Genetic and molecular analysis of circadian rhythms in Neurospora.

Over the course of the past 40 years Neurospora has become a well-known and uniquely tractable model system for the analysis of the molecular basis of eukaryotic circadian oscillatory systems. Molecular bases for the period length and sustainability of the rhythm, light, and temperature resetting of the circadian system and for gating of light input and light effects are becoming understood, and Neurospora promises to be a suitable system for examining the role of coupled feedback loops in the clock. Many of these insights have shown or foreshadow direct parallels in mammalian systems, including the mechanism of light entrainment, the involvement of PAS:PAS heterodimers as transcriptional activators in essential clock-associated feedback loops, and dual role of FRQ in the loop as an activator and a repressor; similarities extend to the primary sequence level in at least one case, that of WC-1 and BMAL1. Work on circadian output in Neurospora has identified more than a dozen regulated genes and has been at the forefront of studies aimed at understanding clock control of gene expression.

[1]  J. Paietta,et al.  Isolation and characterization of light-insensitive mutants of Neurospora crassa. , 1983, Genetics.

[2]  J. F. Feldman,et al.  Temperature Compensation of Circadian Period Length in Clock Mutants of Neurospora crassa. , 1981, Plant physiology.

[3]  D. Ebbole,et al.  Analysis of two transcription activation elements in the promoter of the developmentally regulated con-10 gene of Neurospora crassa. , 1998, Fungal genetics and biology : FG & B.

[4]  Till Roenneberg,et al.  Assignment of circadian function for the Neurospora clock gene frequency , 1999, Nature.

[5]  C. Yanofsky,et al.  Day/night and circadian rhythm control of con gene expression in Neurospora. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[6]  I. Edery,et al.  The Drosophila CLOCK Protein Undergoes Daily Rhythms in Abundance, Phosphorylation, and Interactions with the PER–TIM Complex , 1998, Neuron.

[7]  J. Dunlap,et al.  Nuclear localization is required for function of the essential clock protein FRQ , 1998, The EMBO journal.

[8]  P. Lakin-Thomas.  Circadian rhythms: new functions for old clock genes. , 2000, Trends in genetics : TIG.

[9]  S. Honma,et al.  Circadian oscillation of BMAL1, a partner of a mammalian clock gene Clock, in rat suprachiasmatic nucleus. , 1998, Biochemical and biophysical research communications.

[10]  M. Merrow,et al.  How temperature changes reset a circadian oscillator. , 1998, Science.

[11]  J. Dunlap,et al.  Phosphorylation of the Neurospora clock protein FREQUENCY determines its degradation rate and strongly influences the period length of the circadian clock. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  C S Pittendrigh,et al.  Temperature compensation of the circadian oscillation in drosophila pseudoobscura and its entrainment by temperature cycles. , 1968, Journal of insect physiology.

[13]  K. Onai,et al.  Mutation of the cys-9 gene, which encodes thioredoxin reductase, affects the circadian conidiation rhythm in Neurospora crassa. , 1997, Genetics.

[14]  J. Dunlap,et al.  Neurospora crassa clock-controlled genes are regulated at the level of transcription , 1991, Molecular and cellular biology.

[15]  Jeffrey C. Hall,et al.  CYCLE Is a Second bHLH-PAS Clock Protein Essential for Circadian Rhythmicity and Transcription of Drosophila period and timeless , 1998, Cell.

[16]  D D Perkins,et al.  Perspectives Anecdotal , Historical and Critical Commentaries on Genetics , 2002 .

[17]  H. Nakashima,et al.  Assay and Characteristics of Circadian Rhythmicity in Liquid Cultures of Neurospora crassa. , 1981, Plant physiology.

[18]  J. Loros,et al.  A recessive circadian clock mutation at the frq locus of Neurospora crassa. , 1986, Genetics.

[19]  D. Stadler.  Growth Patterns in Neurospora: Genetic Control of a Cyclic Growth Pattern in Neurospora , 1959, Nature.

[20]  J. Loros,et al.  Loss of Temperature Compensation of Circadian Period Length in the frq-9 Mutant of Neurospora crassa , 1986, Journal of biological rhythms.

[21]  S. Brody,et al.  Circadian rhythms in Neurospora crassa: oscillations in fatty acids. , 1982, Biochemistry.

[22]  P Ruoff,et al.  The Goodwin Oscillator: On the Importance of Degradation Reactions in the Circadian Clock , 1999, Journal of biological rhythms.

[23]  M. Springer.  Genetic control of fungal differentiation: The three sporulation pathways of Neurospora crassa , 1993, BioEssays : news and reviews in molecular, cellular and developmental biology.

[24]  C. Yanofsky,et al.  Isolation and characterization of genes differentially expressed during conidiation of Neurospora crassa , 1985, Molecular and cellular biology.

[25]  D. Bell-Pedersen,et al.  Distinct cis-acting elements mediate clock, light, and developmental regulation of the Neurospora crassa eas (ccg-2) gene , 1996, Molecular and cellular biology.

[26]  P. Hardin,et al.  Interlocked feedback loops within the Drosophila circadian oscillator. , 1999, Science.

[27]  P. Decoursey,et al.  Behavior of SCN-Lesioned Chipmunks in Natural Habitat: A Pilot Study , 1998, Journal of biological rhythms.

[28]  A. Sussman,et al.  MORPHOLOGY AND GENETICS OF A PERIODIC COLONIAL MUTANT OF NEUROSPORA CRASSA , 1964 .

[29]  J. Dunlap,et al.  Genetic analysis of circadian clocks. , 1993, Annual review of physiology.

[30]  L. Rensing,et al.  Possible link between circadian rhythm and heat shock response in Neurospora crassa. , 1987, Chronobiology international.

[31]  M. Merrow,et al.  Circadian Systems and Metabolism , 1999, Journal of biological rhythms.

[32]  T. Pavlidis.  Populations of interacting oscillators and circadian rhythms. , 1969, Journal of theoretical biology.

[33]  J. Dunlap.  Molecular Bases for Circadian Clocks , 1999, Cell.

[34]  C. Pittendrigh,et al.  Growth Patterns in Neurospora: A Biological Clock in Neurospora , 1959, Nature.

[35]  D. Bell-Pedersen.  Circadian Rhythms in Neurospora crassa , 2002 .

[36]  H. Nakashima.  A Liquid Culture Method for the Biochemical Analysis of the Circadian Clock of Neurospora crassa , 1981 .

[37]  P Ruoff,et al.  The Goodwin model: simulating the effect of cycloheximide and heat shock on the sporulation rhythm of Neurospora crassa. , 1999, Journal of theoretical biology.

[38]  L. Rensing,et al.  Differential expression of glucose-regulated (grp78) and heat-shock-inducible (hsp70) genes during asexual development of Neurospora crassa. , 1998, Microbiology.

[39]  M. Sargent,et al.  Effects of temperature perturbations on circadian conidiation in neurospora. , 1979, Plant physiology.

[40]  J. F. Feldman,et al.  Isolation and characterization of a temperature-sensitive circadian clock mutant of Neurospora crassa. , 1997, Genetics.

[41]  D. Bell-Pedersen,et al.  Circadian clock-controlled genes isolated from Neurospora crassa are late night- to early morning-specific. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[42]  J. Takahashi,et al.  Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. , 2000, Science.

[43]  D Gonze,et al.  Theoretical models for circadian rhythms in Neurospora and Drosophila. , 2000, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[44]  W. Briggs,et al.  The effects of light on a circadian rhythm of conidiation in neurospora. , 1967, Plant physiology.

[45]  P. Lakin-Thomas.  Effects of Choline Depletion on the Circadian Rhythm in Neurospora crassa , 1996 .

[46]  J. F. Feldman,et al.  Genetic and physiological characteristics of a slow-growing circadian clock mutant of Neurospora crassa. , 1978, Genetics.

[47]  H. Nakashima,et al.  Mutants with altered sensitivity to a calmodulin antagonist affect the circadian clock in Neurospora crassa. , 1996, Genetics.

[48]  M. Werner-Washburne,et al.  Expressed sequences from conidial, mycelial, and sexual stages of Neurospora crassa. , 1997, Fungal genetics and biology : FG & B.

[49]  S. Reppert,et al.  Molecular analysis of mammalian circadian rhythms. , 2001, Annual review of physiology.

[50]  C. Yanofsky,et al.  Developmental and light regulation of eas, the structural gene for the rodlet protein of Neurospora. , 1992, Genes & development.

[51]  Yi Liu,et al.  Thermally Regulated Translational Control of FRQ Mediates Aspects of Temperature Responses in the Neurospora Circadian Clock , 1997, Cell.

[52]  D. Mattern.  Unsaturated fatty acid isomers: effects on the circadian rhythm of a fatty-acid-deficient Neurospora crassa mutant. , 1985, Archives of biochemistry and biophysics.

[53]  M. Sargent,et al.  Circadian Rhythms in Neurospora , 1973 .

[54]  J. Dunlap,et al.  An End in the Beginning , 1998, Science.

[55]  K. Yagita,et al.  A new mammalian period gene predominantly expressed in the suprachiasmatic nucleus , 1998, Genes to cells : devoted to molecular & cellular mechanisms.

[56]  D. Sidote,et al.  Differential Effects of Light and Heat on theDrosophila Circadian Clock Proteins PER and TIM , 1998, Molecular and Cellular Biology.

[57]  J. Paietta,et al.  Photoreception in Neurospora crassa: correlation of reduced light sensitivity with flavin deficiency. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[58]  P. Lakin-Thomas,et al.  sn-1,2-diacylglycerol levels in the fungus Neurospora crassa display circadian rhythmicity. , 2000, The Journal of biological chemistry.

[59]  W. H. Brandt.  Zonation in a Prolineless Strain of Neurospora , 1953 .

[60]  A. Millar,et al.  Circadian biology: Clocks for the real world , 1999, Current Biology.

[61]  L. A. Sawyer,et al.  Natural variation in a Drosophila clock gene and temperature compensation. , 1997, Science.

[62]  D. Bell-Pedersen,et al.  The Neurospora circadian clock-controlled gene, ccg-2, is allelic to eas and encodes a fungal hydrophobin required for formation of the conidial rodlet layer. , 1992, Genes & development.

[63]  G. Macino,et al.  Role of a white collar‐1–white collar‐2 complex in blue‐light signal transduction , 1999, The EMBO journal.

[64]  Erwin Bünning,et al.  The Physiological Clock , 1964, Heidelberg Science Library.

[65]  J. F. Feldman.  Genetic Approaches to Circadian Clocks , 1982 .

[66]  J. Hogenesch,et al.  The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Gregor Eichele,et al.  A Differential Response of Two Putative Mammalian Circadian Regulators, mper1 and mper2, to Light , 1997, Cell.

[68]  M. Sargent,et al.  Circadian Rhythms of Nucleic Acid Metabolism in Neurospora crassa , 1974, Journal of bacteriology.

[69]  Peter Ruoff,et al.  Modeling temperature compensation in chemical and biological oscillators. , 1997, Chronobiology international.

[70]  G. Macino,et al.  Light and development regulate the expression of the albino-3 gene in Neurospora crassa. , 1995, Developmental biology.

[71]  Mark J. Zylka,et al.  Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei , 1997, Neuron.

[72]  V. Gooch,et al.  Temperature Effects on the Resetting of the Phase of the Neurospora Circadian Rhythm , 1994, Journal of biological rhythms.

[73]  P. Lakin-Thomas.  Choline Depletion, frq Mutations, and Temperature Compensation of the Circadian Rhythm in Neurospora crassa , 1998, Journal of biological rhythms.

[74]  S. Brody,et al.  Circadian rhythms in Neurospora crassa: a mutation affecting temperature compensation. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[75]  J. Dunlap,et al.  Neurospora wc-1 and wc-2: transcription, photoresponses, and the origins of circadian rhythmicity. , 1997, Science.

[76]  J. Dunlap,et al.  Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. , 1994, Science.

[77]  J. Besharse,et al.  Identification of a novel vertebrate circadian clock-regulated gene encoding the protein nocturnin. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[78]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[79]  A. Winfree.  Acute temperature sensitivity of the circadian rhythm in Drosophila , 1972 .

[80]  M. W. Young,et al.  double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation , 1998, Cell.

[81]  H. Iwasaki,et al.  Microbial circadian oscillatory systems in Neurospora and Synechococcus: models for cellular clocks. , 2000, Current opinion in microbiology.

[82]  G. Macino,et al.  Involvement of protein kinase C in the response of Neurospora crassa to blue light , 1999, Molecular and General Genetics MGG.

[83]  G. Macino,et al.  Blue light regulation in Neurospora crassa. , 1997, Fungal genetics and biology : FG & B.

[84]  S. Kay,et al.  Integration of circadian and phototransduction pathways in the network controlling CAB gene transcription in Arabidopsis. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[85]  J. Dunlap,et al.  Glyceraldehyde-3-phosphate Dehydrogenase Is Regulated on a Daily Basis by the Circadian Clock* , 1998, The Journal of Biological Chemistry.

[86]  J. Dunlap,et al.  Interconnected feedback loops in the Neurospora circadian system. , 2000, Science.

[87]  K. Onai,et al.  Spermidine Determines the Sensitivity to the Calmodulin Antagonist, Chlorpromazine, for the Circadian Conidiation Rhythm but Not for the Mycelial Growth in Neurospora crassa , 1998, Journal of biological rhythms.

[88]  N. Talbot.  Fungal biology: Coming up for air and sporulation , 1999, Nature.

[89]  J. Dunlap,et al.  Isolation and analysis of the arg-13 gene of Neurospora crassa. , 1996, Genetics.

[90]  K. Onai,et al.  Mutation of the gene for the second-largest subunit of RNA polymerase I prolongs the period length of the circadian conidiation rhythm in Neurospora crassa , 1998, Molecular and General Genetics MGG.

[91]  C. Diekmann,et al.  Circadian rhythms in Neurospora crassa: oligomycin-resistant mutations affect periodicity. , 1980, Science.

[92]  E. Koonin,et al.  Pineal Serotonin N-Acetyltransferase: Expression Cloning and Molecular Analysis , 1995, Science.

[93]  J. Dunlap,et al.  Circadian clock locus frequency: protein encoded by a single open reading frame defines period length and temperature compensation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Yi Liu,et al.  Alternative Initiation of Translation and Time-Specific Phosphorylation Yield Multiple Forms of the Essential Clock Protein FREQUENCY , 1997, Cell.

[95]  J. F. Feldman,et al.  The frq locus in Neurospora crassa: a key element in circadian clock organization. , 1980, Genetics.

[96]  A. Halpern,et al.  Large-scale comparison of fungal sequence information: mechanisms of innovation in Neurospora crassa and gene loss in Saccharomyces cerevisiae. , 2000, Genome research.

[97]  D. Ebbole,et al.  Tissue-specific repression of starvation and stress responses of the Neurospora crassa con-10 gene is mediated by RCO1. , 1998, Fungal genetics and biology : FG & B.

[98]  S. Brody,et al.  Circadian rhythms in Neurospora crassa: effects of unsaturated fatty acids , 1979, Journal of bacteriology.

[99]  S. Golden,et al.  Resonating circadian clocks enhance fitness in cyanobacteria. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[100]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[101]  K. Onai,et al.  The circadian conidiation rhythm inNeurospora crassa , 1996 .

[102]  P. Lakin-Thomas,et al.  Circadian rhythms in Neurospora crassa: biochemistry and genetics. , 1990, Critical reviews in microbiology.

[103]  J. Dunlap,et al.  Molecular cloning of genes under control of the circadian clock in Neurospora. , 1989, Science.

[104]  J. F. Feldman,et al.  Isolation of circadian clock mutants of Neurospora crassa. , 1973, Genetics.

[105]  D. Sidote,et al.  Circadian Regulation of a Drosophila Homolog of the Mammalian Clock Gene: PER and TIM Function as Positive Regulators , 1998, Molecular and Cellular Biology.

[106]  C. Kyriacou,et al.  Conceptual translation of timeless reveals alternative initiating methionines in Drosophila. , 1997, Nucleic acids research.

[107]  P. Lakin-Thomas,et al.  Circadian rhythms in Neurospora crassa: lipid deficiencies restore robust rhythmicity to null frequency and white-collar mutants. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[108]  M. Sargent,et al.  Rhythms of Enzyme Activity Associated with Circadian Conidiation in Neurospora crassa , 1974, Journal of bacteriology.

[109]  M. Sargent,et al.  Effects of medium composition and carbon dioxide on circadian conidiation in neurospora. , 1972, Plant physiology.

[110]  Gregor Eichele,et al.  RIGUI, a Putative Mammalian Ortholog of the Drosophila period Gene , 1997, Cell.

[111]  Yoshiyuki Sakaki,et al.  Circadian oscillation of a mammalian homologue of the Drosophila period gene , 1997, Nature.

[112]  M. Merrow,et al.  Dissection of a circadian oscillation into discrete domains. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[113]  K. Münger,et al.  The Neurospora crassa metallothionein gene. Regulation of expression and chromosomal location. , 1987, The Journal of biological chemistry.

[114]  G. Macino,et al.  White collar‐1, a central regulator of blue light responses in Neurospora, is a zinc finger protein. , 1996, The EMBO journal.

[115]  V. Russo,et al.  Neurospora crassa blue light-inducible gene bli-3. , 1994, Biochemistry and molecular biology international.

[116]  J. F. Feldman,et al.  A Direct Comparison between Circadian and Noncircadian Rhythms in Neurospora crassa. , 1974, Plant physiology.

[117]  J. Wessels,et al.  Fungi in their own right. , 1999, Fungal genetics and biology : FG & B.

[118]  G. Macino,et al.  Roles in dimerization and blue light photoresponse of the PAS and LOV domains of Neurospora crassa white collar proteins , 1998, Molecular microbiology.

[119]  D. Klein,et al.  Chick pineal clock regulates serotonin N-acetyltransferase mRNA rhythm in culture. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[120]  C. Schwerdtfeger,et al.  Localization and light-dependent phosphorylation of white collar 1 and 2, the two central components of blue light signaling in Neurospora crassa. , 2000, European journal of biochemistry.

[121]  Jennifer J. Loros,et al.  Light-induced resetting of a circadian clock is mediated by a rapid increase in frequency transcript , 1995, Cell.

[122]  A. Radford,et al.  Chromosomal loci of Neurospora crassa. , 1982, Microbiological reviews.

[123]  Minoru Tanaka,et al.  Positional Cloning of the Mouse Circadian Clock Gene , 1997, Cell.

[124]  Lily Yan,et al.  Light-Induced Resetting of a Mammalian Circadian Clock Is Associated with Rapid Induction of the mPer1 Transcript , 1997, Cell.

[125]  Paul E. Hardin,et al.  dCLOCK Is Present in Limiting Amounts and Likely Mediates Daily Interactions between the dCLOCK–CYC Transcription Factor and the PER–TIM Complex , 2000, The Journal of Neuroscience.

[126]  S. Kay,et al.  A circadian clock regulates transcription of the wheat Cab 1 gene. , 1988 .

[127]  W. Briggs,et al.  Circadian nature of a rhythm expressed by an invertaseless strain of Neurospora crassa. , 1966, Plant physiology.

[128]  K Kume,et al.  Interacting molecular loops in the mammalian circadian clock. , 2000, Science.

[129]  D. Morse,et al.  Circadian synthesis of a nuclear-encoded chloroplast glyceraldehyde-3-phosphate dehydrogenase in the dinoflagellate Gonyaulax polyedra is translationally controlled. , 1999, Biochemistry.

[130]  G. Macino,et al.  White collar 2, a partner in blue‐light signal transduction, controlling expression of light–regulated genes in Neurospora crassa , 1997, The EMBO journal.

[131]  A. Goldbeter,et al.  Limit Cycle Models for Circadian Rhythms Based on Transcriptional Regulation in Drosophila and Neurospora , 1999, Journal of biological rhythms.

[132]  H. Nakashima,et al.  Isolation of temperature-sensitive rhythm mutant in Neurospora crassa , 1998 .

[133]  M. Rosbash,et al.  The Drosophila takeout Gene Is a Novel Molecular Link between Circadian Rhythms and Feeding Behavior , 2000, Cell.