Allele Dmel\hpo^42-47

General Information
Symbol	Dmel\hpo^42-47	Species	D. melanogaster
Name		FlyBase ID	FBal0151857
Feature type	allele	Associated gene	Dmel\hpo

Allele class	loss of function allele
Mutagen	X ray
Recent Updates
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FB2013_03
FB2013_02
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Nature of the Allele
Allele class	loss of function allele (Willecke et al., 2006)
Mutagen	X ray (Wu et al., 2003)
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 An 18bp deletion in thee hpo ORF, leading to an in frame deletion of residues N166-T171 inclusive, in the predicted kinase domain. (Wu et al., 2003)
Cytology
Phenotypic Data
Phenotypic Class
	decreased cell death \| pupal stage \| somatic clone (Wu et al., 2003) hyperplasia \| somatic clone (Wu et al., 2003) lethal \| recessive (Wu et al., 2003) partially lethal - majority die \| pupal stage \| somatic clone (Wu et al., 2003) stress response defective \| somatic clone (Colombani et al., 2006) visible \| recessive (Hamaratoglu et al., 2006) visible \| somatic clone (Pellock et al., 2007)
Phenotype Manifest In
	adult cuticle \| somatic clone (Wu et al., 2003) adult external head \| somatic clone (Wu et al., 2003) adult head \| somatic clone (Polesello et al., 2006) eye (Hamaratoglu et al., 2006) eye \| P-stage \| somatic clone (Wu et al., 2003) eye \| somatic clone (Wu et al., 2003, Pellock et al., 2007) eye disc \| posterior \| somatic clone (Wu et al., 2003) inter-ommatidial cell \| pupal stage \| supernumerary (Hamaratoglu et al., 2006) ommatidium \| somatic clone (Wu et al., 2003) pigment cell \| ectopic \| somatic clone (Wu et al., 2003) wing disc \| larval stage \| somatic clone (Wu et al., 2003)
Detailed Description
	Statement Reference Adults containing homozygous clones represent only 2.1% of the population recovered after clones are induced using the eyFLP method (expected fraction of adults containing mutant clones is 50% if there is no effect of the mutant clones on viability). (Genevet et al., 2009) hpo[42-47] homozygous mutant clones generated in the male or female germline develop normally. In the testis 16 cells are observed per cyst, and cell size and morphology are indistinguishable from neighbouring control cells. (Sun et al., 2008) Eyes composed almost entirely of hpo[42-47] mutant tissue are overgrown and noticeably larger than control eyes. (Pellock et al., 2007) Apoptosis is reduced by up to 3-fold in hpo^42-47 clones of wing or eye discs in response to γ-rays compared to wild-type tissue. (Colombani et al., 2006) The mid-pupal retina of hpo[42-47]/hpo[42-47] animals contains a large excess of inter-ommatidial cells. The resulting adult eyes are distorted and lumpy. (Hamaratoglu et al., 2006) Animals bearing hpo^42-47 clones show an overgrowth phenotype in the head. (Polesello et al., 2006) When somatic clones of hpo^42-47 homozygous cells are generated throughout the eye disc using Scer\FLP1^ey.PN with P{neoFRT}42D, only 2% of animals survive the pupal stage and eclose. The resulting flies have enlarged, folded eyes, and excess head cuticle. The external ommatidial facets are frequently lost. Sectioning of these eyes reveals a normal complement of photoreceptor cells. However, spacing between photoreceptor clusters is increased due to the presence of extra interommatidial pigment cells. In somatic clones of hpo^42-47 homozygous cells in the late third instar eye disc, ommatidial clusters have the normal complement of differentiating photoreceptor cells, and R8 is specified at correct location and density emerging from the morphogenetic furrow. The spacing between adjacent ommatidial clusters is initially normal but increases at later stages (more posterior to the furrow), due to the presence of extra interommatidial cells. These extra cells seem to be due to a failure of uncommitted interommatidial cells to undergo cell cycle arrest posterior to the second mitotic wave. At least some of these cells continue to proliferate during early pupal development, as revealed by ectopic BrdU incorporation at 16 hr after puparium formation (APF). However, ectopic cell proliferation is undetectable beyond 24 hr APF. At 36 hr APF, cell death is suppressed in mutant clones, even though abundant apoptosis is detected in the neighboring wild-type cells. Cell death in hpo mutant clones is not simply delayed, since it could not be detected in mutant clones up to 48 hr APF. Somatic clones of hpo^42-47 homozygous cells in the adult cuticle are characterised by extensive tissue overgrowth and abnormally (roughly) textured cuticle in which cell-cell boundaries are apparent. The cells of hpo^42-47 homozygous somatic clones in wing discs during the growth phase have a doubling time of 12.2 hours, compared to 13.9 hours for wild-type cells. This is due to a proportional acceleration of all phases of the cell cycle, rather than an effect in any specific stage. (Wu et al., 2003)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressor of
Statement Reference hpo^42-47/hpo^42-47 is a suppressor \| partially of increased cell death \| third instar larval stage phenotype of Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF, ex^Scer\UAS.cBa (Hamaratoglu et al., 2006, Hamaratoglu et al., 2006) hpo^42-47 is a suppressor \| partially of increased cell death phenotype of p53^GMR.Ex (Colombani et al., 2006)
Phenotype Manifest In
Suppressed by
Statement Reference hpo^42-47 has adult external head \| somatic clone phenotype, suppressible by Hsap\STK3^hs.PW (Wu et al., 2003) hpo^42-47 has eye \| somatic clone phenotype, suppressible by Hsap\STK3^hs.PW (Wu et al., 2003) hpo^42-47 has ommatidium \| somatic clone phenotype, suppressible by Hsap\STK3^hs.PW (Wu et al., 2003)
Suppressor of
Statement Reference hpo^42-47/hpo[+] is a suppressor \| partially of eye phenotype of CycE^AR95/CycE^JP (Wu et al., 2003) hpo^42-47/hpo[+] is a suppressor \| partially of ommatidium phenotype of CycE^AR95/CycE^JP (Wu et al., 2003) hpo^42-47/hpo^42-47 is a suppressor \| partially of eye disc \| third instar larval stage phenotype of Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF, ex^Scer\UAS.cBa (Hamaratoglu et al., 2006, Hamaratoglu et al., 2006) hpo^42-47/hpo^42-47 is a suppressor of inter-ommatidial cell \| pupal stage phenotype of Scer\GAL4^GMR.PF/Scer\GAL4^GMR.PF, ex^Scer\UAS.cBa (Hamaratoglu et al., 2006, Hamaratoglu et al., 2006)
Additional Comments
Genetic Interactions
Statement Reference he loss of inter-ommatidial cells in the developing retinas of ex[Scer\UAS.cBa]; Scer\GAL4[GMR.PF] animals at the mid-pupal stage is completely suppressed by hpo[42-47]/hpo[42-47]. The resulting retinas have an excess of inter-ommatidial cells, just as hpo[42-47]/hpo[42-47] animals so. (Hamaratoglu et al., 2006) The head overgrowth phenotype of flies carrying hpo^42-47 clones is not significantly enhanced in a Rassf^X36 background. (Polesello et al., 2006) The small, rough eye phenotype of CycE^AR95/CycE^JP animals, is almost completely dominantly suppressed by hpo^42-47. (Wu et al., 2003)
Xenogenetic Interactions
Statement Reference The severe eye and heat cuticle deformities seen in adults carrying somatic clones of hpo^42-47 homozygous cells throughout the eye disc (generated using Scer\FLP1^ey.PN with P{neoFRT}42D) are almost completely suppressed by Hsap\STK3^hs.PW, given a suitable heat shock regime (60 minutes daily from 2nd instar until eclosion). (Wu et al., 2003)
Complementation & Rescue Data
Rescued by	hpo^42-47 is rescued by hpo^+t4.0 (Wu et al., 2003)
Comments
Stocks ( 0 )

Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 1 )
Reported As
Symbol Synonym	hpo^42-47 (Colombani et al., 2006, Colombani et al., 2006, Nolo et al., 2006, Dong et al., 2007, Fernández et al., 2011, Polesello et al., 2006, Emoto et al., 2006, Hamaratoglu et al., 2006, Oh and Irvine, 2008, Willecke et al., 2006, Sun et al., 2008, Genevet et al., 2009, Pellock et al., 2007, Zeng et al., 2010, Wu et al., 2008, Cho et al., 2006)
Name Synonym
Secondary FlyBase IDs

References ( 19 )
Research paper	Fernández et al., 2011, Development 138(11): 2337--2346 Actin-Capping Protein and the Hippo pathway regulate F-actin and tissue growth in Drosophila. [FBrf0213674] Yu et al., 2010, Dev. Cell 18(2): 288--299 Kibra Functions as a Tumor Suppressor Protein that Regulates Hippo Signaling in Conjunction with Merlin and Expanded. [FBrf0210017] Zeng et al., 2010, J. Cell. Physiol. 224(3): 766--774 Tumor suppressors Sav/scrib and oncogene ras regulate stem-cell transformation in adult Drosophila malpighian tubules. [FBrf0211181] Genevet et al., 2009, J. Cell Sci. 122(14): 2360--2370 The Hippo pathway regulates apical-domain size independently of its growth-control function. [FBrf0208280] Oh and Irvine, 2008, Development 135(6): 1081--1088 In vivo regulation of Yorkie phosphorylation and localization. [FBrf0204358] Sun et al., 2008, Dev. Dyn. 237(1): 270--275 Genes of Hippo signaling network act unconventionally in the control of germline proliferation in Drosophila. [FBrf0200427] Wu et al., 2008, Dev. Cell 14(3): 388--398 The TEAD/TEF family protein scalloped mediates transcriptional output of the hippo growth-regulatory pathway. [FBrf0204632] Dong et al., 2007, Cell 130(6): 1120--1133 Elucidation of a universal size-control mechanism in Drosophila and mammals. [FBrf0202397] Pellock et al., 2007, Dev. Biol. 304(1): 102--115 The Drosophila tumor suppressors Expanded and Merlin differentially regulate cell cycle exit, apoptosis, and Wingless signaling. [FBrf0200171] Cho et al., 2006, Nat. Genet. 38(10): 1142--1150 Delineation of a Fat tumor suppressor pathway. [FBrf0193283] Colombani et al., 2006, Curr. Biol. 16(14): 1453--1458 Dmp53 activates the hippo pathway to promote cell death in response to DNA damage. [FBrf0192785] Emoto et al., 2006, Nature 443(7108): 210--213 The tumour suppressor Hippo acts with the NDR kinases in dendritic tiling and maintenance. [FBrf0195286] Hamaratoglu et al., 2006, Nat. Cell Biol. 8(1): 27--36 The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis. [FBrf0191261] Nolo et al., 2006, Curr. Biol. 16(19): 1895--1904 The bantam microRNA is a target of the hippo tumor-suppressor pathway. [FBrf0194704] Polesello et al., 2006, Curr. Biol. 16(24): 2459--2465 The Drosophila RASSF homolog antagonizes the hippo pathway. [FBrf0192943] Willecke et al., 2006, Curr. Biol. 16(21): 2090--2100 The fat cadherin acts through the hippo tumor-suppressor pathway to regulate tissue size. [FBrf0194966] Huang et al., 2005, Cell 122(3): 421--434 The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. [FBrf0187228] Wu et al., 2003, Cell 114(4): 445--456 hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. [FBrf0161987]
Supplementary material	Colombani et al., 2006, Curr. Biol. 16(14): Supplemental data: Dmp53 activates the Hippo pathway to promote cell death in response to DNA damage. [FBrf0198723]

Allele Dmel\hpo42-47

Allele Dmel\hpo^42-47