Allele Dmel\raps^P89

General Information
Symbol	Dmel\raps^P89	Species	D. melanogaster
Name		FlyBase ID	FBal0104444
Feature type	allele	Associated gene	Dmel\raps
Also Known As	pins^P89, pins⁸⁹

Allele class	loss of function allele
Mutagen	Delta2-3
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Nature of the Allele
Allele class	loss of function allele (Cai et al., 2003)
Mutagen	Delta2-3 (Yu et al., 2000)
Mutations Mapped to the Genome

Type Location Additional Notes References
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype	P{EP}wdb^EP3559 (Yu et al., 2000)
Nature of the lesion	Statement Reference Excision of the P{EP} element resulting in a deletion which removes part of the raps coding region. (Yu et al., 2000)
Cytology
Phenotypic Data
Phenotypic Class
	cell cycle defective (with raps^P62) (Januschke and Gonzalez, 2010) cell polarity defective (Cai et al., 2003) cell polarity defective (with raps^P62) (Januschke and Gonzalez, 2010) mitotic cell cycle defective \| embryonic stage (Yu et al., 2003) neuroanatomy defective \| embryonic stage (Yu et al., 2003) tumorigenic (with raps^P62) (Caussinus and Gonzalez, 2005)
Phenotype Manifest In
	centrosome (with raps^P62) (Rebollo et al., 2007) embryonic neuroblast & spindle (Yu et al., 2000) ganglion mother cell GMC4-2a (Yu et al., 2003) mitotic cell cycle & spindle (Yu et al., 2000) mitotic domain 9 & spindle (Yu et al., 2003, Yu et al., 2000) neuroblast (Cai et al., 2003) RP2 motor neuron (Yu et al., 2000) RP2 motor neuron \| ectopic (Yu et al., 2003, Yu et al., 2000) RP2sib neuron (Yu et al., 2003, Yu et al., 2000)
Detailed Description
	Statement Reference raps[P62]/raps[P89] mutant neuroblasts exhibit rotation of approximately 100[o] between the first and second mitoses and a further 80[o] between the second and third. Thus, altogether, the division axis of this cell rotated ~180[o] over the course of three consecutive divisions. (Januschke and Gonzalez, 2010) The first stages of centrosome movement in raps[P89]/raps[P62]/ larval neuroblasts occur as in wild type; a highly correlated behaviour is seen, as the centrosomes move in parallel toward the cortex, where they remain until one of them starts moving around the cell. However, when this movement of one centrosome starts to occur, the mutant neuroblasts show a clear difference from wild type; in the mutant neuroblasts, although migration of the centrosome is first restricted to one side of the cell, later on migration takes place throughout the entire cell, such that the trajectories of both centrosomes become fully intermingled. At this stage in the mutant neuroblasts, the cortical aster is disassembled. (Rebollo et al., 2007) The transplantation of raps^P89/raps^P62 larval neuroblast clones into the abdomen of adult hosts causes tumor growth, with clones growing to 100 times their original size thereby severely damaging and displacing the host's organs. Although genome stability is not grossly affected shortly after transplantation, 40-day-old tumors show karyotype defects such as segmental aneuploidy. Additionally, 15-20% of cells within the tumors have supernumerary centrosomes and these cells tend to be hyperploid. (Caussinus and Gonzalez, 2005) Embryos lacking both maternal and zygotic raps^P89 are antigen minus and are phenotypically indistinguishable from germline clones derived from alleles raps^P120 and raps^P17. The great majority of raps^P89 mutant neuroblasts undergo unequal divisions; however, 15% (n = 120) divide with symmetric mitotic spindles and generate equal-sized daughter cells. (Cai et al., 2003) Mitotic spindle in the neuroblast cells of mitotic domain 9 raps^P89 mutant embryos fail to reorient by 90⁰. In raps^P89 mutant embryos, markers of the basal cortical crescent are mislocalized either as randomly-placed cortical crescents or are localized throughout the cell cortex. raps^P89 mutant embryos show defects in the resolution of alternative sibling cell fate. For example, in the GMC4-2a>RP2/RP2 sib sublineage, RP2sib adopts the fate of its sibling, resulting in duplication of the eve positive RP2 neurons in 60% of the hemisegments. Moreover, a small proportion of GMC4-2a cells are mis-specified, resulting in the loss of eve-expressing RP2 neurons in 15% of hemisegments. (Yu et al., 2003) No neuronal fate changes are evident in homozygous embryos. Spindle orientation in neuroblasts and mitotic domain 9 cells is normal. Mutant embryos derived from homozygous or raps^P62/raps^P89 females (lacking maternal and zygotic raps function) have defective mitotic spindle orientation. In cells of mitotic domain 9, the 90^o reorientation which normally occurs in wild-type embryos (which results in the orientation of the spindle along the apical/basal axis) fails to occur. Mitotic spindles of neuroblasts in the segmented central nervous system also often fail to adopt an apical/basal orientation. In approximately 60% of hemisegments, duplicated RP2 neurons are found at the expense of the RP2sib neuron. These two RP2 neurons appear to have indistinguishable nuclear size. In approximately 15% of hemisegments no eve-expressing RP2/RP2sib neurons are produced due to a failure to correctly specify the GMC progenitor of these neurons. (Yu et al., 2000)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement Reference raps^P89 has cell polarity defective phenotype, enhanceable by aPKC^dsRNA.cCa (Cai et al., 2003) raps^P89 has cell polarity defective phenotype, enhanceable by baz^dsRNA.cCa (Cai et al., 2003)
Suppressed by
Statement Reference raps^P89 has mitotic cell cycle defective \| embryonic stage phenotype, suppressible by Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has neuroanatomy defective \| embryonic stage phenotype, suppressible by Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} (Yu et al., 2003)
NOT suppressed by
Statement Reference raps^P89 has neuroanatomy defective \| embryonic stage phenotype, non-suppressible by Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has neuroanatomy defective \| embryonic stage phenotype, non-suppressible by Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} (Yu et al., 2003)
Suppressor of
Statement Reference raps[+]/raps^P89 is a suppressor \| partially of cell polarity defective phenotype of Gαi^Scer\UAS.cCa, Scer\GAL4^sca-P309 (Cai et al., 2003) raps^P89 is a suppressor \| maternal effect \| partially of cell polarity defective phenotype of Gαi^Scer\UAS.cCa, Scer\GAL4^sca-P309 (Cai et al., 2003)
Phenotype Manifest In
Enhanced by
Statement Reference raps^P89 has neuroblast phenotype, enhanceable by aPKC^dsRNA.cCa (Cai et al., 2003) raps^P89 has neuroblast phenotype, enhanceable by baz^dsRNA.cCa (Cai et al., 2003)
Suppressed by
Statement Reference raps^P89 has RP2 motor neuron \| ectopic phenotype, suppressible \| partially by Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has RP2sib neuron phenotype, suppressible \| partially by Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} (Yu et al., 2003)
NOT suppressed by
Statement Reference raps^P89 has mitotic domain 9 & spindle phenotype, non-suppressible by Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has mitotic domain 9 & spindle phenotype, non-suppressible by Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has RP2 motor neuron \| ectopic phenotype, non-suppressible by Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has RP2 motor neuron \| ectopic phenotype, non-suppressible by Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has RP2sib neuron phenotype, non-suppressible by Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} (Yu et al., 2003) raps^P89 has RP2sib neuron phenotype, non-suppressible by Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} (Yu et al., 2003)
Suppressor of
Statement Reference raps[+]/raps^P89 is a suppressor \| partially of neuroblast phenotype of Gαi^Scer\UAS.cCa, Scer\GAL4^sca-P309 (Cai et al., 2003) raps^P89 is a suppressor \| maternal effect \| partially of neuroblast phenotype of Gαi^Scer\UAS.cCa, Scer\GAL4^sca-P309 (Cai et al., 2003)
Other
Statement Reference baz^dsRNA.cFa, raps^P89 has neuroblast phenotype (Fuse et al., 2003, Fuse et al., 2003)
Additional Comments
Genetic Interactions
Statement Reference High frequencies (100%, n = 50) of equal size neuroblast divisions are observed in baz^dsRNA.cCa; raps^P89 mutant embryos. In these equal size divisions both spindle asymmetry and spindle displacement fail to occur. High frequencies of equal size neuroblast divisions occur in raps^P89, aPKC^dsRNA.cCa (80%, n = 46) mutants. In these equal size divisions both spindle asymmetry and spindle displacement fail to occur. The cleavage furrow is equidistant to the centrosomes and both centrosomes lie close to the cortex. A low level of symmetric neuroblast divisions occur in embryos maternally and zygotically homozygous for raps^P89, expressing G-iα65A^Scer\UAS.cCa driven by Scer\GAL4^sca-P309. The number of asymmetric divisions is dramatically higher in otherwise genetically identical embryos, zygotically heterozygous for raps^P89. The frequency of equal size neuroblast division in G-iα65A^dsRNA.cCa embryos is slightly increased by homozygosity for raps^P89 (26%, n = 34). (Cai et al., 2003) When baz^dsRNA.cFa is added to raps^P89 mutants neuroblasts form a small symmetric spindle at metaphase, both halves similar to the basal half of the wild-type spindle. (Fuse et al., 2003)
Xenogenetic Interactions
Statement Reference Ectopic expressed Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} is able to restore 90^o spindle rotation in raps^P89 embryonic neuroblast cells of mitotic domain 9. In contrast, neither Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} or Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} can restore this spindle rotation. The introduction of Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} into raps^P89 mutant embryos allows basal proteins to localize as in wild-type cells. Ectopic expression of Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} in raps^P89 mutant embryos recues defects in the resolution of alternative neuron sibling cell fate. For example, transformation of RP2 sib neurons to RP2 neurons is largely suppressed. Neither Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} or Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} are able to mediate this rescue.Ectopic expressed Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} is able to restore 90^o spindle rotation in raps^P89 embryonic neuroblast cells of mitotic domain 9. In contrast, neither Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} or Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} can restore this spindle rotation. The introduction of Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} into raps^P89 mutant embryos allows basal proteins to localize as in wild-type cells. Ectopic expression of Mmus\Gpsm2^{hs.2xT:Zzzz\FLAG} in raps^P89 mutant embryos recues defects in the resolution of alternative neuron sibling cell fate. For example, transformation of RP2 sib neurons to RP2 neurons is largely suppressed. Neither Mmus\Gpsm2^{1-369.hs.2xT:Zzzz\FLAG} or Mmus\Gpsm2^{366-672.hs.2xT:Zzzz\FLAG} are able to mediate this rescue. (Yu et al., 2003)
Complementation & Rescue Data
Rescued by	raps^P89 is rescued by raps^Scer\UAS.cYa/Scer\GAL4^sca-P309 (Yu et al., 2000)
Comments
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 4 )
Reported As
Symbol Synonym	pins⁸⁹ (Yu et al., 2003, Yu et al., 2003, Cai et al., 2003, Wang et al., 2006) pins^P89 (Yu et al., 2005, Yu et al., 2000, Rebollo et al., 2007, Januschke and Gonzalez, 2010, Janic et al., 2010) pins P89 (Fuse et al., 2003) raps^P89 (Caussinus and Gonzalez, 2005)
Name Synonym
Secondary FlyBase IDs

References ( 11 )
Research paper	Janic et al., 2010, Science 330(6012): 1824--1827 Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. [FBrf0212713] Januschke and Gonzalez, 2010, J. Cell Biol. 188(5): 693--706 The interphase microtubule aster is a determinant of asymmetric division orientation in Drosophila neuroblasts. [FBrf0210175] Rebollo et al., 2007, Dev. Cell 12(3): 467--474 Functionally Unequal Centrosomes Drive Spindle Orientation in Asymmetrically Dividing Drosophila Neural Stem Cells. [FBrf0194965] Wang et al., 2006, EMBO J. 25(24): 5783--5793 Drosophila homologs of mammalian TNF/TNFR-related molecules regulate segregation of Miranda/Prospero in neuroblasts. [FBrf0192517] Caussinus and Gonzalez, 2005, Nat. Genet. 37(10): 1125--1129 Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. [FBrf0188152] Yu et al., 2005, Genes Dev. 19(11): 1341--1353 Locomotion defects, together with Pins, regulates heterotrimeric G-protein signaling during Drosophila neuroblast asymmetric divisions. [FBrf0187602] Cai et al., 2003, Cell 112(1): 51--62 Apical complex genes control mitotic spindle geometry and relative size of daughter cells in Drosophila neuroblast and pI asymmetric divisions. [FBrf0155600] Fuse et al., 2003, Curr. Biol. 13(11): 947--954 Heterotrimeric g proteins regulate daughter cell size asymmetry in Drosophila neuroblast divisions. [FBrf0159715] Yu et al., 2003, J. Cell Biol. 162(4): 623--633 Distinct roles of Galphai and Gbeta13F subunits of the heterotrimeric G protein complex in the mediation of Drosophila neuroblast asymmetric divisions. [FBrf0162191] Yu et al., 2003, J. Cell Sci. 116(5): 887--896 A mouse homologue of Drosophila pins can asymmetrically localize and substitute for pins function in Drosophila neuroblasts. [FBrf0155873] Yu et al., 2000, Cell 100(4): 399--409 Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. [FBrf0125333]

Allele Dmel\rapsP89

Allele Dmel\raps^P89