A major goal in developmental neurobiology is to understand how a large number of different neuronal and glial cell types is generated and assembled into functional circuits. The fruitfly Drosophila melanogaster is one of the favoured model systems used to address this problem. Apart from the availability of sophisticated genetic techniques and the convenient access to online data collections, one major advantage of this model is that analysis can be performed at the level ofsingle, identified cells.
The CNS derives from a stereotype population of neural stem cells (Neuroblasts, NBs), whichdelaminate in the early embryo from the neurogenic region of the ectoderm. NBs generally divide asymmetrically to produce a chain of secondary precursor cells, which generate postmitotic neuronal and/or glial cell types in a specific temporal sequence. Almost all embryonic NBs (brain and ventral nerve cord) have been identified and characterized at a molecular level. The largely invariant cellular lineages generated by these neuroblasts have also been described (in the ventral nerve cord).
The detailed characterization of the wild-type embryonic nervous system is an important basis for the analysis of the mechanisms controlling neural development: it is prerequisite for the interpretation of mutant phenotypes and the effects of experimental manipulations on the level of individual cells or cell lineages.
A specific identity is conferred to each individual NB already in the neuro-ectoderm by the products of segmentation genes, Hox-genes and dorso-ventral patterning genes. NBs deriving from corresponding regions of the neuro-ectoderm in different segments express similar sets of genes, produce similar lineages and are called serial homologs. However, despite of their similarities, the composition of serially homologous lineages diverges during further development in a segment-specific manner.
A focus of our recent research lies on the clarification of mechanisms, which lead to segment-specific diversification of serially homologous NB-lineages and thus to regionalization of the CNS. Lineage-divergence may occur at various stages during embryonic and postembryonic development of NBs and their progeny cells through segment-specific control of proliferation, cell fate and/or apoptosis. We are investigating the role of Hox-genes, interacting factors and target genes at different steps during segment-specific modification of neural lineages. Questions we are asking are: How is the cell- and stage-specific expression of Hox-genes and their isoforms controlled ? Which cell-specific functions do Hox-genes assume in the developing CNS ? How are their context-specific functions mediated?
Different sizes of neuroectodermal anlagen/numbers of NBs, and segment-specific shaping of serially homologous NB lineages finally lead to diversification of neural circuits along the anterior-posterior axis, which is required for proper integration of sensory input and control of locomotion and behavior. Thus, the analysis of the mechanisms underlying segmental diversification of CNS lineages may also provide a means of elucidating the relationships between development and functional units.