GFR alpha-1, GFR alpha-2, and GFR alpha-3 constitute a family of struc
turally related, glycosyl-phosphatidylinosital-linked, cell surface pr
oteins, two of which, GFR alpha-1 and GFR alpha-2, are components of t
he receptor complex for the neurotrophic factors GDNF and neurturin, r
espectively. By screening an embryonic chicken brain cDNA library with
a GFR alpha-1 probe at low stringency, we isolated cDNAs encoding an
additional member of the GFR alpha family, GFR alpha-4. The nucleotide
sequence predicts a 431-amino-acid secreted protein that is more clos
ely related to GFR alpha-1 and GFR alpha-2 than to GFR alpha-3. GFR al
pha-4 mRNA is expressed in distinctive patterns in the brain and sever
al other organs and tissues of the chicken embryo. Our findings extend
the family of GFR alpha proteins and provide information about the ti
ssues in which GFR alpha-4 may function during development.