Allele Dmel\htl^AB42

General Information
Symbol	Dmel\htl^AB42	Species	D. melanogaster
Name		FlyBase ID	FBal0057264
Feature type	allele	Associated gene	Dmel\htl

Map ( GBrowse )
Allele class	amorphic allele - genetic evidence, loss of function allele
Mutagen	ethyl methanesulfonate
Recent Updates
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FB2013_03
FB2013_02
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Nature of the Allele
Allele class	amorphic allele - genetic evidence (Gisselbrecht et al., 1996) loss of function allele (Michelson et al., 1998, Mandal et al., 2004, Olofsson and Page, 2005)
Mutagen	ethyl methanesulfonate (Gisselbrecht et al., 1996)
Mutations Mapped to the Genome

Type Location Additional Notes References point mutation 3R:13,872,772..13,872,772 comment=The annotated and reported mutation locations differ by 15aa due to use of a different initiator methione. evidence=experimental na_change=C13872772T pr_change=R291\|htl-PC,R291\|htl-PA,R291@\|htl-PB reported_na_change=C935T reported_pr_change=R276@ (Gisselbrecht et al., 1996)
Associated Sequence Data
DDBJ / EMBL / GenBank	DNA sequence Protein sequence Name

UniProtKB/Swiss-Prot
UniProtKB/TrEMBL

Progenitor genotype
Nature of the lesion	Statement Reference Amino acid replacement: R276@. Nucleotide substitution: C935T. Mutant residue is just amino-terminal to the transmembrane domain. (Gisselbrecht et al., 1996)
Cytology
Phenotypic Data
Phenotypic Class
	cell migration defective \| embryonic stage 12 (Reim et al., 2012) increased cell death \| embryonic stage 13 (Reim et al., 2012) lethal \| embryonic stage \| recessive (Gisselbrecht et al., 1996) neuroanatomy defective \| embryonic stage 13 (Mandal et al., 2004)
Phenotype Manifest In
	axon & mechanosensory neuron & adult head, with Scer\GAL4^sca-537.4, htl^{DN.Scer\UAS.cMb} (Garcia-Alonso et al., 2000) axon & mechanosensory neuron & adult head (with htl^YY262), with Scer\GAL4^Bx-MS1096, Scer\GAL4^Mz1277, Scer\GAL4^twi.PB, htl^Scer\UAS.cMa (Garcia-Alonso et al., 2000) axon & ocellus sensory structure, with Scer\GAL4^sca-537.4, htl^{DN.Scer\UAS.cMb} (Garcia-Alonso et al., 2000) axon & ocellus sensory structure (with htl^YY262), with Scer\GAL4^Bx-MS1096, Scer\GAL4^Mz1277, Scer\GAL4^twi.PB, htl^Scer\UAS.cMa (Garcia-Alonso et al., 2000) cardioblast (Mandal et al., 2004, Michelson et al., 1998, Michelson et al., 1998) cardiogenic mesoderm (Mandal et al., 2004, Grigorian et al., 2011) corpus cardiacum primordium (De Velasco et al., 2004) embryonic/larval dorsal vessel (Imam et al., 1999) embryonic/larval dorsal vessel \| embryonic stage (Gisselbrecht et al., 1996) embryonic/larval pericardial cell (Michelson et al., 1998) embryonic/larval somatic muscle (Michelson et al., 1998) embryonic/larval somatic muscle \| dorsal (Michelson et al., 1998, Imam et al., 1999) embryonic pericardial cell (Mandal et al., 2004, Dossenbach et al., 2001) glial cell \| somatic clone (Franzdóttir et al., 2009) longitudinal visceral muscle fiber \| embryonic stage 13 (Mandal et al., 2004) longitudinal visceral muscle primordium \| embryonic stage 12 (Reim et al., 2012) longitudinal visceral muscle primordium \| embryonic stage 13 (Reim et al., 2012) lymph gland primordium (Mandal et al., 2004) mesoderm (Wilson et al., 2005, Schumacher et al., 2004, Michelson et al., 1998, Lin et al., 1999, McMahon et al., 2008, Murray and Saint, 2007, Michelson et al., 1998, Kadam et al., 2009) muscle founder cell (Schulz and Gajewski, 1999) pericardial cell (Michelson et al., 1998) presumptive embryonic salivary gland (Bradley et al., 2003) presumptive embryonic salivary gland (with htl^EMS2) (Bradley et al., 2003) somatic mesoderm (Gisselbrecht et al., 1996, Michelson et al., 1998) ventral furrow (McMahon et al., 2008) ventral nerve cord \| embryonic stage (Olofsson and Page, 2005) visceral mesoderm (Bradley et al., 2003, Gisselbrecht et al., 1996, Michelson et al., 1998)
Detailed Description
	Statement Reference Many of the LVM founder cells present in htl[AB42] mutant stage 12 embryos lose contact with the trunk visceral mesoderm (TVM) rather than spreading out across it. By stage 13 a large number of rounded and shrunken cells are seen some distance from the TVM. (Reim et al., 2012) Stage 11 and 12 mutant embryos have an abnormally shaped cardiogenic mesoderm. (Grigorian et al., 2011) Homozygous glial cell clones in the eye disc are only slightly smaller than wild-type clones, and the mutant cells migrate normally. The mutant clones comprise all glial cell types. However, the mutant cells do not adopt the typical wrapping phenotype, but instead are thin and spindle-shaped. (Franzdóttir et al., 2009) Homozygous embryos show defects in mesoderm spreading during stage 8, which results in the mesoderm forming a multilayered structure at stages 9-10 (in contrast to wild-type embryos where the mesoderm forms a single layer of cells at this stage). (Kadam et al., 2009) Mutant embryos show mesoderm cell defects that affect both collapse of the ventral furrow and spreading in the angular direction during gastrulation. The angular movement of upper furrow cells is strongly affected in the mutants. The last cells to invaginate in the mutant embryos, which make up the lower furrow, behave in a similar manner to wild-type furrow cells. (McMahon et al., 2008) In htl^AB42 embryos, the ventral cord is largely uncondensed compared to wild type. The migration of hemocytes during embryonic development appears normal. This phenotype is fully penetrant. (Olofsson and Page, 2005) Late stage mutant embryos show variable defects in the shape and location of the corpus cardiacum, from almost normal to stretched out and shifted posteriorly. (De Velasco et al., 2004) In stage-15 htl^AB42 mutant embryos, the lymph gland, cardioblasts and pericardial nephrocytes fails to develop from the cardiogenic mesoderm. (Mandal et al., 2004) htl[AB42] mutants exhibit defects in longitudinal visceral muscles. Morphology appears grossly normal in stage 11 and early stage 12 embryos. Longitudinal visceral muscle fibers are all but absent in stage 13 htl[AB42] mutant embryos, although circular fiber precursors are essentially normal. The amount of apoptotic cell death is generally increased in htl[AB42] mutants. (Mandal et al., 2004) Cell shape changes in the migrating mesoderm after invagination fail to occur in htl^AB42 homozygous embryos. Initially, the mesodermal epithelial tube extends further into the interior of the embryo when compared with wild type. Then, following mitosis in the invaginated mesoderm, the leading edge cells fail to extend dorsolaterally. Some migration does eventually take place and mesodermal cells do undergo some protrusive activity, but they fail to form a monolayer as in wild-type. As a result of these defects, by stage 10-12 there are no eve positive mesodermal cells in any hemisegment. In htl^AB42 homozygous embryo, cells at the base of the mesodermal tube at stage 7 fail to attach to underlying ectodermal cells and fail to align along the ventral midline. As in wild-type mesoderm, adherens junctions are lost from the mesoderm in htl^AB42 homozygotes after invagination. (Schumacher et al., 2004) No increase is seen in cardioblast numbers in the developing embryo. (Alvarez et al., 2003) Salivary gland shape and position is abnormal in homozygous and htl^AB42/htl^EMS2 embryos. The visceral mesoderm is disrupted in mutant embryos, showing gaps of variable width. (Bradley et al., 2003) Pericardial cells fail to form in mutant embryos, due to defects in mesoderm migration. (Dossenbach et al., 2001) Homozygous mutants display a defect in mesodermal cell migration. Embryos display an irregular layer where mesodermal cells remain clustered and fail to undergo their complete dorsal migration. (Fossett et al., 2000) The abnormal pathfinding behaviour in ocellar pioneer (OP) and bristle mechanosensory axons (BM) seen in individuals expressing htl^{DN.Scer\UAS.cMb} under the control of Scer\GAL4^sca-537.4 are enhanced by the addition of htl^AB42. htl^YY262/htl^AB42 flies rescued to the pupal stage by expression of htl^Scer\UAS.cMa under the control of three drivers (Scer\GAL4^Mz1277, Scer\GAL4^Bx-MS1096 and Scer\GAL4^twi.PB) gives axon guidance phenotypes in the head. Ocellar pioneer (OP) axons project into the epidermis, bristle mechanosensory (BM) axons fail to project into the brain, or stall in the epidermis or extend apart of epidermis. (Garcia-Alonso et al., 2000) Homozygous clones in the eye are wild-type. (Casci et al., 1999) Most of the cardial and dorsal somatic muscle cells fail in their dorsal migrations in htl^AB42 embryos. (Imam et al., 1999) Migration of the mesoderm fails to occur properly in homozygous embryos. (Lin et al., 1999) The majority of muscle precursors fail to form in htl^AB42 embryos. (Schulz and Gajewski, 1999) The mesodermal cells fail to undergo their normal dorsolateral migration in homozygous embryos and the cells remain aggregated instead of forming a monolayer. Later stage embryos show almost complete loss of cardial and pericardial cells and a marked reduction in the number of dorsal, lateral and ventral groups of somatic muscles. The failure of mesodermal migration is fully rescued by htl^Scer\UAS.cMa expressed under the control of Scer\GAL4^twi.PG. (Michelson et al., 1998) Mesoderm cells remain close to the ventral midline rather than migrating towards the dorsal ectoderm in homozygous embryos. All eve-positive mesodermal cells are missing. Most of the dorsal somatic muscles, cardial and pericardial cells fail to form. Large gaps are seen in the visceral mesoderm. (Michelson et al., 1998) Defect in cardiac development, residual pericardial cells are randomly distributed. Most of the dorsal somatic muscles are entirely missing and gaps are seen in the lateral and ventral muscle groups as well, there is both an increasing severity and variability in muscle loss from ventral to dorsal positions of embryos. Visceral musculature fails to undergo its normal morphogenesis (constrictions are not formed). Embryonic mesoderm appears as a multilayed collection of cells on either side of the extended germ band instead of a monolayer beneath the ectoderm. (Gisselbrecht et al., 1996)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Phenotype Manifest In
Enhanced by
Statement Reference htl^AB42 has mesoderm phenotype, enhanceable by ush¹ (Fossett et al., 2000)
Suppressed by
Statement Reference htl^AB42 has embryonic pericardial cell phenotype, suppressible \| partially by btl::htl^HB.Scer\UAS/Scer\GAL4^twi.PG (Dossenbach et al., 2001) htl^AB42 has embryonic pericardial cell phenotype, suppressible \| partially by htl::tor^Scer\UAS.cDa/Scer\GAL4^twi.PG (Dossenbach et al., 2001) htl^AB42 has embryonic pericardial cell phenotype, suppressible \| partially by Scer\GAL4^twi.PG/Egfr::htl^Scer\UAS.cDa (Dossenbach et al., 2001) htl^AB42 has longitudinal visceral muscle primordium \| embryonic stage 12 phenotype, suppressible \| partially by Scer\GAL4^tey-5053A/BacA\p35^Scer\UAS.cHa (Reim et al., 2012) htl^AB42 has longitudinal visceral muscle primordium \| embryonic stage 13 phenotype, suppressible \| partially by Scer\GAL4^tey-5053A/BacA\p35^Scer\UAS.cHa (Reim et al., 2012) htl^AB42 has mesoderm phenotype, suppressible \| partially by Scer\GAL4^twi.PG/btl::Egfr^{Scer\UAS.T:λ\cI-DD} (Michelson et al., 1998) htl^AB42 has mesoderm phenotype, suppressible \| partially by Scer\GAL4^twi.PG/Ras85D^{G13Q.Scer\UAS} (Michelson et al., 1998) htl^AB42 has mesoderm phenotype, suppressible by Scer\GAL4^twi.PG/btl^{Scer\UAS.T:λ\cI-DD} (Wilson et al., 2005)
NOT suppressed by
Statement Reference htl^AB42 has mesoderm phenotype, non-suppressible by Scer\GAL4^twi.PG/btl::Egfr^{Scer\UAS.T:λ\cI-DD} (Wilson et al., 2005) htl^AB42 has mesoderm phenotype, non-suppressible by Scer\GAL4^twi.PG/Cdc42^V12.Scer\UAS (Wilson et al., 2005) htl^AB42 has mesoderm phenotype, non-suppressible by Scer\GAL4^twi.PG/Pvr^{Scer\UAS.T:λ\cI-DD} (Wilson et al., 2005) htl^AB42 has mesoderm phenotype, non-suppressible by Scer\GAL4^twi.PG/Rac1^V12.Scer\UAS (Wilson et al., 2005)
Enhancer of
Statement Reference htl^AB42 is an enhancer of mesoderm phenotype of ush¹ (Fossett et al., 2000)
NOT Enhancer of
Statement Reference htl^AB42/htl[+] is a non-enhancer of neuroblast \| larval stage phenotype of trol¹³ (Park et al., 2003) htl^AB42/htl[+] is a non-enhancer of neuroblast \| larval stage phenotype of trol^p4 (Park et al., 2003)
Additional Comments
Genetic Interactions
Statement Reference Expression of btl^{Scer\UAS.T:λ\cI-DD} under the control of Scer\GAL4^twi.PG is able to induce bilaterally symmetrical flattening of the mesodermal tube onto the ectoderm in htl^AB42 embryos. Expression of either btl::Egfr^{Scer\UAS.T:λ\cI-DD} or Pvr^{Scer\UAS.T:λ\cI-DD} under the control of Scer\GAL4^twi.PG is not able to rescue either early contact between the mesoderm and ectoderm or symmetric flattening of the mesodermal tube in the early stages of mesoderm morphogenesis in htl^AB42 embryos. (Wilson et al., 2005) trol¹³/trol¹³; htl^AB42/+ larvae have normal numbers S phase neuroblast. (Park et al., 2003) Expression of btl::htl^HB.Scer\UAS or Egfr::htl^Scer\UAS.cDa under the control of Scer\GAL4^twi.PG in htl^AB42 embryos partially rescues pericardial cell development; in most cases only 12 to 18 (instead of 20) pericardial cells are properly determined and they often form small clusters instead of being aligned along the anterior-posterior axis. Expression of htl::tor^Scer\UAS.cDa under the control of Scer\GAL4^twi.PG in htl^AB42 embryos results in the formation of excess pericardial cells. (Dossenbach et al., 2001) Embryos heterozygous for htl^AB42 and ush¹ show a strong mesodermal migration defect. Also about half show a loss of cells from the dorsal mesoderm. (Fossett et al., 2000) The failure of mesodermal migration is partially rescued by Ras85D^{G13Q.Scer\UAS} expressed under the control of Scer\GAL4^twi.PG. (Michelson et al., 1998) The lack of eve-positive mesodermal cells seen in htl^AB42 embryos is partially rescued by btl::Egfr^{Scer\UAS.T:λ\cI-DD} expressed under the control of Scer\GAL4^twi.PG. (Michelson et al., 1998)
Xenogenetic Interactions
Statement Reference Expression of BacA\p35[Scer\UAS.cHa] under the control of Scer\GAL4[tey-5053A] partially suppresses the longitudinal visceral muscle (LVM) founder cell migration and survival defects seen in homozygous htl[AB42] stage 12/13 embryos. LVM founder cells regain much of the ability to migrate, however their tracks towards the anterior of the embryo are less efficient than in wild type with cells seen veering off in dorsal and ventral directions. (Reim et al., 2012)
Complementation & Rescue Data
Fails to complement	htl^EMS2 (Bradley et al., 2003) htl^J372 (Bradley et al., 2003) htl^YY262 (Bradley et al., 2003)
Rescued by	htl^AB42 is rescued by htl^Scer\UAS.cMa/Scer\GAL4^twi.PB (Schumacher et al., 2004) htl^AB42 is rescued by htl^Scer\UAS.cMa/Scer\GAL4^twi.PG (Michelson et al., 1998, Wilson et al., 2005, Bradley et al., 2003) htl^AB42 is rescued by Scer\GAL4^twi.PG/htl^Scer\UAS.cDa (Dossenbach et al., 2001) htl^AB42 is rescued by Scer\GAL4^twi.PG/htl^{Scer\UAS.T:λ\cI-DD} (Wilson et al., 2005)
Partially rescued by	htl^AB42 is partially rescued by htl^Scer\UAS.cMa/Scer\GAL4^tey-5053A (Reim et al., 2012) htl^AB42 is partially rescued by Scer\GAL4^tey-5053A/htl^{Scer\UAS.T:λ\cI-DD} (Reim et al., 2012) htl^AB42 is partially rescued by Scer\GAL4^twi.PG/htl^{Scer\UAS.T:λ\cI-DD} (Michelson et al., 1998, Lin et al., 1999) htl^YY262/htl^AB42 is partially rescued by htl^Scer\UAS.cMa/Scer\GAL4^twi.PB/Scer\GAL4^Mz1277/Scer\GAL4^Bx-MS1096 (Garcia-Alonso et al., 2000)
Not rescued by	htl^AB42 is not rescued by Scer\GAL4^twi.PG/htl^{K443A.Scer\UAS.T:λ\cI-DD,T:Ivir\HA1} (Wilson et al., 2005) htl^YY262/htl^AB42 is not rescued by htl^Scer\UAS.cMa/Scer\GAL4^twi.PB (Garcia-Alonso et al., 2000)
Comments	Expression of htl[Scer\UAS.cMa] under the control of Scer\GAL4[tey-5053A] rescues the longitudinal visceral muscle (LVM) founder cell death seen in htl[AB42] mutant stage 13 embryos. The founder cell migration defects are also partially rescued, however some cells acquire abnormal shapes, adhere to positions more distant from the TVM both dorsally and ventrally, and form clusters, resulting in missing LVM cells in the most anterior trunk segments. Expression of htl[Scer\UAS.T:λ\cI-DD] under the control of Scer\GAL4[tey-5053A] rescues the longitudinal visceral muscle (LVM) founder cell death seen in htl[AB42] mutant stage 13 embryos. The founder cell migration defects are also partially rescued, however some cells acquire abnormal shapes, adhere to positions more distant from the TVM both dorsally and ventrally, and form clusters, resulting in missing LVM cells in the most anterior trunk segments. (Reim et al., 2012) htl^Scer\UAS.cMa; Scer\GAL4^twi.PB rescues the migration of the mesoderm after invagination in htl^AB42 embryos. As a result the number of hemisegments with eve expressing mesodermal cells is 22, just as in wild-type. In contrast, htl^{Scer\UAS.T:λ\cI-DD} ; Scer\GAL4^twi.PB rescues the migration of the mesoderm after invagination in htl^AB42 embryos, but only partially rescues differentiation of the mesoderm (an average of 12.2 hemisegments per embryo have eve expressing mesodermal cells. (Schumacher et al., 2004) The addition of htl^Scer\UAS.cMa driven by Scer\GAL4^twi.PB, fails to rescue the lethality seen in htl^YY262/htl^AB42. However, when htl^Scer\UAS.cMa is driven by Scer\GAL4^Mz1277, Scer\GAL4^Bx-MS1096 and Scer\GAL4^twi.PB concurrently, some escaper pupae do survive. (Garcia-Alonso et al., 2000) htl^{Scer\UAS.T:λ\cI-DD} partially rescues the mesodermal phenotype of htl^AB42 embryos when expressed under the control of Scer\GAL4^twi.PG. (Michelson et al., 1998)
Stocks ( 1 )
Bloomington	5370 w^*; htl^AB42/TM3, P{ftz/lacC}SC1, ry^RK Sb¹ Ser¹
Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 4 )
Reported As
Symbol Synonym	AB42 (Gisselbrecht et al., 1996) heartless^AB42 (Alvarez et al., 2003) htl⁴² (Tian et al., 2004) htl^AB42 (Garcia-Alonso et al., 2000, Murray and Saint, 2007, Kadam et al., 2009, Franzdóttir et al., 2009, Kristiansen et al., 2005, Grigorian et al., 2011, Mariappa et al., 2011, Reim et al., 2012, Mandal et al., 2004)
Name Synonym
Secondary FlyBase IDs

References ( 29 )

Generate a list of	All references relating to this allele ( 29 )

List References by type	Research paper ( 29 )
Recent research papers ( 3 )
	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] Grigorian et al., 2011, Dev. Biol. 353(1): 105--118 The convergence of Notch and MAPK signaling specifies the blood progenitor fate in the Drosophila mesoderm. [FBrf0213410] Mariappa et al., 2011, Sci. Signal. 4(204): ra89 Protein O-GlcNAcylation Is Required for Fibroblast Growth Factor Signaling in Drosophila. [FBrf0217579] Show all research papers ...

Allele Dmel\htlAB42

Allele Dmel\htl^AB42