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Allele Dmel\scrib^unspecified

General Information
Symbol	Dmel\scribunspecified	Species	D. melanogaster
Name		FlyBase ID	FBal0103571
Feature type	allele	Associated gene	Dmel\scrib
Allele class
Mutagen
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.
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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
Mutagen
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
Nature of the lesion	Statement Reference
Cytology
Phenotypic Data
Phenotypic Class
	cell polarity defective | somatic clone (Lu and Bilder, 2005) increased cell death | larval stage | somatic clone (Uhlirova et al., 2005) neuroanatomy defective | somatic clone (Uhlirova et al., 2005) tumorigenic | larval stage | somatic clone (Uhlirova et al., 2005)
Phenotype Manifest In
	embryonic/first instar larval cuticle (Bilder and Perrimon, 2000) embryonic/larval fat body (Wu et al., 2001) epithelial cell | embryonic stage (Bilder and Perrimon, 2000) eye | somatic clone (Uhlirova et al., 2005) eye-antennal disc | somatic clone (Uhlirova et al., 2005) follicle cell | cell autonomous | somatic clone (Bilder et al., 2000) imaginal disc (Bilder et al., 2000)
Detailed Description
	Statement Reference Homozygous scribunspecified mutant clones in the larval eye imaginal discs form benign lesions in the adult eye. Clonal areas in such eyes appear undifferentiated and disorganised. Neuronal differentiation is severely impaired in scribunspecified mutant clones. Homozygous scribunspecified mutant clones in the eye imaginal disc grow into sizable clones of disorganised appearance and do not express neuronal markers, indicating their failure to differentiate. Homozygous scribunspecified mutant clones contribute only 12.4% of the eye-antennal imaginal disc, while wild-type clones of the same size contribute 41.2%. Consistently, the number of apoptotic cells in the clonal fraction is significantly increased (16.6% in the mutant compared to 2% in wild-type). (Uhlirova et al., 2005) The cells in the larval fat body are more rounded than normal. (Wu et al., 2001) Embryos that are maternally and zygotically mutant for scrib produce a corrugated cuticular surface that is riddled with holes. The embryos proceed normally through precellular development and the epithelial blastoderm forms as in wild type. After gastrulation however, the organisation of the ectodermal epithelium is disrupted as cells lose their columnar shape and planar arrangement. These defects become progressively more severe as development proceeds. The epidermis of late embryos is frequently interrupted and consists of groups of irregular rounded cells that are separating from one another. Most of the epidermis is organised into multilayered strips or tubes of cells that have lost contact with the underlying tissue. (Bilder and Perrimon, 2000) Clones of follicle cells homozygous for scribunspecified become round and multilayered with polarity defects (in contrast to the regular monolayered follicle epithelium seen in wild type). These epithelial defects are cell autonomous. Most homozygotes hatch and survive into late larval stages. (Bilder et al., 2000)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement Reference scribunspecified has lethal | recessive phenotype, enhanceable by dlg1[+]/dlg1unspecified (Bilder et al., 2000)
Enhancer of
Statement Reference scribunspecified/scribunspecified is an enhancer | somatic clone of tumorigenic | somatic clone phenotype of Ras85DV12.Scer\UAS, Scer\GAL4Act5C.PI/Scer\GAL4Act5C.PI (Pagliarini and Xu, 2003, Pagliarini and Xu, 2003)
Phenotype Manifest In
Enhanced by
Statement Reference scribunspecified has imaginal disc phenotype, enhanceable by l(2)gl[+]/l(2)glunspecified (Bilder et al., 2000)
Other
Statement Reference dlg1[+]/dlg1unspecified, scribunspecified has dorsal closure embryo phenotype (Bilder et al., 2000) dlg1unspecified, scribunspecified has dorsal closure embryo phenotype (Bilder et al., 2000) l(2)glunspecified, scribunspecified has embryonic/first instar larval cuticle phenotype (Bilder et al., 2000, Bilder et al., 2000) Ras85DV12.Scer\UAS, Scer\GAL4Act5C.PI/Scer\GAL4Act5C.PI, scribunspecified has basal lamina & eye disc | somatic clone phenotype (Pagliarini and Xu, 2003, Pagliarini and Xu, 2003)
Additional Comments
Genetic Interactions
Statement Reference Expression of hepAct.Scer\UAS in scribunspecified mutant clones under the control of Scer\GAL4Act5C.PI suppressed the scribunspecified phenotype to revert to an essentially wild-type appearance, without the marked lesions resulting from scrib-deficient tissue. Significantly, these phenotypically rescued eyes do not contain any clonal cells, suggesting that JNK activity (increased by expression of hep) counteracts the outgrowth of scribunspecified tissue or causes the removal of the mutant cells. These eyes are the same size as wild-type. Downregulation of JNK signaling in clones of scribunspecified mutant tissue by overexpression of bskK53R.Scer\UAS suppresses apoptosis (from 16.6% to wild-type levels of 25%) and increases the overgrowth of the tissue, even compared to wild-type, resulting in scribunspecified bskK53R.Scer\UAS clones contributing over 70% of the tissue in third instar eye imaginal discs. Clones of eye imaginal discs that express phlScer\UAS.F179 autonomously (under the control of Scer\GAL4Act5C.PI) in scribunspecified clones grow into massive and invasive tumours during larval stages, resulting in 80% of animals not pupating and dying as giant larvae. Expression of hepAct.Scer\UAS in eye imaginal disc clones that express phlScer\UAS.F179 (under the control of Scer\GAL4Act5C.PI) and scribunspecified results in adult eyes with massive overgrowth. The heads are significantly bigger and the retina of these mutants are dramatically larger than that of a wild-type eye. In many cases, the retina is folded and bunched to accommodate the surfeit of tissue. These severely hyperplastic eye structures are well patterned and show a distinctive ommatidial organisation. The tumourous overgrowth is induced non-autonomously in the wild-type cells surrounding the hepAct.Scer\UAS phlScer\UAS.F179 (both under the control of Scer\GAL4Act5C.PI) scribunspecified cells. (Uhlirova et al., 2005) Marked clones in the eye disc expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI and which are also homozygous for scribunspecified show metastatic behaviour; third instar larvae carrying these marked clones have large primary tumours in the head and also have small groups of cells floating in the hemolymph and other distant sites. The majority of ectopic tumour cells spread from the primary tumour onto the ventral nerve cord (VNC), eventually enveloping it and also spread into the first and second leg discs and tracheal vasculature at a lower frequency. The mutant cells can invade the inside of the VNC and the leading edge of the cells has a morphology common to actively migrating cells. The basement membrane has many points of discontinuity in eye discs containing clones which are homozygous for scribunspecified and which are expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI, and mutant cells spread from these areas. The metastatic behaviour seen in marked clones in the eye disc which are homozygous for scribunspecified and are also expressing Ras85DV12.Scer\UAS under the control of Scer\GAL4Act5C.PI is suppressed if they are co-expressing scribScer\UAS.cBa. (Pagliarini and Xu, 2003) Homozygous embryos that are also heterozygous for dlg1unspecified die before hatching, with defects evident in dorsal closure. Embryos lacking zygotic scrib and l(2)gl function die exhibiting phenotypes that are similar to the absence of maternal and zygotic scrib or l(2)gl function. The imaginal disc phenotype of scribunspecified hypomorphic larvae is enhanced by heterozygosity for l(2)glunspecified. (Bilder et al., 2000)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Rescued by	scribunspecified is rescued by scribhs.PB (Bilder and Perrimon, 2000)
Comments
Stocks ( 0 )
Notes on Origin
Discoverer
External Crossreferences & Linkouts
Other Crossreferences
Linkouts
Synonyms & Secondary IDs ( 1 )
Reported As
Symbol Synonym	scribunspecified
Name Synonym
Secondary FlyBase IDs
References ( 7 )
Research paper	Lu and Bilder, 2005, Nat. Cell Biol. 7(12): 1232--1239 Endocytic control of epithelial polarity and proliferation in Drosophila. [FBrf0191263] Uhlirova et al., 2005, Proc. Natl. Acad. Sci. U.S.A. 102(37): 13123--13128 Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model. [FBrf0188278] Pagliarini and Xu, 2003, Science 302(5648): 1227--1231 A genetic screen in Drosophila for metastatic behavior. [FBrf0168030] Wu et al., 2001, Genetics 159(1): 189--199 Drosophila immunity. Genes on the third chromosome required for the response to bacterial infection. [FBrf0138410] Bilder et al., 2000, Science 289(5476): 113--116 Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. [FBrf0128403] Bilder and Perrimon, 2000, Nature 403(6770): 676--680 Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. [FBrf0125422]
Supplementary material	Luschnig et al., 2004, Genetics 167(1): Supplemental Table One. [FBrf0179048]