The Drosophila Pahnitoyl Protein Thioesterase 1, A Homologue Of The Batten Disease Ppt1 Gene, Is Required For Normal Embryonic Neural Development

The Drosophila Palmitoyl Protein Thioesterase 1 (Ppt1) gene was previously identified to be a homolog of the human PPT1 gene. Defects in human PPT1 leads to the pediatric neurological disease called Infantile Neuronal Ceroids Lipofuscinosis (INCL). It is known that removal of the fly Ppt1 protein results in neural phenotype reminiscent of the human disease, the accumulation of autofluorescence deposits and decreased lifespan in adults. Since INCL patients die at a young age, earlier developmental neural defects due to the loss of PPT1 are postulated but have yet to be elucidated. Our results indicate that Drosophila Ppt1 may provide insights into how the loss of Ppt1 function results in developmental neural defects. In the absence of Ppt1, the earliest neural phenotype is detected as early as stage 11 embryogenesis with altered expression in an identified motoneuron lineage, the RP2 motoneuron. Ppt1 mutant embryos exhibit partial loss of even-skipped expressing GMC4.2a and later, RP2 neuron, in addition to a decreased in the number of EL neurons. Neural defects are not restricted to just this motoneuron: Ppt1 mutants also display abnormal CNS and PNS development as detected by BP102 and 22C10 immunohistochemistry. We are currently investigating whether these axonal defects are due to the death of the RP2 motoneuron as well as to neurons in other identified neuronal lineages.