The differentiation of the serotonin neurons in the Drosophila ventral nerve cord depends on the function of the zink finger protein Eagle

Institut für Genetik, Zellbiologie, Universität Mainz, Saarstraße 21, 55122 Mainz,

The larval central nervous system of Drosophila is generated from a segmentally repeated set of neural precursors, the neuroblasts (NBs). Each NB has a unique identity and produces a specific cell lineage. To elucidate how the complex pattern of different cell types within a functional cns is accomplished it is necessary to understand the principles according to which CNS lineages are generated. We use the lineage of NB 7-3 as a model system. Single cell labelings reveal a small number of progeny for NB 7-3 comprising three contralaterally projecting interneurons and one motoneuron. In the abdominal neuromeres two of these interneurons produce the neurotransmitter serotonin. At late embryonic stages these are the only cells expressing huckebein (hkb) and engrailed (en) simultaniously, leading to the hypothesis that these genes act in combination to determine the serotoninergic cell fate. In support to this, loss of function mutations in these genes lead to loss of serotonin immunoreactivity (Lundell et al., 1996). , a recently cloned gene (Higashijima et al., 1996) coding for a knirps-like zink finger transcription factor, is expressed in NB 7-3 just after delamination. The gene product is present in all it's progeny and fades away after stage 17. Analysis of loss of function mutations in eagle revealed a nearly complete loss of serotonin immunoreactivity, loss of en expression in at least one of these cells and pathfinding defects. Ectopic expression of eagle leads to 1-2 additional serotoninergic neurons per hemineuromere. This shows that eagle is important for the normal development of the NB 7-3 lineage and is competent to induce serotoninergic differentiation. Loss of function mutations in engrailed lead in 90% of mutant hemineuromeres to a complete loss of eg staining at the position of the NB 7-3 neurons. This suggests, that en acts "upstream" of eg and is, most likely, not directly involved in establishing the serotoninergic fate. In contrast to this, wildtype eagle expression is observed in all NB 7-3 progenies in about 80% of hkb² hemineuromeres (hkb² is a strong hypomorphic allele of huckebein, Weigel et. al. 1990). Furthermore huckebein expression in NB 7-3 is wildtype in the mutant eagle background. Therefore hkb seems to act parallel with eagle in establishing the serotoninergic fate in the NB 7-3 lineage.

Supported by the DFG (TE 130/4-3)

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