Core Feedback Loop Function:

  1. Hardin, P.E., J.C. Hall and M. Rosbash (1990) Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature 343, 536-540.
  2. Zwiebel, L.J., P.E. Hardin, J.C. Hall and M. Rosbash (1991) A post-transcriptional  mechanism contributes to circadian cycling of a per-ß-galactosidase fusion protein. Proc. Natl. Acad. Sci. USA  88, 3882-3886.
  3. Zwiebel, L.J., P.E. Hardin, J.C. Hall and M. Rosbash (1991) Circadian oscillations in the protein and mRNA levels of the periodgene of Drosophila melanogasterBiochem. Soc. Trans. 19, 533-537.
  4. Hardin, P.E., J.C. Hall and M. Rosbash  (1992) Behavioral and molecular analyses suggest that circadian output is disrupted by disconnected mutants in D. melanogasterEMBO J. 11, 1-6.
  5. Hardin, P.E., J.C. Hall and M. Rosbash  (1992) Circadian oscillations of period gene mRNA levels are transcriptionally regulated. Proc. Natl. Acad. Sci. USA 89, 11711-11715.
  6. Hardin, P.E., J.C. Hall and M. Rosbash (1992) Circadian oscillations in the protein and mRNA levels of the period gene of Drosophila melanogaster. In Molecular Genetics of Biological Rhythms (M.W. Young, ed.) Marcel Dekker, New York. pp. 155-169.
  7. Frisch, B., P.E. Hardin, M.J. Hamblen-Coyle, J.C. Hall and M. Rosbash (1994) A promoterless DNA fragment from the periodlocus permits behavioral rhythmicity and mediates cyclical expression of this clock gene in a subset of the Drosophilanervous system. Neuron 12, 555-570.
  8. Zeng, H., P.E. Hardin and M. Rosbash (1994) Constitutive overexpression of the Drosophila period protein inhibits periodmRNA cycling. EMBO J. 13, 3590-3598.
  9. Hardin, P.E. (1994) The molecular genetics of biological rhythms. In Encyclopedia of Time  (S.L Macey, ed.) Garland Publishing, New York. pp. 400-401.
  10. Qiu, J., and P.E. Hardin (1995) Temporal and spatial expression of an adult cuticle protein gene from Drosophila suggests that its protein product may impart some specialized cuticle function.  Dev. Biol. 167, 416-425.
  11. Qiu, J., and P.E. Hardin (1996) Developmental state and the circadian clock interact to influence the timing of eclosion in Drosophila melanogasterJ. Biol. Rhythms 11, 75-86.
  12. Qiu, J., and P.E. Hardin (1996) per mRNA cycling is locked to lights-off under photoperiodic conditions that support circadian feedback loop function. Mol. Cell. Biol. 16, 4182-4188.
  13. Hao, H., D.L. Allen and P.E. Hardin (1997) A circadian enhancer mediates PER-dependent mRNA cycling in DrosophilaMol. Cell. Biol. 17, 3687-3693.
  14. Cheng, Y. and P.E. Hardin (1998) Drosophila photoreceptors contain an autonomous circadian oscillator that can function without period mRNA cycling. J. Neurosci18, 741-750.
  15. Cheng, Y., B. Gvakharia and P.E. Hardin (1998) Two alternatively spliced transcripts from the Drosophila period gene rescue rhythms having different molecular and behavioral characteristics. Mol. Cell. Biol. 18, 6505-6514.
  16. Hardin, P. E. and A. Sehgal (1998) Molecular Components of a Model Circadian Clock: Lessons from Drosophila. In Handbook of Behavioral State Control: Molecular and Physiological Mechanisms (R. Lydic and H. Baghdoyan, eds.) CRC Press, Boca Raton, FL. pp. 61-74.
  17. Hardin, P. E. (1998) Activating inhibitors and inhibiting activators: A day in the life of a fly. Curr. Opin. Neurosci., 8, 642-647.
  18. Hao, H., N.R.J. Glossop, L.C. Lyons, J. Qiu, B. Morrish, Y. Cheng and P.E. Hardin (1999) The period gene circadian regulatory sequence (CRS) mediates correct spatial regulation and behavioral rescue in DrosophilaJ. Neurosci19, 987-994.
  19. Majercak, J., D. Sidote, P.E. Hardin and I. Edery (1999) How a circadian clock adapts to seasonal decreases in temperature and day-length. Neuron 24, 219-230.
  20. Bae, K., C. Lee, P.E. Hardin and I. Edery (2000) dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex. J. Neurosci., 20,1746-1753.
  21. Kaneko, M., J.H. Park, Y. Cheng, P.E. Hardin and J.C. Hall (2000) Disruption of synaptic transmission or clock-gene-product oscillations in circadian pacemaker cells of Drosophila cause abnormal behavioral rhythms. J. Neurobiol43, 207-233.
  22. Lyons, L.C., T.K. Darlington, S.A. Kay and P.E. Hardin (2000) Specific sequences outside of the E-box are required for proper per expression and behavioral rescue. J. Biol. Rhythms 15, 472-482.
  23. Darlington, T.K, L.C. Lyons, P.E. Hardin and S.A. Kay (2000) The period E-box is sufficient to Drive Circadian Transcription in vivoJ. Biol. Rhythms 15, 462-471.
  24. Hardin, P.E. (2000) From biological clock to biological rhythms. Genome Biology 1, 1023.1-1023.5.
  25. Posey, K.L., L.B. Jones, R. Cerda, M. Bajaj, T. Huynh, P.E. Hardin and S.H. Hardin (2001) Survey of transcripts in the adult Drosophila Brain. Genome Biology 2, 0008.1-0008.16.
  26. Blanchardon, E., B. Grima, A. Klarsfeld, E. Chelot, P. E. Hardin, T. Préat and F. Rouyer (2001) Defining the role of Drosophilalateral neurons in the control of activity and eclosion circadian rhythms by targeted genetic ablation and PERIOD protein overexpression. Eur. J. Neurosci. 13, 871-888.
  27. Kim, E.-Y., K. Bae, F. S. Ng, N. R. J. Glossop, P .E Hardin and I. Edery (2002) Drosophila CLOCK is under post-transcriptional control and influences light-induced activity. Neuron34, 69-81.
  28. Hardin, P.E. (2003) Central and peripheral oscillator mechanisms in flies. Cell Technology 22, 1315-1319.
  29. Hardin, P. E. (2004) Transcription regulation within the circadian clock: The E-box and beyond. J. Biol. Rhythms 19, 348-360.
  30. Hardin, P.E. (2005) The circadian system of Drosophila. In Working in the 24 hour Environment (K. Honma and S. Honma, eds.) Hokkaido University Press, Sapporo, pp. 3-16.
  31. Bell-Pedersen, D., V. M. Cassone, D. J. Earnest, S. S. Golden, P. E. Hardin, T. L. Thomas and M. J. Zoran (2005) Multiple oscillators regulate rhythmicity in organisms from bacteria to man. Nat. Rev. Genet. 6, 544-56.
  32. Hardin, P. E. (2005) The Circadian Timekeeping System of DrosophilaCurr. Biol. 15, R714-R722.
  33. Houl, J. H., W. Yu, S. M. Dudek and P. E. Hardin (2006) Drosophila CLOCK accumulates in nuclei of circadian oscillator cells and additional non-oscillator cells at all times of the daily cycle. J. Biol. Rhythms 21, 93-103.
  34. Yu, W., H. Zheng, J. H. Houl and P. E. Hardin (2006) PER dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription. Genes Dev. 20, 723-733.
  35. Yu, W., and P. E. Hardin (2006) Circadian Timekeeping Mechanisms in Animals. J. Cell Sci. 119, 4793-4795.
  36. Hardin, P. E. (2006) Essential and expendable features of the circadian timekeeping mechanism. Curr. Opin. in Neurobiol.16, 686-692.
  37. Kim, E. Y., H. W, Ko, W. Yu, P. E. Hardin and I. Edery (2007) A DOUBLETIME kinase binding domain on the Drosophila PERIOD protein is essential for its hyperphosphorylation, transcriptional repression and circadian clock function. Mol. Cell. Biol. 27, 5014-5028.
  38. Taylor, P., and P. E. Hardin (2008) Rhythmic E-box binding by CLK-CYC controls daily cycles in per and tim transcription and chromatin modifications. Mol. Cell. Biol. 28, 4642-4652.
  39. Hardin, P. E. (2009) Molecular Mechanisms of circadian timekeeping in DrosophilaSleep Biol. Rhythms 7, 235-242.
  40. Yu, W., H. Zheng, J. L. Price and P. E. Hardin (2009) DOUBLETIME functions to bridge CLK phosphorylation by other kinases. Mol. Cell. Biol29, 1452-1458.
  41. Yu, W., J. H. Houl and P. E. Hardin (2011) NEMO kinase contributes to core period determination by slowing the pace of the Drosophila circadian oscillator. Curr. Biol. 21, 756-761.
  42. Hardin. P. E. (2011) Molecular genetic analysis of circadian timekeeping in Drosophila. Adv. Genetics 74, 141-173.
  43. Mahesh, G., E. H. Jeong, F. S. Ng, Y. Liu, K. Gunawardhana, J. H. Houl, E. Yildirim, R. Amunugama, R. Jones, D. L. Allen, I. Edery, E. Y. Kim and P. E. Hardin (2014) Phosphorylation of the transcription activator CLOCK regulates progression through a ~24h feedback loop to influence circadian period in Drosophila. J. Biol. Chem289, 19681-93.
  44. Lee, E., E. H. Jeong, H. J. Jeong, E. Yildirim, J. T. Vanselow, F. S. Ng, Y. Liu, G. Mahesh, A. Kramer, P. E. Hardin, I. Edery and E. Y. Kim (2014) Phosphorylation of a central clock transcription factor is required for thermal but not photic entrainment. PLOS Genetics 10, e1004545.
  45. Zhou, J., W. Yu and P. E. Hardin (2016) CLOCKWORK ORANGE enhances PERIOD mediated rhythms in transcriptional repression by antagonizing E-box binding by CLOCK-CYCLE. PLoS Genet. 12, e1006430.
  46. Agrawal, P. and P. E. Hardin (2016) An RNAi screen to identify protein phosphatases that function within the Drosophilacircadian clock. G3 (Bethesda), 6:4227-4238.
  47. Zhang Y., M. J. Markert, S. C. Groves, P. E. Hardin1 and C. Merlin (2017) Insect vertebrate-like CRYPTOCHROME2 regulates circadian transcription through additive mechanisms on CLOCK and BMAL1. PNAS, in press.

Interlocked Feedback Loops:

  1. Glossop, N.R.J., L.C. Lyons and P.E. Hardin (1999) Interlocked feedback loops within the Drosophila circadian oscillator. Science 286, 766-768.
  2. Hardin, P.E, N.R.J. Glossop, L.C. Lyons, B. Krishnan and S.E. Dryer (2001) The Drosophila circadian oscillator: Molecular circuits and rhythmic outputs. In Zeitgebers, Entrainment and Masking of the Circadian System (K. Honma and S. Honma, eds.) Hokkaido University Press, Sapporo, pp. 77-88.
  3. Glossop, N.R.J. and P.E. Hardin (2002) Central and peripheral circadian oscillator mechanisms in flies and mammals. J. Cell Science 115, 3369-3377.
  4. Glossop, N. R. J.,  J. H. Houl, H. Zheng, F. S. Ng, S. M. Dudek and P. E. Hardin (2003) VRI feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator. Neuron 37, 249-261.
  5. Cyran, S.A., A.M. Buchsbaum, K.L. Reddy, M.-C. Lin, N.R.J. Glossop, P.E. Hardin, M.W. Young, R.V. Storti and J. Blau (2003) vrillePdp1 and dClock form a second feedback loop in the Drosophila circadian clock. Cell 112, 329-341.
  6. Hardin, P.E, B. Krishnan, J.H. Houl, H. Zheng, F.S. Ng, S.E. Dryer and N.R.J. Glossop (2003) Central and peripheral circadian oscillators in DrosophilaNovartis Found. Symp. 253, 140-150.
  7. Smolen, P., B. S. Lo, P. E. Hardin, D. A. Baxter and J. H. Byrne (2004) A Drosophila Circadian Model Incorporating VRI, PDP-1, and CLK Simulates Mutations and Temperature Compensation. Biophys. J. 86, 2786-2802.
  8. Benito, J., H. Zheng and P. E. Hardin (2007) PDP1

     functions downstream of the circadian oscillator to mediate behavioral rhythms. J. Neurosci. 27, 2539-2547.

  9. Matsumoto, A., M. Ukai-Tadenuma, R. G. Yamada, J. Houl, K. D. Uno, T. Kasukawa, B. Dauwalder, T. Q. Ito, K. Takahashi, R. Ueda, P. E. Hardin, T. Tanimura and H. R. Ueda (2007) A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes Dev. 21, 1687-1700.
  10. Benito, J., H. Zheng, F. S. Ng and P. E. Hardin (2007) Transcriptional feedback loop regulation, function and ontogeny in DrosophilaCold Spring Harbor Sym. Quant. Biol.72, 437-444.
  11. Zheng, H., F. S. Ng, Y. Liu and P. E. Hardin (2008) Spatial and Circadian Regulation of cry in DrosophilaJ. Biol. Rhythms 23, 283-295.
  12. Benito, J., J. H. Houl, G. W. Roman and P. E. Hardin (2008) The Blue Light Photoreceptor CRYPTOCHROME is Expressed in a Subset of Circadian Oscillator Neurons in the Drosophila CNS. J. Biol. Rhythms 23, 296-307.
  13. Benito, J., V. Hoxha, C. Lama, A. Lazareva, J-F. Ferveur, P. E. Hardin and B. Dauwalder (2010) The circadian output gene takeout is regulated by Pdp1. Proc. Natl. Acad. Sci. USA 107, 2544-2549.
  14. Gunawardhana K. and P. E. Hardin (2017) VRILLE controls PDF neuropeptide accumulation and arborization rhythms in small ventrolateral neurons to drive rhythmic behavior in Drosophila. Submitted.

Clock Cell Development/Clock Gene Spatial Regulation:

  1. Hardin, P.E. (1994) Analysis of period mRNA cycling in Drosophila head and body tissues indicates that body oscillators behave differently from head oscillators. Mol. Cell. Biol. 4, 7211-7218.
  2. Yu, W., and P. E. Hardin (2007) Use of firefly luciferase assays to monitor circadian molecular rhythms in vivo. In Methods in Molecular Biology (E. Rosato, ed.) Humana Press, Inc., New Jersey, vol. 362, 465-480.
  3. Houl, J. H., F. Ng, P. Taylor and P. E. Hardin (2008) CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos. BMC Neurosci9, 119.
  4. Zhang, Y., Y. Liu, D. Wentworth, P. E. Hardin and P. Emery (2010) Light and temperature control the contribution of a subset of Dorsal Neurons 1 to Drosophila circadian behavior. Curr. Biol. 20, 591-599.
  5. Zhang, L., B. Y. Chung, B. C. Lear, V. L. Kilman, Y. Liu, G. Mahesh, R. Meissner, P. E. Hardin and R. Allada (2010) A sunset of circadian neurons coordinates light and PDF signaling to produce robust daily behavior in DrosophilaCurr. Biol.  20, 600-605.
  6. Kaneko, H., L. M. Head, J. Ling, Y. Liu, P. E. Hardin, P. Emery, F. N. Hamada (2012) Circadian rhythm of temperature preference and its neural control in Drosophila. Submitted.
  7. Glossop, N. R. J., I. Ghangrekar, G. A. Coutts, P. E. Hardin, J. O. Gummadova (2014) TWIN-OF-EYELESS (TOY) functions directly upstream of Clock to initiate and maintain circadian fate in central pacemaker cells that coordinate sleep-wake cycles. J. Biol. Rhythms 29, 151-166.
  8. Liu, T., G. Mahesh, J. H. Houl and P. E. Hardin (2015) Circadian activators are expressed days before they initiate clock function in late pacemaker neurons from Drosophila. J. Neurosci. 35, 8662-8671.
  9. Agrawal, P. and P. E. Hardin (2016) The Drosophila receptor protein tyrosine phosphatase LAR is required for development of circadian pacemaker neuron processes that support rhythmic activity in constant darkness but is not required for activity rhythms during light:dark cycles. J. Neurosci. 36, 3860-3870.
  10. Liu T., G. Mahesh, W. Yu, and P. E. Hardin (2017) CLOCK stabilizes CYCLE to initiate clock function in Drosophila. Submitted.

Physiological and Behavioral Rhythms:

  1. Krishnan, B., S.E. Dryer and P.E. Hardin (1999) Circadian rhythms in olfactory responses of Drosophila melanogasterNature 400, 375-378.
  2. Dryer, S. E., B. Krishnan and P. E. Hardin (1999) Circadian clocks regulate olfactory responses.  ChemoSense 1, 1-3.
  3. Krishnan, B., J. D. Levine, K. Sisson, H. B. Dowse, P. Funes, J. C. Hall, P. E. Hardin and S. E. Dryer (2001) A novel role for cryptochrome in a Drosophila circadian oscillator. Nature 411, 313-317.
  4. Tanoue, S., P. Krishnan, B. Krishnan, S.E. Dryer and P.E. Hardin (2004) Circadian clocks in antennal neurons are required for olfaction rhythms in DrosophilaCurr. Biol. 14, 638-649.
  5. Ge, H., P. Krishnan, L. Liu, B. Krishnan, R. L. Davis, P. E. Hardin and G. W. Roman (2005) A Drosophila non-visual arrestin is required for the maintenance of olfactory sensitivity. Chemical Senses 31, 49-62.
  6. Krishnan, P., S. E. Dryer and P. E. Hardin (2005) Measuring circadian rhythms in olfaction using electroantennograms. Meth. Enz. 393, 495-508.
  7. Fujii, S., P. Krishnan, P. E. Hardin and H. Amrein (2007) Nocturnal male sex drive in DrosophilaCurr. Biol.  17, 244-251.
  8. Tanoue, S., A. Chatterjee, P. Krishnan and P. E. Hardin (2008) G-protein-coupled Receptor Kinase 2 is required for rhythmic olfactory responses in DrosophilaCurr. Biol. 18, 787-794.
  9. Krishnan, P., A. Chatterjee and P. E. Hardin (2008) Spike amplitude and single unit responses in antennal sensillae is controlled by the Drosophila circadian clock. Curr. Biol. 18, 803-807.
  10. Chatterjee, A., G. Roman and P. E. Hardin (2009) Go contributes to olfactory reception in Drosophila melanogasterBMC Physiology 9, 22.
  11. Chatterjee, A., S. Tanoue, J. H. Houl and P. E. Hardin (2010) Regulation of gustatory physiology and appetitive behavior by the circadian clock in Drosophila melanogasterCurr. Biol. 20, 300-309.
  12. Chatterjee, A. and P. E. Hardin (2010) Time to taste: Circadian clock function in the Drosophila gustatory system. FLY 4, 283-287.
  13. Zhang, Y., Y. Liu, D. Wentworth, P. E. Hardin and P. Emery (2010) Light and temperature control the contribution of a subset of Dorsal Neurons 1 to Drosophila circadian behavior. Curr. Biol. 20, 591-599.
  14. Zhang, L., B. Y. Chung, B. C. Lear, V. L. Kilman, Y. Liu, G. Mahesh, R. Meissner, P. E. Hardin and R. Allada (2010) A subset of circadian neurons coordinates light and PDF signaling to produce robust daily behavior in Drosophila. Curr. Biol.  20, 600-605.
  15. Kaneko, H., L. M. Head, J. Ling, Y. Liu, P. E. Hardin, P. Emery, F. N. Hamada (2012) Circadian rhythm of temperature preference and its neural control in Drosophila. Curr. Biol. 22, 1851-1857.
  16. Agrawal, P., J. H. Houl, K. Gunawardhana, T. Liu, J. Zhou, Mark J. Zoran and Paul E. Hardin (2017) Drosophila CRY entrains clocks in body tissues to light and maintains passive membrane properties in a non-clock body tissue independent of light. Curr Biol., in press.
  17. Chatterjee A, A. Lamaze A., J. De, E. Chelot, B. Martin, P. E. Hardin, S. Kadener, P. Emery and F. Rouyer (2017) Reconfiguring a multi-oscillator network by light in the Drosophila circadian clock. Submitted.