Allele Dmel\Alk¹

General Information
Symbol	Dmel\Alk¹	Species	D. melanogaster
Name		FlyBase ID	FBal0157358
Feature type	allele	Associated gene	Dmel\Alk

Map ( GBrowse )
Allele class	loss of function allele
Mutagen	ethyl methanesulfonate
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 (Loren et al., 2003)
Mutagen	ethyl methanesulfonate (Loren et al., 2003)
Mutations Mapped to the Genome

Type Location Additional Notes References point mutation 2R:12,521,159..12,521,159 comment=Site of nucleic acid difference inferred by FlyBase based on reported amino acid change evidence=experimental na_change=C12521159T pr_change=Q306@\|Alk-PA reported_pr_change=Q306@ (Loren et al., 2003)
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Encodes a protein truncated in the first 'MAM' domain. (Englund et al., 2003) The stop mutation causes truncation of the Alk protein at the beginning of the first 'MAM' domain (Loren et al., 2003) Amino acid replacement: Q306@. (Loren et al., 2003)
Cytology
Phenotypic Data
Phenotypic Class
	cell migration defective \| embryonic stage 13 (Reim et al., 2012) increased cell death \| embryonic stage 13 (Reim et al., 2012) lethal \| embryonic stage \| recessive (Loren et al., 2003) lethal \| first instar larval stage \| recessive (Loren et al., 2003) locomotor rhythm defective (Rohrbough and Broadie, 2010) neuroanatomy defective \| somatic clone (Bazigou et al., 2007) neurophysiology defective (Rohrbough and Broadie, 2010)
Phenotype Manifest In
	axon & photoreceptor cell R8 \| somatic clone (Bazigou et al., 2007) embryonic/larval digestive system (Englund et al., 2003) embryonic/larval midgut (Loren et al., 2003) longitudinal visceral muscle primordium \| embryonic stage 13 (Reim et al., 2012) muscle founder cell \| embryonic stage (Englund et al., 2003) neuromuscular junction (Rohrbough and Broadie, 2010) optic cartridge \| somatic clone (Bazigou et al., 2007) visceral mesoderm (Bazigou et al., 2007, Loren et al., 2003, Englund et al., 2003)
Detailed Description
	Statement Reference Homozygous Alk[1] mutant longitudinal visceral muscle (LVM) founder cells in stage 12 embryos migrate normally towards the trunk visceral mesoderm (TVM) and very few dying cells are seen. At stage 13 the front migrating cells reach the anterior end of the trunk visceral mesoderm as in wild type. However during late stage 13 the migration becomes disordered and progressive founder cell death is seen. (Reim et al., 2012) Alk[1] heterozygous pupae are normal in size. (Gouzi et al., 2011) The central nervous system of Alk[1] mutants appears morphologically normal in terms of segmental nerve branching and segmental muscle patterning. Neuropil synaptic differentiation appears normal in these mutants, with comparable labeling intensity, density and distribution of presynaptic and postsynaptic labels. Alk[1] mutant neuromuscular junctions appear correctly and stereotypically formed and elaborated, with no examples of muscle innervation failure or synaptic targeting errors. mutant presynaptic active zones appear normally formed and with wild-type size. Homozygous Alk[1] mutants exhibit reduced hatching and mutant larval movement is typically sluggish and highly limited. Locomotory movement in Alk[1] mutants is decreased to 35% of the control level, characterised by slower contractions and extended pauses. Severely impaired and motionless larvae remain capable of briefly resuming movement when stimulated, suggesting a defect in the central circuit output driving locomotion. Alk[1] mutant neuromuscular junctions exhibit visible glutamate-driven muscle contractions, and consistently large and robust postsynaptic current amplitudes compared to controls. In Alk[1] mutant neuromuscular junctions, no large or patterned EJCs are recorded (maximum amplitude 429nA), and overall EJC frequency is below 1Hz in 80% of active cells. (Rohrbough and Broadie, 2010) Third instar larvae that have Alk function removed in the lamina target neurons, by the presence of Alk¹ clones, show normal R cell guidance. Additionally, adults with eyes made mutant for Alk¹ by the presence of clones show no R cell guidance defects. Adult mosaic Alk¹ animals, in which lamina target neurons are mutant for Alk¹, show R8 axon guidance defects. R8 cells exhibit thickened terminals and frequently fail to terminate in their appropriate layer. These axons either project into the R7 layer (7%), stop at the distal border of the medulla neuropil (12%), or project to neighbouring columns (9%). The vast majority of R7 terminals target normally but a small proportion extend into an adjacent medulla column. At the pupal stage, animals with lamina target neuron Alk¹ clones exhibit normal R cell projections up to 40 hours after puparium formation. At around 55 hours, R cell projection defects become apparent. These include thickened terminals, fasciculation with neighbouring columns and stalling of the axons at the distal medulla neuropil border ot projection into an adjacent column. In adults carrying Alk¹ clones in the lamina target neurons, the array of cartridges consisting of R1-R6 terminals in the lamina is disrupted and the size and shape of lamina cartridges is variable. Cartridges containing homozygous mutant target lamina are likely to be distributed randomly throughout the lamina. The visceral mesoderm is disrupted in stage 14 Alk¹ embryos. (Bazigou et al., 2007) R cells, target neurons and glia are normal in Alk¹ eye mosaic clones. (Bazigou et al., 2007) Alk¹ homozygous larvae do not ingest food, and lack discernible intestinal structures. In stage 13 Alk¹ homozygous embryos, the visceral mesoderm is disorganized. At stage 11, the earliest stage at which a mutant phenotype in the visceral mesoderm can clearly be observed, these embryos lack muscle founder cells. However, myoblasts do form in the visceral mesoderm, and go on to contribute to somatic muscle (i.e.- they are fusion competent.) (Englund et al., 2003) 55% of Alk¹/+ mutants die as embryos and the rest die as first-instar larvae. Alk¹ first-instar larvae are unable to eat as the visceral mesoderm is severely disrupted and no functional midgut is formed. (Loren et al., 2003)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Suppressor of
Statement Reference Alk¹/Alk[+] is a suppressor \| partially of learning defective \| adult stage phenotype of Nf1^E2 (Gouzi et al., 2011) Alk¹/Alk[+] is a suppressor \| partially of size defective \| pupal stage phenotype of Nf1^E2 (Gouzi et al., 2011)
Phenotype Manifest In
Additional Comments
Genetic Interactions
Statement Reference One copy of Alk[1] partially suppresses the small pupae phenotype seen in Nf1[E2] homozygotes by increasing cell size. The Nf1[E2] olfactory learning phenotype is also partially rescued. (Gouzi et al., 2011)
Xenogenetic Interactions
Statement Reference
Complementation & Rescue Data
Comments
Stocks ( 0 )

Notes on Origin
Discoverer
	Induced on: P{neoFRT}42D chromosome. (Loren et al., 2003) Selected as: a mutant that fails to complement the Df(2R)Alk-21 deficiency. (Loren et al., 2003)
External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 2 )
Reported As
Symbol Synonym	Alk¹ (Bazigou et al., 2007, Loren et al., 2003, Bazigou et al., 2007, Gouzi et al., 2011, Rohrbough and Broadie, 2010, Reim et al., 2012) DAlk¹ (Loren et al., 2003)
Name Synonym
Secondary FlyBase IDs

References ( 9 )
Research paper	Reim et al., 2012, Dev. Biol. 368(1): 28--43 The FGF8-related signals Pyramus and Thisbe promote pathfinding, substrate adhesion, and survival of migrating longitudinal gut muscle founder cells. [FBrf0218673] Gouzi et al., 2011, PLoS Genet. 7(9): e1002281 The receptor tyrosine kinase alk controls neurofibromin functions in Drosophila growth and learning. [FBrf0216258] Rohrbough and Broadie, 2010, Development 137(20): 3523--3533 Anterograde Jelly belly ligand to Alk receptor signaling at developing synapses is regulated by Mind the gap. [FBrf0211915] Bazigou et al., 2007, Cell 128(5): 961--975 Anterograde jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila. [FBrf0192674] Stute et al., 2004, Development 131(4): 743--754 Myoblast determination in the somatic and visceral mesoderm depends on Notch signalling as well as on milliways (mili[Alk]) as receptor for Jeb signalling. [FBrf0174588] Englund et al., 2003, Nature 425(6957): 512--516 Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion. [FBrf0167923] Loren et al., 2003, EMBO Rep. 4(8): 781--786 A crucial role for the Anaplastic lymphoma kinase receptor tyrosine kinase in gut development in Drosophila melanogaster. [FBrf0162095]
Supplementary material	Bazigou et al., 2007, Cell 128(5): Supplemental Data. Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila. [FBrf0199314] Loren et al., 2003, EMBO Rpts 4(8): [FBrf0199147]

Allele Dmel\Alk1

Allele Dmel\Alk¹