We have identified a new member of the transforming growth factor-beta 
(TGF-beta) superfamily, growth/differentiation factor-10 (GDF-10), which is 
highly related to bone morphogenetic protein-3 (BMP-3). The nucleotide sequence 
of GDF-10 encodes a predicted protein of 476 amino acids with a molecular weight 
of approximately 52,000. The GDF-10 polypeptide contains a potential signal 
sequence for secretion, a putative RXXR proteolytic processing site, and a 
carboxy-terminal domain with considerable homology to other known members of the 
TGF-beta superfamily. In the mature carboxy-terminal domain GDF-10 is more 
homologous to BMP-3 (83% amino acid sequence identity) than to any other 
previously identified TGF-beta family member. GDF-10 also shows significant 
homology to BMP-3 (approximately 30% amino acid sequence identity) in the pro- 
region of the molecule. Based on these sequence comparisons, GDF-10 and BMP-3 
define a new subgroup within the larger TGF-beta superfamily. By Northern 
analysis, GDF-10 mRNA was detected primarily in murine uterus, adipose tissue, 
and brain and to a lesser extent in liver and spleen. In addition, GDF-10 mRNA 
was present in both neonatal and adult bone samples, with higher levels being 
detected in calvaria than in long bone. These results suggest that GDF10 may 
play multiple roles in regulating cell differentiation events, including those 
involved in skeletal morphogenesis. Gdf10 was mapped to the proximal region of 
mouse chromosome 14 close to a region known to contain a spontaneous recessive 
mutation that is associated with a craniofacial defect.