scholarly journals Slit signaling promotes the terminal asymmetric division of neural precursor cells in the Drosophila CNS

Development ◽  
2001 ◽  
Vol 128 (16) ◽  
pp. 3161-3168 ◽  
Author(s):  
Brijesh Mehta ◽  
Krishna Moorthi Bhat

The bipotential Ganglion Mother Cells, or GMCs, in the DrosophilaCNS 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 insli 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.


2015 ◽  
Vol 1625 ◽  
pp. 275-286 ◽  
Author(s):  
Xin Chen ◽  
Wei Wang ◽  
Jianfang Zhang ◽  
Shiyong Li ◽  
Yilin Zhao ◽  
...  




2011 ◽  
Vol 286 (12) ◽  
pp. 10593-10604 ◽  
Author(s):  
Marta Fumagalli ◽  
Simona Daniele ◽  
Davide Lecca ◽  
Philip R. Lee ◽  
Chiara Parravicini ◽  
...  

The developing and mature central nervous system contains neural precursor cells expressing the proteoglycan NG2. Some of these cells continuously differentiate to myelin-forming oligodendrocytes; knowledge of the destiny of NG2+ precursors would benefit from the characterization of new key functional players. In this respect, the G protein-coupled membrane receptor GPR17 has recently emerged as a new timer of oligodendrogliogenesis. Here, we used purified oligodendrocyte precursor cells (OPCs) to fully define the immunophenotype of the GPR17-expressing cells during OPC differentiation, unveil its native signaling pathway, and assess the functional consequences of GPR17 activation by its putative endogenous ligands, uracil nucleotides and cysteinyl leukotrienes (cysLTs). GPR17 presence was restricted to very early differentiation stages and completely segregated from that of mature myelin. Specifically, GPR17 decorated two subsets of slowly proliferating NG2+ OPCs: (i) morphologically immature cells expressing other early proteins like Olig2 and PDGF receptor-α, and (ii) ramified preoligodendrocytes already expressing more mature factors, like O4 and O1. Thus, GPR17 is a new marker of these transition stages. In OPCs, GPR17 activation by either uracil nucleotides or cysLTs resulted in potent inhibition of intracellular cAMP formation. This effect was counteracted by GPR17 antagonists and receptor silencing with siRNAs. Finally, uracil nucleotides promoted and GPR17 inhibition, by either antagonists or siRNAs, impaired the normal program of OPC differentiation. These data have implications for the in vivo behavior of NG2+ OPCs and point to uracil nucleotides and cysLTs as main extrinsic local regulators of these cells under physiological conditions and during myelin repair.



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