Disease relevance of pros

• In brat or prospero mutants, both daughter cells grow and behave like neuroblasts leading to the formation of larval brain tumors [1].
• In the ganglion mother cell, svp is repressed by Prospero, a transcription factor asymmetrically localised to this cell during mitosis [2].

Psychiatry related information on pros

• The position of such QTL (approximately 84A-88B) with effects on courtship and copulation aspects of mating includes the candidate sex determination gene doublesex (84E5-6) and Voila (86E1-2), a gene that affects male courtship in D. melanogaster [3].

High impact information on pros

• Like Prospero, Brat binds and cosegregates with the adaptor protein Miranda [1].
• Similar defects are seen in lethal giant larvae (lgl) mutants where Brat and Prospero are not asymmetric [1].
• While Prospero regulates cell-cycle gene transcription, Brat acts as a posttranscriptional inhibitor of dMyc [1].
• A direct link is established between DER activation of a transcription enhancer in prospero and binding of two transcription factors that are targets of DER signaling [4].
• We show that Sevenless activates prospero independent of the enhancer and involves targeted degradation of Tramtrack, a transcription repressor [4].

Biological context of pros

• Inscuteable and Staufen mediate asymmetric localization and segregation of prospero RNA during Drosophila neuroblast cell divisions [5].
• Inscuteable and Staufen interact and colocalize with prospero RNA on the apical cortex of interphase neuroblasts [5].
• Neuroblasts in the developing Drosophila CNS asymmetrically localize the cell fate determinants Numb and Prospero as well as prospero RNA to the basal cortex during mitosis [6].
• The Mira/Pros telophase rescue seen in inscuteable mutant NBs requires DTRAF1 [7].
• Interestingly, prospero mRNA is similarly segregated by the dsRNA binding protein, Staufen [8].

Anatomical context of pros

• When neuroblasts divide, inscuteable acts to coordinate protein localization and mitotic spindle orientation, ensuring that asymmetrically localized determinants like Prospero partition into one progeny. staufen encodes a dsRNA-binding protein implicated in mRNA transport in oocytes [5].
• Miranda protein is localized asymmetrically, along with Prospero, to the basal cell membrane during mitosis [9].
• During growth cone guidance, Prospero positively regulates cycE promoting cell proliferation [10].
• Furthermore, we showed that outside the NB6-4T lineage most glial cells appeared independently of Pros [11].
• Drosophila neuroblasts and epithelial cells in the procephalic neurogenic region divide perpendicular to the surface, and segregate the proteins Numb and Prospero into the basal daughter cell [12].

Associations of pros with chemical compounds

• Our data suggest that DTRAF1 binds to Baz and acts downstream of Egr in the Mira/Pros telophase rescue pathway [7].
• This compensatory mechanism has been referred to as 'telophase rescue'. We demonstrate that the Drosophila homolog of the mammalian tumor-necrosis factor (TNF) receptor-associated factor (DTRAF1) and Eiger (Egr), the homolog of the mammalian TNF, are required for telophase rescue of Mira/Pros [7].
• Regulated transcription of the prospero gene in the Drosophila eye provides a model for how gene expression is specifically controlled by signals from receptor tyrosine kinases [4].
• Nuclear export of Prospero, which is sensitive to the drug leptomycin B, is mediated by Exportin [13].

Physical interactions of pros

• Staufen binds prospero RNA in its 3'UTR [5].
• Our results suggest that miranda functions downstream of inscuteable and works as an adapter that connects Prospero to the basal cell membrane during asymmetric cell division [9].

Enzymatic interactions of pros

• Hyperstable Yan (ACT) cannot be phosphorylated and blocks prospero expression [14].

Regulatory relationships of pros

• In Drosophila neuroblasts, inscuteable controls both spindle orientation and the asymmetric localization of the cell-fate determinants Prospero and Numb [15].
• Furthermore, the maintenance of hb expression in the GMC is regulated by the activity of Prospero (Pros), a transcription factor which asymmetrically segregates into the GMC during mitosis and inhibits Svp activity on both, the transcriptional and posttranscriptional level [16].
• Neuronal Vein activates the MAPKinase signalling pathway in the glia with highest Prospero levels, coupling axon extension with glial proliferation [10].
• The expression of Pros in the normal PIIb cell appears to be regulated by Notch signaling [17].
• Dendrite development is altered in prospero mutants and in transgenic embryos expressing a constitutively active form of the small GTPase cdc42 [18].

Other interactions of pros

• Thus, the differential regulation of hb between the neuroblasts and the ganglion mother cells is achieved by a mechanism that integrates information created by the asymmetric distribution of a cell-fate determinant upon mitosis (Prospero) and a transcriptional repressor present in both cells (Seven-up) [2].
• In this study, we show that Miranda is colocalized with Staufen and Prospero in neuroblasts, and is required for the asymmetric cortical localization of both proteins [19].
• Simultaneous expression of inscuteable and string in the snail family deletion mutant efficiently restores Prospero expression in ganglion mother cells, demonstrating that the two genes are key targets of Snail in neuroblasts [20].
• First, we found that prospero (pros) mutations led to a loss of expression of Glial cells missing, which is essential to trigger glial differentiation, in the NB6-4T lineage [11].
• However, from stage 15 of embryogenesis, expression of locomotion defects (loco) and prospero (pros) was found to be missing in a subset of LG [21].

Analytical, diagnostic and therapeutic context of pros

• Developmental 2D Western blots, cell fractionation assays, and analysis of a missense prospero mutation show that cortical Prospero protein is highly phosphorylated compared to nuclear Prospero protein [22].

References