Extracellular adenosine deamination primes tip organizer development inDictyostelium

Ammonia is a morphogen inDictyosteliumand is known to arise from the catabolism of proteins and RNA. However, we show that extracellular adenosine deamination catalyzed by adenosine deaminase related growth factor (ADGF), is a major source of ammonia and demonstrate a direct role of ammonia in tip organizer development. The tip formed during early development inDictyosteliumis functionally similar to the embryonic organizer of higher vertebrates.adgfmutants fail to establish an organizer and this could be reversed by exposing the mutants to volatile ammonia. Interestingly, bacteria physically separated from theadgf⁻mounds in a partitioned dish also rescues the mound arrest phenotype suggesting a cross kingdom interaction driving development. Both the substrate, adenosine and the product, ammonia regulateadgfexpression, andadgfacts downstream of the histidine kinasedhkDin regulating tip formation. Thus, the consecutive transformation of extracellular cAMP to adenosine, and adenosine to ammonia are integral steps duringDictyosteliumdevelopment. Remarkably, in higher vertebrates,adgfexpression is elevated during gastrulation and thus adenosine deamination may be an evolutionarily conserved process driving organizer development.