Allele Dmel\fra⁴

General Information
Symbol	Dmel\fra⁴	Species	D. melanogaster
Name		FlyBase ID	FBal0057432
Feature type	allele	Associated gene	Dmel\fra

Allele class	amorphic allele - molecular evidence, amorphic allele - genetic evidence
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 (Kolodziej et al., 1996) amorphic allele - molecular evidence (Dorsten et al., 2007)
Mutagen	ethyl methanesulfonate (Kolodziej et al., 1996)
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
	neuroanatomy defective (Forsthoefel et al., 2005) neuroanatomy defective (with Df(2R)vg135) (Forsthoefel et al., 2005) neuroanatomy defective (with fra³) (Keleman and Dickson, 2001, Ratnaparkhi et al., 2002, Andrews et al., 2008, Mauss et al., 2009) neuroanatomy defective \| embryonic stage (with fra³) (Garbe et al., 2007, von Hilchen et al., 2010, Morikawa et al., 2011) neuroanatomy defective \| embryonic stage (with fra⁶) (Yang et al., 2009) neuroanatomy defective \| third instar larval stage (with fra³) (Morikawa et al., 2011)
Phenotype Manifest In
	anterior commissure (with fra³) (Keleman and Dickson, 2001, Andrews et al., 2008) Bolwig nerve (with fra³) (Andrews et al., 2008) class IV dendritic arborizing neuron \| third instar larval stage (with fra³) (Morikawa et al., 2011) commissure (Forsthoefel et al., 2005) commissure (with Df(2R)vg135) (Forsthoefel et al., 2005) commissure & embryo & axon (Kolodziej et al., 1996) commissure \| embryonic stage (with fra³) (Ratnaparkhi et al., 2002) dendrite (with fra³) (Mauss et al., 2009) dMP2 neuron, with Scer\GAL4⁶⁰⁵, fra^{ΔC.Scer\UAS.T:Hsap\MYC}/fra³ (Hiramoto et al., 2000) dMP2 neuron (with fra³) (Hiramoto et al., 2000) dMP2 neuron (with fra³), with Scer\GAL4⁶⁰⁵, fra^{ΔC.Scer\UAS.T:Hsap\MYC} (Hiramoto et al., 2000) dMP2 neuron (with fra^{ΔC.Scer\UAS.T:Hsap\MYC}), with Scer\GAL4⁶⁰⁵, fra³ (Hiramoto et al., 2000) EW neuron (with fra³) (Garbe et al., 2007) EW neuron (with fra⁶) (Yang et al., 2009) fascicle \| embryonic stage (with fra³) (Ratnaparkhi et al., 2002) interface glial cell (with fra³) (von Hilchen et al., 2010) intersegmental nerve (Winberg et al., 1998) lamina (Gong et al., 1999) longitudinal connective (with Df(2R)vg135) (Forsthoefel et al., 2005) longitudinal connective (with fra³) (Keleman and Dickson, 2001) longitudinal connective \| embryonic stage (Kolodziej et al., 1996) motor neuron (with fra³) (Mauss et al., 2009) posterior commissure (with fra³) (Keleman and Dickson, 2001, Andrews et al., 2008) presumptive embryonic salivary gland (with fra³) (Kolesnikov and Beckendorf, 2005) RP3 motor neuron (Winberg et al., 1998) ventral nerve cord commissure \| embryonic stage (with fra³) (Morikawa et al., 2011) ventral nerve cord commissure \| third instar larval stage (with fra³) (Morikawa et al., 2011)
Detailed Description
	Statement Reference fra[3]/fra[4] mutants exhibit virtually complete loss of commissural fascicles of C4da neurons. Furthermore the terminal processes of C4da axons in fra[3]/fra[4] mutants appear to lose the asymmetric orientation towards the midline. (Morikawa et al., 2011) Some hemisegments in fra[3]/fra[4] embryos have ectopic glial cell clusters in the dorsal periphery. (von Hilchen et al., 2010) In fra[3]/fra[4] mutant embryos, dendritic targeting to the midline is abolished in MN-VO4-6 and MN-VO4/5 projecting neurons. In fra[3]/fra[4] mutant embryos, 63% of MN-LL1 dendritic arbors lack the normally pronounced intermediate dendritic arborisation, while targeting of MN-DA3 dendrites is not significantly affected. MN-LL1 has a clearly reduced innervation of the intermediate neuropile in 63-64% of cases. (Mauss et al., 2009) fra[4]/fra[6] mutant embryos have normal commissure formation and a mild EW axon crossing defect. (Yang et al., 2009) 26% of fra[3]/fra[4] embryos show defects in axon guidance in the Bolwig's nerve. fra[3]/fra[4] embryos show defects in the commissures of the central nervous system; 2% of anterior commissures are absent, 4% of anterior commissures are thin, 3% of posterior commissures are absent and 8% of posterior commissures are thin. 8% of segments fail to separate the anterior and posterior commissures correctly. (Andrews et al., 2008) Heterozygous fra[4] stage 16 embryos do not display abnormal midline crossing axon tract projections. (Dorsten et al., 2007) EW axons frequently fail to cross the midline in fra[3]/fra[4] mutant embryos. The trajectories of the EG axons are unaffected in these mutants. (Garbe et al., 2007) 13% of segments have thin/missing commissures and 8% of segment have commissures with pathfinding errors in fra⁴/Df(2R)vg135 embryos. Breaks in the longitudinal connectives are seen in 10% of these embryos 23% of segments have thin/missing commissures and 13% of segment have commissures with pathfinding errors in fra⁴/fra⁴ embryos. (Forsthoefel et al., 2005) fra³/fra⁴ transheterozygote embryos show salivary gland guidance defects. Most mutants have salivary glands that lie parallel to the CNS midline as in wild type. However, in 4% of mutants, the glands curve laterally away from the midline and in 2% of mutants, the glands curve medially toward the midline. (Kolesnikov and Beckendorf, 2005) fra³/fra⁴ embryos exhibit breaks in Con-positive commissural axons and longitudinal tracts. (Ratnaparkhi et al., 2002) dMP2 axons make pathfinding errors in fra³/fra⁴ mutant embryos, often extending laterally, turning anteriorly or stalling. Expression of fra^{ΔC.Scer\UAS.T:Hsap\MYC} under the control of Scer\GAL4⁶⁰⁵ in fra³/fra⁴ embryos results in abnormal spreading of the dMP2 growth cone over the region of induced ectopic NetB accumulation. (Hiramoto et al., 2000) fra⁴ mutant clones in the eye show no discernable projection defects. fra⁴ mutant clones in the developing lamina are innervated abnormally. Wild type retinal fibers are incapable of innervating lamina target regions that lack fra function. Retinal fibers consistently avoid fra mutant patches and reroute to fra⁺ areas. Rerouting can occur in both the a-p and d-v axis. Incoming retinal fibers respect clonal boundaries. (Gong et al., 1999) The RP3 axon extends dorsally past and just adjacent to muscles 7 and 6 and then reached back to innervate them. RP3 neuron may extend into its normal muscle domain but fail to innervate muscles 7 and 6. The ISNb fails to innervate muscles 7 and 6. Scer\GAL4^how-24B-mediated expression of NetA^Scer\UAS.cHa or NetB^Scer\UAS.cHa allows the axons of the transverse nerve to ectopically innervate muscles 7 and 6, loss of fra function suppresses this phenotype. (Winberg et al., 1998) In fra³/fra⁴ embryos 12% of anterior commissures and 43% of posterior commissures in abdominal segments A1-A7 are thin or absent. Commissures that appear to have normal thickness are often less well organised than normal. Occasional breaks are also observed in the longitudinal tracts. A subset of motor axons exit the ventral CNS in the intersegmental nerve and extend dorsally, in fra³/fra⁴ embryos the axons often extend a colateral branch into an adjacent segment or make inappropriate contacts with dorsal muscles when they reach the dorsal muscle region. (Kolodziej et al., 1996)
External Data
Linkouts
Interactions
	Show the genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement Reference Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, enhanceable by Abl¹/Abl[+] (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, enhanceable by Abl⁴/Abl[+] (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, enhanceable by Abl⁴/Abl¹ (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, enhanceable by Df(3L)Fpa1/+ (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, enhanceable by trio[+]/trio^IMP159.4 (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, enhanceable by trio[+]/trio^M89 (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, enhanceable by trio^M89/trio^IMP159.4 (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by Abl¹/Abl[+] (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by Abl⁴/Abl[+] (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by Abl⁴/Abl¹ (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by Df(3L)Fpa1/+ (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by trio[+]/trio^IMP159.4 (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by trio[+]/trio^M89 (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by trio[+]/trio^S036810 (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by trio^M89/trio^IMP159.4 (Forsthoefel et al., 2005) fra⁴ has neuroanatomy defective phenotype, enhanceable by trio^M89/trio^S036810 (Forsthoefel et al., 2005) fra⁶/fra⁴ has neuroanatomy defective \| embryonic stage phenotype, enhanceable by comm^E39/comm[+] (Yang et al., 2009)
NOT Enhanced by
Statement Reference Dscam⁰⁵⁵¹⁸, fra⁴ has neuroanatomy defective phenotype, non-enhanceable by Dscam3^c02826/Dscam3^c02826 (Andrews et al., 2008, Andrews et al., 2008)
Suppressed by
Statement Reference Df(2R)vg135/fra⁴ has neuroanatomy defective phenotype, suppressible \| partially by ena[+]/ena^GC10 (Forsthoefel et al., 2005) fra³/fra⁴ has neuroanatomy defective phenotype, suppressible by fra::unc-5^{fra.CD.Scer\UAS}/Scer\GAL4^elav.PLu (Keleman and Dickson, 2001)
NOT suppressed by
Statement Reference fra³/fra⁴ has neuroanatomy defective \| embryonic stage phenotype, non-suppressible by fra::robo^{Scer\UAS.FΔC.T:Hsap\MYC}/Scer\GAL4^elav.PLu (Garbe et al., 2007) fra³/fra⁴ has neuroanatomy defective phenotype, non-suppressible by Scer\GAL4^elav-C155/Gαq^{Q203L.Scer\UAS} (Ratnaparkhi et al., 2002)
Enhancer of
Statement Reference fra⁴/fra[+] is an enhancer of neuroanatomy defective \| recessive phenotype of N^l1N-ts1 (Kuzina et al., 2011)
NOT Enhancer of
Statement Reference fra⁴/fra[+] is a non-enhancer of neuroanatomy defective phenotype of Df(3L)Fpa1/trio^IMP159.4 (Forsthoefel et al., 2005) fra⁴/fra[+] is a non-enhancer of neuroanatomy defective phenotype of trio^M89/trio^IMP159.4 (Forsthoefel et al., 2005)
Suppressor of
Statement Reference fra³/fra⁴ is a suppressor \| partially of neuroanatomy defective phenotype of Scer\GAL4^ap-md544, unc-5^{Scer\UAS.T:Ivir\HA1,T:SS-wg} (Keleman and Dickson, 2001) fra³/fra⁴ is a suppressor of neuroanatomy defective \| somatic clone \| third instar larval stage phenotype of Scer\GAL4^ppk.PG, Trim9^{Scer\UAS.T:Ivir\HA1} (Morikawa et al., 2011) fra³/fra⁴ is a suppressor of neuroanatomy defective phenotype of Gαq^{Q203L.Scer\UAS}, Scer\GAL4^elav-C155 (Ratnaparkhi et al., 2002) fra⁴/fra[+] is a suppressor \| partially of neuroanatomy defective \| embryonic stage 16 phenotype of Cdc42^V12.Scer\UAS, Scer\GAL4^ftz.ng (Dorsten et al., 2007) fra⁴/fra[+] is a suppressor \| partially of neuroanatomy defective \| embryonic stage 16 phenotype of Rac1^V12.Scer\UAS, Scer\GAL4^ftz.ng (Dorsten et al., 2007) fra⁴/fra[+] is a suppressor \| partially of neuroanatomy defective phenotype of Ggal\MLCK^ct.Scer\UAS, Scer\GAL4^ftz.ng (Kim et al., 2002)
NOT Suppressor of
Statement Reference fra³/fra⁴ is a non-suppressor of neuroanatomy defective phenotype of Scer\GAL4^elav.PLu, unc-5^{Scer\UAS.T:Ivir\HA1,T:SS-wg} (Keleman and Dickson, 2001) Scer\GAL4^ap-md544, fra³, fra⁴, fra^Scer\UAS.cKa is a non-suppressor of neuroanatomy defective phenotype of Scer\GAL4^ap-md544, unc-5^{Scer\UAS.T:Ivir\HA1,T:SS-wg} (Keleman and Dickson, 2001)
Other
Statement Reference Df(1)NP5/+, fra⁴ has neuroanatomy defective \| dominant phenotype (Andrews et al., 2008) Df(2R)en-SFX31, fra⁴ has neuroanatomy defective phenotype (Joly et al., 2007) Dscam⁰⁵⁵¹⁸/Dscam[+], fra⁴ has neuroanatomy defective \| dominant phenotype (Andrews et al., 2008)
Phenotype Manifest In
Enhanced by
Statement Reference Df(2R)vg135/fra⁴ has commissure phenotype, enhanceable by Abl¹/Abl[+] (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has commissure phenotype, enhanceable by Abl⁴/Abl[+] (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has commissure phenotype, enhanceable by Abl⁴/Abl¹ (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has commissure phenotype, enhanceable by Df(3L)Fpa1/+ (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has commissure phenotype, enhanceable by trio[+]/trio^IMP159.4 (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has commissure phenotype, enhanceable by trio[+]/trio^M89 (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has commissure phenotype, enhanceable by trio^M89/trio^IMP159.4 (Forsthoefel et al., 2005) fra³/fra⁴ has presumptive embryonic salivary gland phenotype, enhanceable by mew^M6 (Kolesnikov and Beckendorf, 2005) fra⁴ has commissure phenotype, enhanceable by Abl¹/Abl[+] (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by Abl⁴/Abl[+] (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by Abl⁴/Abl¹ (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by Df(3L)Fpa1/+ (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by trio[+]/trio^IMP159.4 (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by trio[+]/trio^M89 (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by trio[+]/trio^S036810 (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by trio^M89/trio^IMP159.4 (Forsthoefel et al., 2005) fra⁴ has commissure phenotype, enhanceable by trio^M89/trio^S036810 (Forsthoefel et al., 2005) fra⁶/fra⁴ has EW neuron phenotype, enhanceable by comm^E39/comm[+] (Yang et al., 2009)
NOT Enhanced by
Statement Reference Df(2R)vg135/fra⁴ has longitudinal connective phenotype, non-enhanceable by Abl⁴/Abl¹ (Forsthoefel et al., 2005) Df(2R)vg135/fra⁴ has longitudinal connective phenotype, non-enhanceable by trio^M89/trio^IMP159.4 (Forsthoefel et al., 2005) Dscam⁰⁵⁵¹⁸, fra⁴ has Bolwig nerve phenotype, non-enhanceable by Dscam3^c02826/Dscam3^c02826 (Andrews et al., 2008, Andrews et al., 2008)
Suppressed by
Statement Reference Df(2R)vg135/fra⁴ has commissure phenotype, suppressible \| partially by ena[+]/ena^GC10 (Forsthoefel et al., 2005) fra³/fra⁴ has anterior commissure phenotype, suppressible by fra::unc-5^{fra.CD.Scer\UAS}/Scer\GAL4^elav.PLu (Keleman and Dickson, 2001) fra³/fra⁴ has longitudinal connective phenotype, suppressible by fra::unc-5^{fra.CD.Scer\UAS}/Scer\GAL4^elav.PLu (Keleman and Dickson, 2001) fra³/fra⁴ has posterior commissure phenotype, suppressible by fra::unc-5^{fra.CD.Scer\UAS}/Scer\GAL4^elav.PLu (Keleman and Dickson, 2001)
NOT suppressed by
Statement Reference fra³/fra⁴ has commissure \| embryonic stage phenotype, non-suppressible by Scer\GAL4^elav-C155/Gαq^{Q203L.Scer\UAS} (Ratnaparkhi et al., 2002) fra³/fra⁴ has fascicle \| embryonic stage phenotype, non-suppressible by Scer\GAL4^elav-C155/Gαq^{Q203L.Scer\UAS} (Ratnaparkhi et al., 2002)
Enhancer of
Statement Reference fra³/fra⁴ is an enhancer of commissure \| embryonic stage phenotype of Gαq^{Q203L.Scer\UAS}, Scer\GAL4^elav-C155 (Ratnaparkhi et al., 2002) fra³/fra⁴ is an enhancer of fascicle \| embryonic stage phenotype of Gαq^{Q203L.Scer\UAS}, Scer\GAL4^elav-C155 (Ratnaparkhi et al., 2002) fra⁴/fra[+] is an enhancer of pioneer neuron phenotype of N^l1N-ts1 (Kuzina et al., 2011)
NOT Enhancer of
Statement Reference fra⁴/fra[+] is a non-enhancer of commissure phenotype of Df(3L)Fpa1/trio^IMP159.4 (Forsthoefel et al., 2005) fra⁴/fra[+] is a non-enhancer of commissure phenotype of trio^M89/trio^IMP159.4 (Forsthoefel et al., 2005)
Suppressor of
Statement Reference fra³/fra⁴ is a suppressor \| partially of ventral nerve cord phenotype of Scer\GAL4^ap-md544, unc-5^{Scer\UAS.T:Ivir\HA1,T:SS-wg} (Keleman and Dickson, 2001) fra³/fra⁴ is a suppressor of abdominal anterior ventral multidendritic neuron vdaa phenotype of Scer\GAL4^ppk.PG, Trim9^{Scer\UAS.T:Ivir\HA1} (Morikawa et al., 2011) fra³/fra⁴ is a suppressor of presumptive embryonic salivary gland phenotype of sli² (Kolesnikov and Beckendorf, 2005) fra⁴/fra[+] is a suppressor \| partially of longitudinal connective phenotype of Ggal\MLCK^ct.Scer\UAS, Scer\GAL4^ftz.ng (Kim et al., 2002) fra⁴/fra[+] is a suppressor \| partially of midline crossing tract \| embryonic stage 16 phenotype of Cdc42^V12.Scer\UAS, Scer\GAL4^ftz.ng (Dorsten et al., 2007) fra⁴/fra[+] is a suppressor \| partially of midline crossing tract \| embryonic stage 16 phenotype of Rac1^V12.Scer\UAS, Scer\GAL4^ftz.ng (Dorsten et al., 2007) fra⁴/fra[+] is a suppressor \| partially of ventral nerve cord commissure \| embryonic stage 16 phenotype of Cdc42^V12.Scer\UAS, Scer\GAL4^ftz.ng (Dorsten et al., 2007) fra⁴/fra[+] is a suppressor \| partially of ventral nerve cord commissure \| embryonic stage 16 phenotype of Rac1^V12.Scer\UAS, Scer\GAL4^ftz.ng (Dorsten et al., 2007) fra⁴ is a suppressor of transverse nerve phenotype of NetA^Scer\UAS.cHa, Scer\GAL4^how-24B/Scer\GAL4^how-24B (Winberg et al., 1998) fra⁴ is a suppressor of transverse nerve phenotype of NetB^Scer\UAS.cHa, Scer\GAL4^how-24B/Scer\GAL4^how-24B (Winberg et al., 1998)
NOT Suppressor of
Statement Reference fra³, fra⁴, fra^Scer\UAS.cKa is a non-suppressor of ventral nerve cord phenotype of Scer\GAL4^ap-md544, unc-5^{Scer\UAS.T:Ivir\HA1,T:SS-wg} (Keleman and Dickson, 2001) fra³/fra⁴ is a non-suppressor of anterior commissure phenotype of Scer\GAL4^elav.PLu, unc-5^{Scer\UAS.T:Ivir\HA1,T:SS-wg} (Keleman and Dickson, 2001) fra³/fra⁴ is a non-suppressor of posterior commissure phenotype of Scer\GAL4^elav.PLu, unc-5^{Scer\UAS.T:Ivir\HA1,T:SS-wg} (Keleman and Dickson, 2001)
Other
Statement Reference Df(1)NP5/+, fra⁴ has Bolwig nerve phenotype (Andrews et al., 2008) Df(2R)en-SFX31, fra⁴ has anterior commissure phenotype (Joly et al., 2007) Df(2R)en-SFX31, fra⁴ has lateral tract phenotype (Joly et al., 2007) Df(2R)en-SFX31, fra⁴ has posterior commissure phenotype (Joly et al., 2007) Df(2R)en-SFX31, fra⁴ has ventral nerve cord phenotype (Joly et al., 2007) Dscam⁰⁵⁵¹⁸/Dscam[+], fra⁴ has Bolwig nerve phenotype (Andrews et al., 2008) fra³/fra⁴, mew^M6 has presumptive embryonic salivary gland phenotype (Kolesnikov and Beckendorf, 2005, Kolesnikov and Beckendorf, 2005) NetB^Scer\UAS.cHa, Scer\GAL4⁶⁰⁵, fra³/fra⁴ has dMP2 neuron phenotype (Hiramoto et al., 2000, Hiramoto et al., 2000)
Additional Comments
Genetic Interactions
Statement Reference The N[l1N-ts1] pioneer axon phenotype is strongly enhanced by heterozygosity for fra[4]. (Kuzina et al., 2011) A fra[4] mutant background suppresses the ectopic contralateral projections seen when Trim9[Scer\UAS.T:Ivir\HA1] is expressed in v'ada neurons under the control of Scer\GAL4[ppk.PG]. (Morikawa et al., 2011) The commissural defects seen in fra[4]/fra[6] embryos are enhanced in a heterozygous comm[E39]/+ genetic background as shown by missing and thin commissures in many segments, as well as an increased frequency of non-crossing defects in a subset of of commissural neurons. (Yang et al., 2009) 67% of Dscam[05518]/Dscam[05518] fra[4]/fra[4] embryos show defects in axon guidance in the Bolwig's nerve. The penetrance of the axon guidance defect phenotype that is seen in the Bolwig's nerve of Dscam[05518]/Dscam[05518] fra[4]/fra[4] double mutant embryos is not increased by addition of Dscam3[c02826]/Dscam3[c02826]. 30% of Df(1)NP5/+ ; fra[4]/+ embryos show defects in axon guidance in the Bolwig's nerve. 22.5% of Dscam[05518]/+ ; fra[4]/+ embryos show defects in axon guidance in the Bolwig's nerve. Dscam[05518] fra[4] embryos show defects in the commissures of the central nervous system; 9% of anterior commissures are absent, 24% of anterior commissures are thin, 5% of posterior commissures are absent and 39% of posterior commissures are thin. 51% of segments fail to separate the anterior and posterior commissures correctly. fra[3]/fra[4] Dscam3[c02826] embryos show defects in the commissures of the central nervous system; 2% of anterior commissures are absent, 3% of anterior commissures are thin, 1% of posterior commissures are absent and 9% of posterior commissures are thin. 48% of segments fail to separate the anterior and posterior commissures correctly. fra[4] Abl[4] embryos show defects in the commissures of the central nervous system; 14% of anterior commissures are absent, 24% of anterior commissures are thin, 16% of posterior commissures are absent and 24% of posterior commissures are thin. 19% of segments fail to separate the anterior and posterior commissures correctly. Dscam[05518] fra[4] Dscam3[c02826] embryos show defects in the commissures of the central nervous system; 39% of anterior commissures are absent, 51% of anterior commissures are thin, 36% of posterior commissures are absent and 55% of posterior commissures are thin. 5% of segments fail to separate the anterior and posterior commissures correctly. Dscam[05518] fra[4] Abl[4] embryos show defects in the commissures of the central nervous system; 98% of anterior commissures are absent, 2% of anterior commissures are thin and 100% of posterior commissures are absent. (Andrews et al., 2008) Heterozygous fra[4] partially suppresses the incorrect midline crossing phenotype of ventral nerve cord axons in embryos overexpressing Cdc42[V12.Scer\UAS] via Scer\GAL4[ftz.ng]. Heterozygous fra[4] partially suppresses the incorrect midline crossing phenotype of ventral nerve cord axons in embryos overexpressing Rac1[V12.Scer\UAS] via Scer\GAL4[ftz.ng]. (Dorsten et al., 2007) Expression of fra::robo[Scer\UAS.FΔC.T:Hsap\MYC]under the control of Scer\GAL4[elav.PLu] fails to rescue the fra[3]/fra[4] axon guidance phenotypes. (Garbe et al., 2007) Approximately 66% of fra[4]/Df(2R)en-SFX31 double mutants exhibit defects in axonal pathfinding. Stage 15 embryos display dramatic defects in ventral nerve cord architecture, with the posterior commissures missing or fused with the anterior commissures, and longitudinal tracts thinner. Nearly all the segments are affected in these embryos. (Joly et al., 2007) The frequency of the loss of commissure phenotype seen in Abl¹/Abl⁴ embryos is not enhanced by fra⁴/+, but the frequency of commissures with pathfinding errors is increased in the fra⁴/+; Abl¹/Abl⁴ embryos compared to Abl¹/Abl⁴. (Forsthoefel et al., 2005) In mew^M6/Y; fra³/fra⁴ double mutant embryos, the misguided salivary gland phenotype is modified, compared to that of each single mutant. Like fra³/fra⁴ mutants, the majority (75%) of misguided glands curve laterally, but levels of penetrance are high, similar to mew^M6/Y single mutants. In sli²; fra³/fra⁴ double mutants, the penetrance of the salivary gland guidance defects is by 40% compared to sli² single mutants. (Kolesnikov and Beckendorf, 2005) A reduction in midline crossing is observed upon removal of two copies of the fra gene in Scer\GAL4^elav-C155/Gα49B^{Q203L.Scer\UAS};fra³/fra⁴, from 48.10% of abdominal segments exhibiting midline crossover in Scer\GAL4^elav-C155/Gα49B^{Q203L.Scer\UAS} embryos to 5.3% in Scer\GAL4^elav-C155/Gα49B^{Q203L.Scer\UAS};fra³/fra⁴ mutant embryos. Embryos of the genotype Scer\GAL4^elav-C155/Gα49B^{Q203L.Scer\UAS} and fra³/fra⁴ exhibit breaks in Con-positive commissural axons and longitudinal tracts, similar to Scer\GAL4^elav-C155/Gα49B^{Q203L.Scer\UAS}; fra³/fra⁴ embryos, indicating that Gα49B does not have an effect on the fra mutant phenotype. (Ratnaparkhi et al., 2002) Expression of NetB^Scer\UAS.cHa under the control of Scer\GAL4⁶⁰⁵ in fra³/fra⁴ embryos results in abnormal spreading of the dMP2 growth cone over the region of ectopic NetB expression. (Hiramoto et al., 2000)
Xenogenetic Interactions
Statement Reference The midline crossover phenotype caused expression of Ggal\MLCK^ct.Scer\UAS under the control of Scer\GAL4^ftz.ng is partially suppressed by fra⁴/+. (Kim et al., 2002)
Complementation & Rescue Data
Rescued by	fra³/fra⁴ is rescued by fra^Scer\UAS.cKa/Scer\GAL4^elav.PLu (Keleman and Dickson, 2001) fra³/fra⁴ is rescued by fra^Scer\UAS.cKa/Scer\GAL4^eve.CQ2 (Mauss et al., 2009) fra³/fra⁴ is rescued by fra^{Scer\UAS.T:Hsap\MYC}/Scer\GAL4^elav.PLu (Garbe et al., 2007) fra³/fra⁴ is rescued by fra^{ΔP1.Scer\UAS.T:Hsap\MYC}/Scer\GAL4^eg-Mz360 (Garbe et al., 2007) fra³/fra⁴ is rescued by Scer\GAL4⁶⁰⁵/fra^Scer\UAS.cKa (Hiramoto et al., 2000) fra³/fra⁴ is rescued by Scer\GAL4^eg-Mz360/fra^{Scer\UAS.T:Hsap\MYC} (Garbe et al., 2007) fra³/fra⁴ is rescued by Scer\GAL4^eg-Mz360/fra^{Scer\UAS.T:Ivir\HA1} (Garbe et al., 2007) fra³/fra⁴ is rescued by Scer\GAL4^eg-Mz360/fra^{ΔP1ΔP2.Scer\UAS.T:Hsap\MYC} (Garbe et al., 2007) fra³/fra⁴ is rescued by Scer\GAL4^eg-Mz360/fra^{ΔP2.Scer\UAS.T:Hsap\MYC} (Garbe et al., 2007) fra³/fra⁴ is rescued by Scer\GAL4^gcm.PU/fra^Scer\UAS.cKa (von Hilchen et al., 2010)
Partially rescued by	fra³/fra⁴ is partially rescued by fra^Scer\UAS.cKa/Scer\GAL4¹⁴⁰⁷ (Kolodziej et al., 1996) fra³/fra⁴ is partially rescued by Scer\GAL4^MZ1580/fra^Scer\UAS.cKa (von Hilchen et al., 2010) fra³/fra⁴ is partially rescued by Scer\GAL4^ppk.PG/fra^Scer\UAS.cKa (Morikawa et al., 2011)
Not rescued by	fra³/fra⁴ is not rescued by fra^{ΔC.Scer\UAS.T:Ivir\HA1}/Scer\GAL4^elav.PLu (Garbe et al., 2007) fra³/fra⁴ is not rescued by Scer\GAL4^15J2/fra^Scer\UAS.cKa (Hiramoto et al., 2000) fra³/fra⁴ is not rescued by Scer\GAL4^eg-Mz360/fra^{Scer\UAS.T:Myr-Src64B,T:Hsap\MYC} (Garbe et al., 2007) fra³/fra⁴ is not rescued by Scer\GAL4^eg-Mz360/fra^{ΔP3.5.Scer\UAS.T:Hsap\MYC} (Garbe et al., 2007) fra³/fra⁴ is not rescued by Scer\GAL4^eg-Mz360/fra^{ΔP3.Scer\UAS.T:Hsap\MYC} (Garbe et al., 2007) fra³/fra⁴ is not rescued by Scer\GAL4^elav.PU/fra^Scer\UAS.cKa (von Hilchen et al., 2010) fra³/fra⁴ is not rescued by Scer\GAL4^how-24B/Scer\GAL4^how-24B/fra^Scer\UAS.cKa (Kolodziej et al., 1996) fra³/fra⁴ is not rescued by Scer\GAL4^Mz605/fra^Scer\UAS.cKa (von Hilchen et al., 2010) fra³/fra⁴ is not rescued by Scer\GAL4^pros.PMG/fra^Scer\UAS.cKa (von Hilchen et al., 2010) fra³/fra⁴ is not rescued by Scer\GAL4^repo/fra^Scer\UAS.cKa (von Hilchen et al., 2010)
Comments	Expression of fra[Scer\UAS.cKa] in C4da neurons under the control of Scer\GAL4[ppk.PG] partially rescues the axonal defects seen in fra[3]/fra[4] mutants. (Morikawa et al., 2011) Expression of fra[Scer\UAS.cKa] under the control of Scer\GAL4[gcm.PU] rescues the defects in interface glial cell migration seen in fra[3]/fra[4] embryos. Expression of fra[Scer\UAS.cKa] under the control of Scer\GAL4[MZ1580] weakly rescues the defects in interface glial cell migration seen in fra[3]/fra[4] embryos. The defects in interface glial cell migration seen in fra[3]/fra[4] embryos are not rescued by expression of fra[Scer\UAS.cKa] under the control of any one of Scer\GAL4[repo], Scer\GAL4[pros.PMG], Scer\GAL4[elav.PU] or Scer\GAL4[Mz605]. (von Hilchen et al., 2010) Expression of fra[Scer\UAS.cKa] under the control of Scer\GAL4[eve.CQ2] rescues dendritic targeting to the midline in fra[3]/fra[4] mutant MN-VO4-6 and MN-VO4/5 neurons. Expression of fra[Scer\UAS.cKa] under the control of Scer\GAL4[eve.CQ2] selectively in MN-LL1 neurons in fra[3]/fra[4] mutant embryos efficiently rescues dendritic targeting to the intermediate neuropile. Moreover, this manipulation leads to a greater proportion of dendritic branches innervating the intermediate neuropile. (Mauss et al., 2009) Expression of fra[Scer\UAS.T:Hsap\MYC] under the control of Scer\GAL4[eg-Mz360] cell-autonomously rescues the EW guidance defects of fra[3]/fra[4] embryos. Expression of fra[Scer\UAS.T:Ivir\HA] under the control of Scer\GAL4[eg-Mz360] cell-autonomously rescues the EW guidance defects of fra[3]/fra[4] embryos. (Garbe et al., 2007) Expression of fra^Scer\UAS.cKa under the control of Scer\GAL4^15J2 does not rescue the dMP2 axonal phenotype of fra³/fra⁴ embryos. Expression of fra^Scer\UAS.cKa under the control of Scer\GAL4⁶⁰⁵ does rescue the dMP2 axonal phenotype of fra³/fra⁴ embryos. (Hiramoto et al., 2000) Scer\GAL4¹⁴⁰⁷ induced expression of fra^Scer\UAS.cKa in fra³/fra⁴ embryos rescues the commissure phenotype, commissures form normally in abdominal segments A1-A7. ISN motor axons also innervate their targets at near wild type levels. (Kolodziej et al., 1996)
Stocks ( 1 )
Bloomington	8743 w^*; P{FRT(w^hs)}G13 fra⁴/CyO, P{lacZ-un3}276
Notes on Origin
Discoverer

External Crossreferences & Linkouts
Other Crossreferences

Linkouts

Synonyms & Secondary IDs ( 2 )
Reported As
Symbol Synonym	fra4 (Dorsten et al., 2007) fra⁴ (Joly et al., 2007, von Hilchen et al., 2010, Andrews et al., 2008, Morikawa et al., 2011, Garbe et al., 2007, Mauss et al., 2009, Yang et al., 2009, Kuzina et al., 2011, Dorsten et al., 2007)
Name Synonym
Secondary FlyBase IDs

References ( 18 )
Research paper	Kuzina et al., 2011, Development 138(9): 1839--1849 How Notch establishes longitudinal axon connections between successive segments of the Drosophila CNS. [FBrf0213493] Morikawa et al., 2011, Proc. Natl. Acad. Sci. U.S.A. 108(48): 19389--19394 Different levels of the Tripartite motif protein, Anomalies in sensory axon patterning (Asap), regulate distinct axonal projections of Drosophila sensory neurons. [FBrf0216734] von Hilchen et al., 2010, Development 137(8): 1251--1262 Netrins guide migration of distinct glial cells in the Drosophila embryo. [FBrf0210391] Mauss et al., 2009, PLoS Biol. 7(9): e1000200 Midline signalling systems direct the formation of a neural map by dendritic targeting in the Drosophila motor system. [FBrf0208790] Yang et al., 2009, Science 324(5929): 944--947 A frazzled/DCC-dependent transcriptional switch regulates midline axon guidance. [FBrf0207948] Andrews et al., 2008, Development 135(23): 3839--3848 Dscam guides embryonic axons by Netrin-dependent and -independent functions. [FBrf0206236] Dorsten et al., 2007, Dev. Biol. 308(1): 120--132 Frazzled regulation of myosin II activity in the Drosophila embryonic CNS. [FBrf0200818] Garbe et al., 2007, Development 134(24): 4325--4334 Cytoplasmic domain requirements for Frazzled-mediated attractive axon turning at the Drosophila midline. [FBrf0200520] Joly et al., 2007, Dev. Biol. 301(2): 542--554 Engrailed controls the organization of the ventral nerve cord through frazzled regulation. [FBrf0194180] Forsthoefel et al., 2005, Development 132(8): 1983--1994 The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor Frazzled in Drosophila. [FBrf0183931] Kolesnikov and Beckendorf, 2005, Dev. Biol. 284(1): 102--111 NETRIN and SLIT guide salivary gland migration. [FBrf0187388] Kim et al., 2002, Dev. Biol. 249(2): 367--381 Constitutively active myosin light chain kinase alters axon guidance decisions in Drosophila embryos. [FBrf0151882] Ratnaparkhi et al., 2002, J. Neurosci. 22(11): 4499--4508 Altered levels of gq activity modulate axonal pathfinding in Drosophila. [FBrf0149078] Keleman and Dickson, 2001, Neuron 32(4): 605--617 Short- and long-range repulsion by the Drosophila Unc5 Netrin receptor. [FBrf0141688] Gong et al., 1999, Development 126(7): 1451--1456 The Netrin receptor Frazzled is required in the target for establishment of retinal projections in the Drosophila visual system. [FBrf0108188] Winberg et al., 1998, Cell 93(4): 581--591 Genetic analysis of the mechanisms controlling target selection: complementary and combinatorial functions of netrins, semaphorins, and IgCAMs. [FBrf0102605] Kolodziej et al., 1996, Cell 87(2): 197--204 frazzled encodes a Drosophila member of the DCC immunoglobulin subfamily and is required for CNS and motor axon guidance. [FBrf0090650]
Letter	Hiramoto et al., 2000, Nature 406(6798): 886--889 The Drosophila Netrin receptor Frazzled guides axons by controlling Netrin distribution. [FBrf0129858]

Allele Dmel\fra4

Allele Dmel\fra⁴