Jeffrey Hall has retired. A description of his previous research at Brandeis University follows:
I and my colleagues investigate the function of the nervous
system in Drosophila. Many of our approaches involve genetic
studies of behavior, augmented in by molecular manipulations
of genes defined by certain behavioral mutations. These
investigations are in two areas:
MOLECULAR NEUROGENETICS OF COURTSHIP
How is Drosophila's central nervous system programmed to
control elements of the flies' reproductive behaviors? Our
earlier studies that addressed this question involved identification
of pertinent portions of the adult CNS, using "sex mosaics"
and disruptions of these tissues, using mutants specifically
defective in the metabolism of a centrally acting neurotransmitter,
We are currently focusing most of our attention on courtship
mutants. One is defined by genetic changes at the fruitless (fru) locus, which cause males not to mate with females
and anomalously to court other males. The genetics of fru are as complicated as the syndrome of behavioral abnormalities.
We hope to unravel some of these complexities by virtue
identifying the fru at the molecular level. These
and other neurobiological findings on the fru gene
and its mutants have led to the demonstration that this
factor acts within Drosophila's "sex-determination hierarchy"
(SDH) and defines a new branch of it. In this context, fru,
like certain other SDH genes, encodes a transcription factor.
We recently discovered that production of serotonin (5HT),
in certain of the many neurons that express male-specific
forms of FRU protein, is regulated by the action of this
gene. Moreover, the 5HT neuromodulator seems to regulate
functions of male reproductive organs, which are dramatically
perturbed in certain fru mutants.
Two other courtship mutants were isolated because of abnormal
male "singing" behavior: cacophony (cac)
and dissonance (diss) males generate
aberrant sounds from the wing vibrations they direct at
females. To approach an understanding of how these species-specific
courtship songs are programmed into the fly, we are carrying
out high resolution analyses of mutant vs. normal sounds.
Genetic studies of the cac and diss loci imply
complexities analogous to those associated with fru.
For example, complementation analyses and molecular expression
assessments indicate that both song genes are involved in
the control of visually mediated responses made by the adult
fly (as monitored behaviorally and physiologically). The cac gene encodes a voltage-regulated calcium channel
(a1 subunit). This rationalizes
at least the courtship-song defect in the cac mutant.
The diss mutation is a variant of the nonA gene, which was defined originally by visual mutants and
encodes an RNA-binding protein (NONA). We hypothesize that
NONA inflouences post-transcriptional processing of the
primary cac transcript. Indeed, there are several
different isoforms of that mRNA, resulting from alternative
splicing and RNA editing.
The rate at which Drosophila males generate the "tone pulse"
components of their courtship song varies rhythmically.
The cycle durations are short, ranging from about a half-minute
to a minute-and-a-half, depending on the species. In one
of these, D. melanogaster, circadian rhythm mutations
at the period (per) locus cause song rhythm
abnormalities that parallel the defects in "daily" rhythm
phenotypes. These song findings provided entrées into our
more extensive studies of biological rhythms.
MOLECULAR NEUROGENETICS OF BIOLOGICAL RHYTHMS
We initiated molecular studies of circadian rhythms by
analyzing the per gene, in collaboration with Michael
Rosbash at Brandeis University. Through the 1990s, these
investigations expanded to molecular and neurobiological
experiments revolving round five additional rhythm-related
genes in Drosophila, which were either cloned by others
[timeless (tim)] or by us [Clock (Clk), cycle (cyc), and cryptochrome (cry), and pigment-dispersing factor (pdf)].
The various molecular-neuro-chronobiological investigations
- determination and manipulation (for bioasssays) of these
genes' informational content
- in-vitro manipulations of clock genes or portions thereof--aimed
in part at assessing the expression patterns of these
genes at different stages of the life cycle and in a variety
of neural and non-neural tissues; these studies have included
experimental identification of the neuronal pacemaker
cells underlying the fly's behavioral circadian rhythms
- studies of environmental inputs to the circadian pacemaker,
as mediated in part by cry function (which may
be principally concerned with blue-light reception, but
also seems connected to actual pacemaker operation), and
probably by Clk and cyc as well (these are
mainly clock factors, but the mutants also exhibit abnormal
light-responsiveness in the context of daily rest-activity
- manipulation of the pdf gene, which in Drosophila
does not encode literally a pigment-dispersing factor--instead,
an oligopeptide found only in the CNS; these experiments
showed (to a first approximation) how PDF participates
in output functions of the circadian clock, those underlying
the flies' sleep-wake cycles
- comparison of the structure and function of clock genes
in closely vs. distantly related Drosophila species; these
data have revealed, for example that certain coding regions
are highly conserved and others very diverged, among the
different species; such findings led to interspecific
transfer experiments, in which the effects of all or part
of a donor species' per gene have been bioassayed
in D. melanogaster hosts
To identify additional clock-related genes that contribute
to the overall mechanism of circadian pacemaking, we have
been searching for new rhythm variants. One way of detecting
such factors has involved testing flies carrying transgenes
in which we fused parts of clock genes to a reporter factor--firefly
luciferase (luc). This allows per- and tim-controlled
molecular rhythms to be tracked in real time, in flies that
are individually monitored for "glow cycling" over the course
of several days. The initial fruits of luc-based
screening for molecularly defective rhythm variants included
two new mutations at the tim locus (which confirmed
the validity of this approach) and genetic identification
of a novel chronobiological factor, cry.
Hall J.C. (2000) Cryptochrome: sensory reception, transduction
and clock functions subserving circadian systems. Curr.
Opin. Neurobiol. 10: 456-466. [abstract]
Park J.H., Helfrich-Förster C., Lee G.H., Liu L.,
Rosbash M., and Hall J.C. (2000) Differential regulation
of circadian pacemaker output by separate clock genes in Drosophila. Proc. Nat. Acad. Sci. U.S. 97:
Emery P., Stanewsky R., Hall J.C., and Rosbash M. (2000)
A unique circadian-rhythm photoreceptor. Nature 404:
Emery P., Stanewsky R., Helfrich-Föster C., Emery-Le M.,
Hall J.C., and Rosbash M. (2000) Drosophila CRY is
a deep brain circadian photoreceptor. Neuron 26:493-504.
Kaneko M., and Hall J.C. (2000) Neuroanatomy of cells
expressing clock genes in Drosophila: transgenic
manipulation of the period and timeless genes
to mark the perikarya of circadian pacemaker neurons and
their projections. J. Comp. Neurol. 422: 66-94. [abstract]
Goodwin S.F., Taylor B.J. Villella A., Foss M., Ryner L.C.,
Baker B.S., and Hall J.C. (2000) Mutations in the fruitless gene of Drosophila melanogaster causing aberrant
splicing or altered spatial distributions of fru's
sex-specific expression patterns. Genetics 154: 725-745.
Lee G., Foss M., Goodwin S.F., Carlo T., Taylor B.J., and
Hall J.C. (2000) Spatial, temporal, and sexually dimorphic
expression patterns of the fruitless gene in the Drosophila CNS. J. Neurobiol. 43: 404-426.
Lee G., and Hall J.C. (2001) Abnormalities of male-specific
FRU protein and serotonin expression in the central nervous
system of fruitless mutants in Drosophila.
J. Neurosci.21: 513-526.
Lee G., Villella A., Taylor B.J., and Hall J.C. (2001)
New reproductive anomalies in fruitless-mutant Drosophila males: extreme lengthening of mating durations and infertility
correlated with defective serotonergic innervation of reproductive
organs. J. Neurobiol. 47: 121-149. [abstract]
Baker B.S., Taylor B.J., and Hall J.C. (2001) Are complex
behaviors specified by dedicated regulatory genes? Reasoning
from Drosophila. Cell 105: 13-24. [abstract]
Helfrich-Forster C., Winter C., Hofbauer A., Hall J.C.,
and Stanewsky R. (2001) The circadian clock of Drosophila is blind after elimination of all known photoreceptors.
Neuron. 30: 249-261. [abstract]
Krishnan B., Levine J.D., Lynch K.S., Dowse H.B., Funes
P., Hall J.C., Hardin P.E., and Dryer S.E. (2001) A novel
role for cryptochrome in a Drosophila circadian oscillator.
Nature. 411: 313-317. [abstract]
Campesan S., Dubrova Y., Hall J.C., and Kyriacou C.P. (2001)
The nonA gene in Drosophila conveys species-specific
behavioral characteristics. Genetics 158: 1535-1543.
Stempfl, T., Vogel M., Szabo G., Wülbeck C., Liu J., Hall
J.C., and Stanewsky R. (2002) Identification of circadian-clock
regulated enhancers and genes of Drosophila melanogaster by transposon mobilization using firefly luciferase as a
reporter. Genetics 160: 571-593. [abstract]
Chan B., Villella A., Funes P., and Hall J.C. (2002) Courtship
and other behaviors affected by a heat-sensitive, molecularly
novel mutation in the cacophony calcium-channel gene
of Drosophila. Genetics 162: 135-153. [abstract]
Levine J.D., Funes P., Dowse H.B., and Hall J.C. (2002)
Resetting the circadian clock by social experience in Drosophila melanogaster. Science 298: 2010-2012.
Hall J.C. (2003) Genetics and molecular biology of rhythms
in Drosophila and other insects. Adv. Genet. 48:
Peng Y., Stoleru D., Levine J.D., Hall J.C., and Rosbash
M. (2003) Drosophila free-running rhythms require
intercellular communication. Pub. Lib. Sci. Biol. 1:
Hall J.C. (2003) A neurogeneticist's manifesto. J. Neurogenet. 17:1-90.
Veleri S., Brandes C., Helfrich-Förster C., Hall J.C.,
and Stanewsky R. (2003) A self-sustaining, light-entrainable
circadian oscillator in the brain of Drosophila.
Curr. Biol. 13: 1758-1767.
Shafer O., Levine J.D., Truman J.W., and Hall J.C. (2004)
Flies by night: effects of changing day length on Drosophila's circadian clock. Curr. Biol. 14: 424-432.
Choi Y., Lee G., Hall J.C., and Park J.H. (2005) Cloning
and expression analysis of corazonin-encoding genes in Drosophila species and functional insights into corazonin-expressing
neurons. J. Comp. Neurol. 482: 372-385.
Hall J.C. (2005) Systems approaches to biological rhythms
in Drosophila. Methods Enzymol. 393: 61-185.
Manoli D.S., Foss M., Villella A., Taylor B.J., Hall J.C.,
and Baker B.S. (2005) Male-specific fruitless specifies
the neural substrates of Drosophila courtship behaviour.
Nature 436: 395-400.
Villella A., Ferri S.L., Krystal J.D., and Hall J.C. (2005)
Functional analysis of fruitless gene expression
by transgenic manipulations of Drosophila courtship.
Proc. Nat. Acad. Sci. U.S. 102: 16550-16557. [abstract]
Kadener S, Villella A, Kula E, Palm K, Pyza E, Botas J,
Hall JC, Rosbash M. (2006) Neurotoxic protein expression
reveals connections between the circadian clock and mating
behavior in Drosophila. Proc Natl Acad Sci U S
A. 2006 Sep 5;103:13537-42. Epub 2006 Aug 28.
Villella A, Peyre JB, Aigaki T, Hall JC. (2006) Defective
transfer of seminal-fluid materials during matings of semi-fertile
fruitless mutants in Drosophila .J Comp Physiol
A Neuroethol Sens Neural Behav Physiol. 2006 Dec;192:1253-69.
Epub 2006 Aug 1. [abstract]
View Complete Publication List on PubMed: Jeff Hall
Last review: March 21, 2007