An Isoform-Specific Mutant Reveals a Role of PDP1ε in the Circadian Oscillator

• DOI: 10.1523/jneurosci.2133-09.2009
• Publication Date: 2009-09-02T17:34:52Z
• Authors: Xiangzhong Zheng; Kyunghee Koh; Mallory Sowcik; Corinne J. Smith; Dechun Chen; Mark N. Wu; Amita Sehgal
• Keywords: Timeless

The Drosophila PAR domain protein 1 ( Pdp1 ) gene encodes a transcription factor with multiple functions. One isoform, PDP1ε, was proposed to be an essential activator of the core clock gene, Clock Clk ). However, central function for PDP1ε recently disputed, and genetic analysis has been difficult due developmental lethality -null mutants. Here we report discovery mutation that specifically disrupts ε isoform. Homozygous mutants are viable exhibit arrhythmic circadian behavior in constant darkness also presence light:dark cycles. Importantly, show diminished expression CLK PERIOD (PER) cells. In addition, PDF (pigment-dispersing factor) is reduced subset Loss alters phosphorylation status cyclic per -luciferase reporter peripheral clocks under free-running conditions. Transgenic neurons can restore rhythmic behavior. transgenic these rescues PER clock, but fails behavioral rhythms, suggesting effects outside molecular clock. Together, data support model which functions oscillator as well output pathway.