Polycomb group (PcG) and trithorax group (trxG) proteins are well known for their role in the maintenance of silent and active expression states of homeotic genes. However, PcG proteins may also be required for the control of cellular proliferation in vertebrates. In Drosophila, PcG factors act by associating with specific DNA regions termed PcG response elements (PREs). Here, we have investigated whether Drosophila cell cycle genes are directly regulated by PcG proteins through PREs. We have isolated a PRE that regulates Cyclin A (CycA) expression. This sequence is bound by the Polycomb (PC) and Polyhomeotic (PH) proteins of the PcG, and also by GAGA factor (GAF), a trxG protein that is usually found associated with PREs. This sequence In Drosophila, PcG-mediated repression occurs through cis-regulatory DNA sequences termed PREs (PcG response elements) (Zink et al. 1991;Simon et al. 1993). PREs share several tractable molecular and genetic properties: (1) PcG proteins bind directly to PREs (Zink and Paro 1995; Strutt and Paro 1997); (2) in vivo, PREs induce repression of the adjacent white reporter gene, producing a variegated phenotype (Fauvarque and Dura 1993); (3) this variegated phenotype is dependent on PcG and trxG proteins; and (4) PREs induce pairingsensitive repression (PSR) (for review, see Kassis 2002).Epigenetic regulation of gene expression is emerging as a key mechanism in the control of cellular proliferation. In vertebrates, PRC1 and PRC2/3 components have been implicated in the regulation of proliferation, acting as either potent activators or repressors of the cell cycle. Progression through the cell cycle depends primarily on the activity of the cyclin-dependent kinases (Cdks). Cdks, upon association with their respective cyclin partners, mediate the transitions between the different cell cycle phases. Although with increased complexity, cell Cold Spring Harbor Laboratory Press on May 12, 2018 -Published by genesdev.cshlp.org Downloaded from
One challenging question in neurogenesis concerns the identification of cues that trigger axonal growth and pathfinding to form stereotypic neuronal networks during the construction of a nervous system. Here, we show that in Drosophila, Engrailed (EN) and Gooseberry-Neuro (GsbN) act together as cofactors to build the posterior commissures (PCs), which shapes the ventral nerve cord. Indeed, we show that these two proteins are acting together in axon growth and midline crossing, and that this concerted action occurs at early development, in neuroblasts. More precisely, we identified that their expressions in NB 6-4 are necessary and sufficient to trigger the formation of the PCs, demonstrating that segmentation genes such as EN and GsbN play a crucial role in the determination of NB 6-4 in a way that will later influence growth and guidance of all the axons that form the PCs. We also demonstrate a more specific function of GsbN in differentiated neurons, leading to fasciculations between axons, which might be required to obtain PC mature axon bundles.
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