Slit signaling promotes the terminal asymmetric division of neural precursor cells in the Drosophila CNS.
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.
Mehta
B
B
Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Bhat
K M
KM
D000818:Animals; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002490:Central Nervous System / Q000196:embryology*; D015536:Down-Regulation; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D018398:Homeodomain Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D050809:POU Domain Factors; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors; D000097905:Roundabout Proteins
D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D050809:POU Domain Factors; D011971:Receptors, Immunologic; D014157:Transcription Factors; D000097905:Roundabout Proteins; C104121:nub protein, Drosophila; C072851:pdm2 protein, Drosophila; C066819:sli protein, Drosophila