A GENETIC SCREEN FOR MODIFIERS OF DROSOPHILA DECAPENTAPLEGIC SIGNALING IDENTIFIES MUTATIONS IN PUNT, MOTHERS AGAINST DPP AND THE BMP-7 HOMOLOG, 60A

decapentaplegic (dpp) is a Transforming Growth Factor beta (TGF-beta)- related growth factor that controls multiple developmental processes i n Drosophila, To identify components involved in dpp signaling, we car ried out a genetic screen for dominant enhancer mutations of a hypomor phic allele of thick veins (tkv), a type I receptor for dpp, We recove red new alleles of tkv, pant, Mothers against dpp (Mad) and Medea (Med ), all of which are known to mediate dpp signaling. We also recovered mutations in the 60A gene which encodes another TGF-beta-related facto r in Drosophila. DNA sequence analysis established that all three 60A alleles were nonsense mutations in the prodomain of the 60A polypeptid e. These mutations in 60A caused defects in midgut morphogenesis and f at body differentiation. We present evidence that when dpp signaling i s compromised, lowering the level of 60A impairs several dpp-dependent developmental processes examined, including the patterning of the vis ceral mesoderm, the embryonic ectoderm and the imaginal discs. These r esults provide the first in vivo evidence for the involvement of 60A i n the dpp pathway. We propose that 60A activity is required to maintai n optimal signaling capacity of the dpp pathway, possibly by forming b iologically active heterodimers with Dpp proteins.