Circadian rhythms are the daily cycles of biomedical,
physiological, and behavioral activities exhibited by
many species from microorganisms to humans. The fundamental
properties of this system are the following: the rhythms
persist in constant environmental conditions such as constant
light and constant temperature; the period of a rhythmic
activity in a constant condition is approximately 24 hours,
and this period is constant over a relatively wide range
of temperature, and phases of these rhythms can be reset
by an environmental stimulus such as a brief light pulse.
These properties of the circadian systems are remarkably
similar in organisms as diverse as plants and mammals.
However, some organisms are suitable for studies at the
level of tissue, and others are more suitable at the level
of cellular and molecular studies. For instance in vertebrates,
anatomical locations of the circadian pacemaker tissues
have been studied intensively by surgical studies. While
these surgical studies were successful in defining pacemaker
structures, identification of the pacemaker cells within
a structure was difficult.
In Drosophila, studies of circadian rhythms have
been mainly at the molecular level rather than at the
cellular or tissue level. Several genes that are involved
in the pacemaking mechanism of the circadian clock have
been identified. Recently, homologues of these molecular
mechanisms of the circadian clock genes have been isolated
in humans and mouse, suggesting a similarity in the molecular
mechanisms of the circadian clock in insects and in mammals.
Among these genes, the period (per) and timeless
(tim) genes have been studied intensively in flies.
This made it possible to define the locations of putative
pacemaker cells in this organism by monitoring spatial
and temporal expression patterns of RNA and protein products
of these genes. Numerous cells were found to express per
and tim cyclically throughout the body of the fly.
While many of these cells are putative pacemaker cells
of unknown physiological function, some of the neurons
in the brain are involved in the rhythmicity of fly's
locomotor activity.
The first part of my work was focused on the expression
patterns of per and tim proteins in brains
of developing fruit flies. In the putative pacemaker brain
neurons, these proteins oscillate in their amount. Surprisingly,
the oscillations of these proteins in different cells
were out-of phase. This result implies the presence of
multiple oscillators involved in rhythms of different
physiological or behavioral processes in a single organism.
The second part of my work is anatomical characterization
of the wiring patterns of the pacemaker neurons. This
study gives an insight into the pathways from the pacemaker
neurons to various tissues that are involved in circadian
outputs.
