Allele Dmel\brat¹¹

General Information
Symbol	Dmel\brat¹¹	Species	D. melanogaster
Name		FlyBase ID	FBal0001236
Feature type	allele	Associated gene	Dmel\brat

Map ( GBrowse )
Allele class
Mutagen	ethyl methanesulfonate, formaldehyde
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	ethyl methanesulfonate formaldehyde
Mutations Mapped to the Genome

Type Location Additional Notes References point mutation 2L:19,170,480..19,170,480 comment=Site of nucleotide substitution in mutant inferred by FlyBase based on reported amino acid change. evidence=experimental na_change=C19170480T pr_change=Q779\|brat-PA,Q779\|brat-PB,Q779@\|brat-PC reported_pr_change=Q779@ (Arama et al., 2000)
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name AF195870 AAF13926

UniProtKB/Swiss-Prot	Q8MQJ9
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Amino acid replacement: Q779@. (Arama et al., 2000)
Cytology
Phenotypic Data
Phenotypic Class
	increased cell number \| germline clone (Harris et al., 2011) increased cell size \| germline clone (Harris et al., 2011) increased cell size \| somatic clone (Frank et al., 2002) lethal \| recessive (Wright, 1996, ) mitotic cell cycle defective (Lee et al., 2006) mitotic cell cycle defective \| somatic clone (Bello et al., 2006) neuroanatomy defective (Bello et al., 2006, Lee et al., 2006) neuroanatomy defective \| larval stage (with brat^DG19310) (Xiao et al., 2012) neuroanatomy defective \| larval stage (with brat^k06028) (Xiao et al., 2012) neuroanatomy defective \| somatic clone (Bello et al., 2006) tumorigenic (with brat¹⁴) (Woodhouse et al., 1998) tumorigenic \| third instar larval stage (Bello et al., 2006)
Phenotype Manifest In
	adult brain \| somatic clone (Bello et al., 2006) embryonic/larval brain (Bello et al., 2006) embryonic/larval brain \| cell autonomous \| somatic clone (Bello et al., 2006) female germline stem cell \| germline clone \| supernumerary (Harris et al., 2011) ganglion mother cell (Lee et al., 2006) neuroblast \| supernumerary (Lee et al., 2006) nucleolus \| somatic clone (Frank et al., 2002) type II neuroblast \| larval stage \| supernumerary (with brat^DG19310) (Xiao et al., 2012) type II neuroblast \| larval stage \| supernumerary (with brat^k06028) (Xiao et al., 2012)
Detailed Description
	Statement Reference brat[11]/brat[DG19310] larval brains contain supernumerary type II neuroblasts. brat[11]/brat[k06028] larval brains contain supernumerary type II neuroblasts. (Xiao et al., 2012) brat[11] germ line clones dispay an increased growth phenotype, with larger cells than wild-type. There is an increase in the number of germline stem cells in these mutants. (Harris et al., 2011) In late third instar brat¹¹ mutant larvae, brain hemispheres are markedly enlarged and characterized by cellular overgrowth whereas ventral ganglia appear normal. The central brain is characterized by dense cellular masses of numerous small and pleiomorphic cells in addition to a limited number of large cells. At earlier larval stages, brain hemispheres, brat¹¹ mutants brain hemispheres are the same overall size as wild-type larvae. brat¹¹ clones in the central brain of third instar larvae populate large areas of the brain hemispheres and are up to ten times larger than wild-type central brain clones: over 80% of the mutant clones comprise 200-1000 cells, while wild-type clones comprise >100 cells. In the early larval instar, brat¹¹ clones are clearly distinguishable and separated from one another, but by the late third instar almost all of the central brain appears to be covered by an indistinguishable clonal cell mass. Cells in brat¹¹ clones lack axonal processes. In the ventral ganglia, brat¹¹ clones are recovered at a similar frequency to wild-type clones. brat¹¹ clones induced in first instar larvae appear dramatically enlarged in size and cell number in the adult brain and appear to be mitotically active (according to phosphorylated His3 staining). (Bello et al., 2006) In brat[11] homozygous mutant larvae there is a dramatic increase in neuroblast number, over 500 by 96 hours after larval hatching and an estimated several thousand by 120 hours after larval hatching. This corresponds to a reduction in elav staining, indicating ectopic neuroblast generation at the expense of neurons. brat[11] neuroblasts generate GMC-sized progeny that are cell cycle delayed and continue to express neuroblast markers; some of these 'GMCs' differentiate into neurons, but many appear to develop into proliferative neuroblasts. (Lee et al., 2006) brat¹¹ homozygous somatic clones in third instar larvae are consistently larger than wild-type. the cells themselves are larger than individual wild-type cells. Mutant cells also have nucleoli that are 18 to 33% larger than wild-type cells, mutant dells contain 1.6 times more rRNA than control cells. (Frank et al., 2002) The median survival of adult hosts transplanted with brat¹¹/brat¹⁴ brain fragments is reduced compared to adult hosts transplanted with wild-type brain fragments. Cells from transplanted brat¹¹/brat¹⁴ brain fragments form at least one secondary tumour in the wild-type host in 84% of cases. Imaginal discs from brat¹¹/brat¹⁴ larvae form secondary tumours in 53% of hosts. (Woodhouse et al., 1998) Hemizygous larval brain tissue transplanted into the abdomens of adult female hosts shows unrestrained and invasive growth. (Wright, 1996)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressed by
Statement Reference brat¹¹ has neuroanatomy defective \| somatic clone phenotype, suppressible by pros^Scer\UAS.cMa/Scer\GAL4^αTub84B.PL (Bello et al., 2006) brat^DG19310/brat¹¹ has neuroanatomy defective \| larval stage phenotype, suppressible by klu[+]/klu^unspecified (Xiao et al., 2012) brat^k06028/brat¹¹ has neuroanatomy defective \| larval stage phenotype, suppressible \| somatic clone by klu^unspecified/klu^unspecified (Xiao et al., 2012)
Phenotype Manifest In
Suppressed by
Statement Reference brat¹¹ has embryonic/larval brain \| somatic clone phenotype, suppressible by pros^Scer\UAS.cMa/Scer\GAL4^αTub84B.PL (Bello et al., 2006) brat^DG19310/brat¹¹ has type II neuroblast \| supernumerary \| larval stage phenotype, suppressible by klu[+]/klu^unspecified (Xiao et al., 2012) brat^k06028/brat¹¹ has type II neuroblast \| supernumerary \| larval stage phenotype, suppressible \| somatic clone by klu^unspecified/klu^unspecified (Xiao et al., 2012)
Additional Comments
Genetic Interactions
Statement Reference klu[unspecified]/+ strongly suppresses the formation of supernumerary type II neuroblasts which is seen in brat[11]/brat[DG19310] larval brains. The formation of supernumerary type II neuroblasts is suppressed in homozygous klu[unspecified] type II neuroblast clones in brat[11]/brat[k06028] larval brains. (Xiao et al., 2012) Expression of pros^Scer\UAS.cMa, under the control of Scer\GAL4^αTub84B.PL, in brat¹¹ mutant larval clones significantly suppresses the overproliferation phenotype in these clones in the central larval brain. Over 90% of Scer\GAL4^αTub84B.PL>pros^Scer\UAS.cMa, brat¹¹ clones in the central brain have <100 cells, while over 80% of brat¹¹ clones have 200-1000 cells. (Bello et al., 2006)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Comments	Expression of brat^Scer\UAS.cSa under the control of Scer\GAL4^αTub84B.PL in brat¹¹ mutant clones partially rescues the overproliferation phenotype in the central larval brain. (Bello et al., 2006)
Stocks ( 0 )

Notes on Origin
Discoverer	Wright.

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 3 )
Reported As
Symbol Synonym	brat¹¹ (Bello et al., 2006, Wang et al., 2006, Lee et al., 2006, Harris et al., 2011, Xiao et al., 2012) l(2)37Cf¹¹ (Gateff and Mechler, 1989, ) l(2)347
Name Synonym
Secondary FlyBase IDs

References ( 12 )
Research paper	Xiao et al., 2012, Development 139(15): 2670--2680 klumpfuss distinguishes stem cells from progenitor cells during asymmetric neuroblast division. [FBrf0218804] Harris et al., 2011, Dev. Cell 20(1): 72--83 Brat Promotes Stem Cell Differentiation via Control of a Bistable Switch that Restricts BMP Signaling. [FBrf0212787] Bello et al., 2006, Development 133(14): 2639--2648 The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. [FBrf0194745] Lee et al., 2006, Dev. Cell 10(4): 441--449 Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. [FBrf0190211] Wang et al., 2006, Genes Dev. 20(24): 3453--3463 Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. [FBrf0194325] Frank et al., 2002, Development 129(2): 399--407 The Drosophila melanogaster gene brain tumor negatively regulates cell growth and ribosomal RNA synthesis. [FBrf0144835] Arama et al., 2000, Oncogene 19(33): 3706--3716 Mutations in the -propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain. [FBrf0129706] Woodhouse et al., 1998, Dev. Genes Evol. 207(8): 542--550 Growth, metastasis, and invasiveness of Drosophila tumors caused by mutations in specific tumor suppressor genes. [FBrf0102027] Wright, 1996, J. Hered. 87(3): 175--190 The Wilhelmine E. Key 1992 Invitational lecture. Phenotypic analysis of the Dopa decarboxylase gene cluster mutants in Drosophila melanogaster. [FBrf0089206] Stathakis et al., 1995, Genetics 141(2): 629--655 The genetic and molecular organization of the Dopa decarboxylase gene cluster of Drosophila melanogaster. [FBrf0084402] Wright et al., 1981, Chromosoma 83(1): 45--58 The genetics of dopa decarboxylase in Drosophila melanogaster. [FBrf0035993]
Review	Gateff and Mechler, 1989, Crit. Rev. Oncogen. 1: 221--245 Tumor-suppressor genes of Drosophila melanogaster. [FBrf0049455]

Allele Dmel\brat11

Allele Dmel\brat¹¹