Morphogenic proteins

Abstract

DAN (Differential-screening-selected gene Aberrative in Neuroblastoma) and gremlin proteins and related nucleic acids are provided. Included are natural DAN and gremlin homologs from several species and proteins comprising a DAN or gremlin domain having specific activity, particularly the ability to antagonize a bone morphogenic protein. The proteins may be produced recombinantly from transformed host cells with the subject nucleic acids. Also provided are isolated hybridization probes and primers capable of specifically hybridizing with the disclosed genes, specific binding agents and methods of making and using the subject compositions.

What is claimed is:  
     
         1 . A method for reducing morphogen-dependent bone formation of a cell comprising an extracellular surface in contact with a medium, said method comprising the step of: 
 contacting said medium with an antagonist of a bone morphogenie protein (BMP) selected from the group consisting of human BMP2 and human BMP4, said antagonist produced exogenously from said cell and comprising SEQ ID NO:2, 4, 6, 8 or 9 or a deletion mutant of a sequence selected from the group consisting of SEQ ID NO:2 or 8 wherein said deletion mutant encodes a polypeptide that retains at least 8 contiguous amino acids of said SEQ ID NO:2 or 8 and is sufficient to specifically bind and antagonize said BMP, under conditions whereby said morphogen-dependent bone formation is reduced; and    measuring a resultant reduction of said morphogen-dependent bone formation.    
     
     
         2 . A method for reducing morphogen-dependent bone formation of a cell comprising an extracellular surface in contact with a medium, said method comprising the step of: 
 contacting said medium with an antagonist of a bone morphogenic protein (BMP) selected from the group consisting of human BMP2 and human BMP4, said antagonist produced exogenously from said cell and comprising SEQ ID NO:2, or a deletion mutant of SEQ ID NO:2 wherein said deletion mutant encodes a polypeptide that retains at least 8 contiguous amino acids of SEQ ID NO:2 and is sufficient to specifically bind and antagonize said BMP, under conditions whereby said morphogen-dependent bone formation is reduced; and    measuring a resultant reduction of said morphogen-dependent bone formation.    
     
     
         3 . A method for reducing morphogen-dependent bone formation of a cell comprising an extracellular surface in contact with a medium, said method comprising the step of: 
 contacting said medium with an antagonist of a bone morphogenic protein (BMP) selected from the group consisting of human BMP2 and human BMP4, said antagonist produced exogenously from said cell and comprising SEQ ID NO:8, or a deletion mutant of SEQ ID NO:8 wherein said deletion mutant encodes a polypeptide that retains at least 8 contiguous amino acids of SEQ ID NO:8 and is sufficient to specifically bind and antagonize said BMP, under conditions whereby said morphogen-dependent bone formation is reduced; and    measuring a resultant reduction of said morphogen-dependent bone formation.    
     
     
         4 . A method according to  claim 1 , wherein said cell is in situ and said medium is a physiological fluid comprising said BMP.  
     
     
         5 . A method according to  claim 2 , wherein said cell is in situ and said medium is a physiological fluid comprising said BMP.  
     
     
         6 . A method according to  claim 3 , wherein said cell is in situ and said medium is a physiological fluid comprising said BMP.