The Development of Neural
Circuits and Behavior in the Embryo of Drosophila
There have been great advances in our
knowledge of the way in which the nervous system develops
in the last few decades. We now begin to understand
how nerve cells are made, how growing axons are guided,
and how connections are formed. However, at least one
great area of neuronal development remains relatively
unexplored: the development of the circuitry underlying
movement and the maturation of coordinated patterns
of locomotion in embryos. We have chosen to work on
the development of larval movement patterns in the embryo
of the fruit fly Drosophila using this as a model
for the development of motor circuitry and behavior.
The overall goal is to be able to write down the principles
for genetically specifying and assembling the elements
of a motor system. A simple pattern of peristaltic contractions
develops in the late Drosophila embryo and it
is the posterior to anterior passage of a wave of such
contractions that enables the newly hatched larva to
move forwards over the substrate. An important point
can be quickly established in the Drosophila
embryo: mis-expression of toxins and a mutant ion channel
in sensory neurons shows that the peristaltic motor
system can be constructed without sensory input. This
work demonstrates a fundamental point, namely that a
motor pattern and the central pattern generator that
produces it can develop without 15 sensory feedback.
It is also a useful simplification: it shows that the
development of the system is an autonomous property
of the neurons that comprise the central pattern generator
and allows us to focus our future analysis on these
cells and their properties.
How are the cells of the motor system
organized? We can label all of the motorneurons concerned
and we find that their dendrites (the branches that
receive synaptic input in the central nervous system)
are organized in a highly predictable spatial array.
This pattern of neuronal branches is a faithful replica
in the brain of the pattern of innervated muscles in
the periphery—we call this a myotopic map in comparison
to the somatotopic maps of sensory endings that are
also formed in the developing nervous system. Interestingly,
the myotopic maps of the muscles are organized in register
with the body segmentation, suggesting that they represent
a fundamental way of partitioning neuronal connectivity
comparable to the segmental body plan of the insect.
Our experiments show that the development of the map
is once again an autonomous property of the motor neurons
and does not depend on the muscles. It is clearly essential
to begin to understand how the pattern synaptic contacts
on the motor neuron dendrites are organized as the system
develops. Our experiments show that these synapses are
made by neurons that use acetylcholine as a neurotransmitter
but the identity of the cells concerned is still unclear.
As a model for understanding presynaptic development
in the central nervous system we have looked at the
endings of distinct subsets of sensory neurons within
the developing brain. We find that termination sites
are determined independently of target neurons and can
be respecified by the expression of inappropriate transcription
factors in the presynaptic cells. It appears that a
system of signals within the embryonic nervous system
provides a set of coordinates that guide growing axons
to particular termination sites, independently of their
targets, but depending on the particular constellation
of receptors for signaling molecules that each neuron
expresses. We propose that in this first phase of target
independent termination and branching, pre- and postsynaptic
partner neurons are delivered to a common region of
neuropile. This is an economical mechanism for providing
an initial platform from which actual patterns of connectivity
are formed in a subsequent, putatively activity- dependent
phase of development. It is these patterns of connectivity
between pre- and postsynaptic neurons that are at the
heart of the developing motor system that we seek to
understand.
