(A) function of Drosophila POU domain motif 3 (Pdm3) regulating wingless (wg) transcription in Neuromuscular junction (NMJ)

Abstract

Wnt is a conserved family of secreted proteins that play diverse roles in tissue growth and differentiation. Identification of transcription factors that regulate $wnt$ expression is pivotal for understanding tissue-specific signaling pathways regulated by Wnt. We identified $pdm3^{m7}$, a new allele of the $pdm3$ gene encoding a POU family transcription factor, in a lethality-based genetic screen for modifiers of Wingless (Wg) signaling in $Drosophila$. Interestingly, $pdm3^{m7}$ larvae showed slow locomotion, implying neuromuscular defects. Analysis of larval neuromuscular junctions (NMJs) revealed decreased bouton number with enlarged bouton in $pdm3$ mutants. $pdm3$ NMJs also had fewer branches at axon terminals than wild-type NMJs. Consistent with $pdm3^{m7}$ being a candidate $wg$ modifier, NMJ phenotypes in $pdm3$ mutants were similar to those of $wg$ mutants, implying a functional link between these two genes. Indeed, lethality caused by Pdm3 overexpression in motor neurons was completely rescued by knockdown of $wg$, indicating that Pdm3 acts upstream to Wg. Furthermore, transient expression of Pdm3 induced ectopic expression of wg-LacZ reporter and Wg effector proteins in wing discs. We propose that Pdm3 expressed in presynaptic NMJ neurons regulates $wg$ transcription for growth and development of both presynaptic neurons and postsynaptic muscles.