The Drosophila Par Domain Protein I Gene, Pdp1, is a Regulator of Larval Growth, Mitosis and Endoreplication

PDP1 is a basic leucine zipper (bZip) transcription factor that is expressed at high levels in the muscle, epidermis, gut and fat body of the developing Drosophila embryo. We have identified three mutant alleles of Pdp1, each having a similar phenotype. Here, we describe in detail the Pdp1 mutant allele, Pdp1(p205), which is null for both Pdp1 RNA and protein. Interestingly, homozygous Pdp1(p205) embryos develop normally, hatch and become viable larvae. Analyses of Pdp1 null mutant embryos reveal that the overall muscle pattern is normal as is the patterning of the gut and fat body. Pdp1(p205) larvae also appear to have normal muscle and gut function and respond to ecdysone. These larvae, however, are severely growth delayed and arrested. Furthermore, although Pdp1 null larvae live a normal life span, they do not form pupae and thus do not give rise to eclosed flies. The stunted growth of Pdp1(p205) larvae is accompanied by defects in mitosis and endoreplication similar to that associated with nutritional deprivation. The cellular defects resulting from the Pdp1(p205) mutation are not cell autonomous. Moreover, PDP1 expression is sensitive to nutritional conditions, suggesting a link between nutrition, PDP1 isotype expression and growth. These results indicate that Pdp1 has a critical role in coordinating growth and DNA replication.