Miranda directs Prospero to a daughter cell during Drosophila asymmetric divisions

Abstract

Asymmetric cell division is a general process used in many developmental contexts to create two differently fated cells from a single progenitor cell. Intrinsic mechanisms like the asymmetric transmission of cell-fate determinants during cell division, and extrinsic cell-interaction mechanisms, can mediate asymmetric divisions. During embryonic development of the Drosophila central nervous system, neural stem cells called neuroblasts divide asymmetrically to produce another multipotent neuroblast and a ganglion mother cell (GMC) of more restricted developmental potential. Intrinsic mechanisms promote asymmetric division of neuroblasts: for example, the transcription factor Prospero localizes to the basal cell cortex of mitotic neuroblasts and then segregates exclusively into the GMC, which buds off from the basal side of the neuroblast. In the GMC, Prospero translocates to the nucleus, where it establishes differential gene expression between sibling cells. Here we report the identification of a gene, miranda, which encodes a new protein that co-localizes with Prospero in mitotic neuroblasts, tethers Prospero to the basal cortex of mitotic neuroblasts, directing Prospero into the GMC, and releases Prospero from the cell cortex within GMCs. miranda thus creates intrinsic differences between sibling cells by mediating the asymmetric segregation of a transcription factor into only one daughter cell during neural stem-cell division.

Regulation of Glia Number in Drosophila by Rap/Fzr, an Activator of the Anaphase-Promoting Complex, and Loco, an RGS Protein

“…Our results showed that, in the larval brain, Loco is colocalized with Miranda and Rap/Fzr in the basal axis, whereas during asymmetric division of embryonic neuroblasts, Loco is expressed in the apical axis (Yu et al 2005). Although Miranda is a known mediator of asymmetric division of embryonic neuroblasts and a specific marker for larval neuroblasts, its function in postembryonic development has not been completely elucidated (Ikeshima-Kataoka et al 1997;Shen et al 1998;Slack et al 2006). Colocalization of Loco with Miranda and Rap/Fzr (Figure 7) suggests a possible functional role for these molecules during postembryonic neuroblast division.…”

Insights into neural stem cell biology from flies

“…Asymmetric segregation of Pros protein and pros RNA is mediated by the adaptor protein Miranda (Mira). Once segregated to the GMC, Mira is degraded, thereby releasing Pros from the cortex (Ikeshima-Kataoka et al 1997;Shen et al 1997;Matsuzaki et al 1998). Pros can then enter the nucleus, where it has been thought to specify GMC identity by promoting the expression of GMC-specific genes and repressing the expression of neuroblast-specific genes (but see Choksi et al 2006).…”

Scribble protein domain mapping reveals a multistep localization mechanism and domains necessary for establishing cortical polarity

“…the coiled-coil Miranda (Mira) protein, the transcription factor Prospero (Pros), the RNA-binding protein Staufen, and its cargo pros mRNA form one complex (Hirata et al, 1995;Ikeshima-Kataoka et al, 1997;Knoblich et al, 1995;Shen et al, 1997;Spana and Doe, 1995) and Partner of numb (Pon) and Numb form another complex (Lu et al, 1998;Rhyu et al, 1994). Formation of the apical cortical domain is necessary for proper basal targeting; loss of Par3-Par6-aPKC components results in a uniform cortical distribution of Pros and Mira at metaphase (Petronczki and Knoblich, 2001;Schober et al, 1999;Rolls et al, 2003;Wodarz et al, 1999).…”