Expression of Mammalian BM88/CEND1 in Drosophila Affects Nervous System Development by Interfering with Precursor Cell Formation
1 Department of Clinical Biochemistry, Aghia Sophia Children’s Hospital, 11527 Athens, Greece
2 Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, 11521 Athens, Greece
3 ‘‘Alexander Fleming’’ Biomedical Sciences Research Centre, 16672 Athens, Greece
Abstract
We used Drosophila melanogaster as an experimental model to express mouse and pig BM88/CEND1 (cell cycle exit and neuronal differentiation 1) in order to investigate its potential functional effects on Drosophila neurogenesis. BM88/CEND1 is a neuron-specific protein whose function is implicated in triggering cells to exit from the cell cycle and differentiate towards a neuronal phenotype. Transgenic flies expressing either mouse or pig BM88/CEND1 in the nervous system had severe neuronal phenotypes with variable expressivity at various stages of embryonic development. In early embryonic stage 10, BM88/CEND1 expression led to an increase in the neural-specific antigenicity of neuroectoderm at the expense of precursor cells [neuroblasts (Nbs) and ganglion mother cells (GMCs)] including the defective formation and differentiation of the MP2 precursors, whereas at later stages (12–15), protein accumulation induced gross morphological defects primarily in the CNS accompanied by a reduction of Nb and GMC markers. Furthermore, the neuronal precursor cells of embryos expressing BM88/CEND1 failed to carry out proper cell-cycle progression as revealed by the disorganized expression patterns of specific cell-cycle markers. BM88/CEND1 accumulation in the Drosophila eye affected normal eye disc development by disrupting the ommatidia. Finally, we demonstrated that expression of BM88/CEND1 modified/reduced the levels of activated MAP kinase indicating a functional effect of BM88/CEND1 on the MAPK signaling pathway. Our findings suggest that the expression of mammalian BM88/CEND1 in Drosophila exerts specific functional effects associated with neuronal precursor cell formation during embryonic neurogenesis and proper eye disc development. This study also validates the use of Drosophilaas a powerful model system in which to investigate gene function and the underlying molecular mechanisms.
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