) receptor and the mouse interleukin-6 (IL6) receptor with 32 and 30% identical amino acids, respectively. From Day 9 p.c. (postcoitum) onward low levels of Etl2 mRNA were detected in mesenchymal cells throughout the embryo and in parts of the nervous system, in particular in the ependymal linings of the spinal cord and the developing brain vesicles and in the neuronal layer of the retina. Highest levels of Etl2 expression were found on Day 12.5 p.c. in the craniofacial mesenchyme and during subsequent development in mesenchymal cells around all developing cartilages. At later stages, Etl2 transcripts were abundant in the dental papilla, the dermis, and hair follicles, as well as in the perichondrium and periost, i.e., in regions containing chondro and osteo progenitor cells. Etl2 mRNA was not detected, however, in mature odontoblasts, chondroblasts, osteoblasts, chondrocytes, and osteocytes. Our results suggest that Etl2 is a new orphan receptor belonging to the type-I cytokine receptor family and that Etl2 might have regulatory functions, particularly in the control of proliferation and/or differentiation of skeletogenic progenitor and other mesenchymal cells.