Abstract
The bipotential Ganglion Mother Cells, or GMCs, in the Drosophila CNS asymmetrically divide to generate two distinct post-mitotic neurons. Here, we show that the midline repellent Slit (Sli), via its receptor Roundabout (Robo), promotes the terminal asymmetric division of GMCs. In GMC-1 of the RP2/sib lineage, Slit promotes asymmetric division by down regulating two POU proteins, Nubbin and Mitimere. The down regulation of these proteins allows the asymmetric localization of Inscuteable, leading to the asymmetric division of GMC-1. Consistent with this, over-expression of these POU genes in a late GMC-1 causes mis-localization of Insc and symmetric division of GMC-1 to generate two RP2s. Similarly, increasing the dosage of the two POU genes in sli mutant background enhances the penetrance of the RP2 lineage defects whereas reducing the dosage of the two genes reduces the penetrance of the phenotype. These results tie a cell-non-autonomous signaling pathway to the asymmetric division of precursor cells during neurogenesis.
Highlights
In both insects and vertebrates, midline cells play a key role in the formation of the axon commissures that interconnect the left and the right sides of the developing CNS (Crews et al, 1988; Thomas et al, 1988; Nambu et al, 1990; Nambu et al, 1991; Klambt et al, 1991)
Our results indicate that the disruption of the asymmetric localization of Insc by loss of sli in at least ganglion mother cells (GMCs)-1 of the RP2/sib lineage is due to the up-regulation of the two POU proteins, Nubbin (Nub; known as Pdm1) and Mitimere (Miti; known as Pdm2)
To determine the requirement for Sli signaling in precursor cell division, we focussed on two GMC lineages in the ventral nerve cord of the Drosophila embryo: the GMC-1→RP/sib lineage generated by NB4-2 and the GMC1-1a→aCC/pCC lineage, generated by NB1-1 (Thomas et al, 1984)
Summary
In both insects and vertebrates, midline cells play a key role in the formation of the axon commissures that interconnect the left and the right sides of the developing CNS (Crews et al, 1988; Thomas et al, 1988; Nambu et al, 1990; Nambu et al, 1991; Klambt et al, 1991). Efforts have been directed to elucidating axon repulsion mediated by the Slit (Sli)-Roundabout (Robo) signaling pathway (Rothberg et al, 1990; Kidd et al, 1999; Brose et al, 1999; Li et al, 1999; Wang et al, 1999; BaCharvet et al, 1999; Simpson et al, 2000; Rajagopalan et al, 2000) These studies reveal that growth cones that express Robo, a cell surface receptor, will not enter and cross the midline where the Sli ligand is expressed at high levels owing to a repellent Sli-Robo interaction. There have been several studies that reveal the repellent action of Sli-Robo in axon guidance, whether or not Sli signaling is required for neuronal lineage elaboration has never been addressed
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