7.1 Extending the Network: Arising Questions
In the previous chapters, I have asked two questions: (1) What are the
mechanisms that shape the elements of neuromuscular networks? (2) What are the
cues that underlie these mechanisms? I have characterised differences between
the pattern of muscles (Chapter 2) and neurons (Chapter 3) and related pairs of
muscles and neurons among different segments to explore alterations (Chapters 4
I have demonstrated that several mechanisms lead to such alterations specific
for A8/9: the number of myoblasts recruited through muscle founder cells,
suppression of muscle formation and positioning of muscle progenitors all
contribute to the diversification of the muscle pattern. I have also found cases
in which related muscles express different transcription factors; in some cases,
these muscles are innervated by different motorneurons, in others by
motorneurons with altered dendrite morphology. “Supernumerary” neurons with no
target muscle in A8/9 die. I could also present evidence that most, if not all,
of these mechanisms are determined by the expression of Hox genes, most
importantly Abd-B (Chapter 6).
I have discussed the findings of my experiments after each chapter. In the
following, I will concentrate on the questions that have arisen through my work
and suggest future directions for further research.
In my work, I have focussed exclusively on muscles and motorneurons. The
locomotor machinery of the larva, however, comprises of more than these two cell
types and includes denticles, tendons, interneurons and sensory neurons. Each of
these elements could be altered through elimination, lineage changes or an
The altered position of LT1 in A8 compared to VT1 in the reference segment
suggests an altered pattern of tendon cells in this segment, which anchor the
muscle precursors to the bodywall. The denticle band of A9 is strongly altered
with respect to all anterior segments of the abdomen. The size of neuromuscular
junctions could be altered to accommodate a different role of the muscle.
I have hypothesised that the neuromuscular network of A8/9 is different to the
reference segment because it serves different functions. Some specialised
structures are located there, including the anal slit, the anal pad and the
posterior spiracles. Such structures are likely to be controlled by some of the
muscles in A8/9. Appropriate coordination of these muscles presumably requires
alterations in the nervous system, from sensory input to interneuronal circuits.
It is worth noting that there are sensory organs just lateral of the anal slit.
With respect to the reference segment, this is a specialisation that could be
investigated to relate alterations in sensory input with motor output.
Investigating the role of individual muscles in a particular behaviour could be
done through laser ablation in combination with behavioural assays.
My experiments implicating Hox gene expression as a crucial factor for
mechanisms of diversification open up many questions particularly concerning the
direct action of Hox proteins. More detailed research on the molecular
interactions that execute the described mechanisms will show that my two
questions (What are the mechanisms of diversification? What are cues underlying
them?) can be merged to one on the level of molecular development: Hox proteins
and their cofactors regulate and co-ordinate the transcription of proteins that
are in turn elements of developmental pathways leading to the formation of
The differentiation of the early aCC into two distinct cells in the reference
segment and A8, from where they innervate muscles DA1 and GS4 respectively,
provides us with a system of two functionally and morphologically distinct
motorneurons whose lineage is resolved. Therefore, aCC gives a striking
demonstration of how far variation and plasticity can go on the level of
equivalent motorneurons. The detailed knowledge of the development of aCC makes
the segment-specific differentiation of this cell an excellent system to study
key questions of diversification. I described the extent of the diversification,
but the factors regulating the two different fates remain to be resolved.
In this context, one should note that aCC is not only a well-characterised
motorneuron that is very accessible for both genetic and mechanical
manipulation; it is also known in a variety of insect species. It was first
described in the grasshopper Schistocerca (GOODMAN et al., 1982), where its
development can be followed from early stages and traced to neuroblast 1-1
(BROADUS et al., 1995). Thereby, aCC opens a window to the starting point of my
project: a comparative investigation of the diversification mechanisms shaping
neuromuscular networks in different species of arthropods. This requires
research in equivalent (homologous) cells, just like aCC.
In this system, one could now compare a Drosophila aCC from the reference
segment, a Drosophila aCC from A8 and a homologous aCC in a different arthropod
species and expand the questions of this thesis beyond Drosophila: What features
of these cells are different and by which mechanisms are these differences
shaped over the course of development? The investigation of different arthropod
species could eventually allow the reconstruction of an ancestral “ground state”
of aCC and its muscle target.
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