title: Genetic screens for Caenorhabditis elegans mutants defective in left/right asymmetric neuronal fate specification.
abstract: We describe here the results of genetic screens for Caenorhabditis elegans mutants in which a single neuronal fate decision is inappropriately executed. In wild-type animals, the two morphologically bilaterally symmetric gustatory neurons ASE left (ASEL) and ASE right (ASER) undergo a left/right asymmetric diversification in cell fate, manifested by the differential expression of a class of putative chemoreceptors and neuropeptides. Using single cell-specific gfp reporters and screening through a total of almost 120,000 haploid genomes, we isolated 161 mutants that define at least six different classes of mutant phenotypes in which ASEL/R fate is disrupted. Each mutant phenotypic class encompasses one to nine different complementation groups. Besides many alleles of 10 previously described genes, we have identified at least 16 novel "lsy" genes ("laterally symmetric"). Among mutations in known genes, we retrieved four alleles of the miRNA lsy-6 and a gain-of-function mutation in the 3'-UTR of a target of lsy-6, the cog-1 homeobox gene. Using newly found temperature-sensitive alleles of cog-1, we determined that a bistable feedback loop controlling ASEL vs. ASER fate, of which cog-1 is a component, is only transiently required to initiate but not to maintain ASEL and ASER fate. Taken together, our mutant screens identified a broad catalog of genes whose molecular characterization is expected to provide more insight into the complex genetic architecture of a left/right asymmetric neuronal cell fate decision.
authors: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University Medical Center, 701 W. 168th Street, New York, NY 10032, USA.
authors: Sumeet
authors: S
authors: Sarin
authors: M Maggie
authors: MM
authors: O'Meara
authors: Eileen B
authors: EB
authors: Flowers
authors: Celia
authors: C
authors: Antonio
authors: Richard J
authors: RJ
authors: Poole
authors: Dominic
authors: D
authors: Didiano
authors: Robert J
authors: RJ
authors: Johnston
authors: Sarah
authors: S
authors: Chang
authors: Surinder
authors: S
authors: Narula
authors: Oliver
authors: O
authors: Hobert
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D019521:Body Patterning / Q000235:genetics; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics* / Q000254:growth & development*; D016923:Cell Death / Q000235:genetics; D002874:Chromosome Mapping; D017931:DNA Primers / Q000235:genetics; D018509:DNA, Helminth / Q000235:genetics; D017238:Genes, Helminth; D005801:Genes, Homeobox; D017930:Genes, Reporter; D007473:Ion Channels / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D012689:Sequence Homology, Nucleic Acid
chemical_list: D017931:DNA Primers; D018509:DNA, Helminth; D007473:Ion Channels
references: Dev Biol. 2001 Aug 1;236(1):165-80
references: 11456452
references: Dev Biol. 2002 Dec 15;252(2):202-13
references: 12482710
references: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11032-8
references: 11572964
references: Genome Res. 2002 Jul;12(7):1100-5
references: 12097347
references: Nat Rev Neurosci. 2002 Aug;3(8):629-40
references: 12154364
references: Development. 2003 Apr;130(7):1215-24
references: 12588839
references: Genes Dev. 2003 Sep 1;17(17):2123-37
references: 12952888
references: Dev Cell. 2003 Oct;5(4):621-33
references: 14536063
references: Nature. 2003 Dec 18;426(6968):845-9
references: 14685240
references: Development. 2004 May;131(9):1967-78
references: 15056620
references: Nature. 2004 Aug 12;430(7001):785-9
references: 15306811
references: RNA. 2004 Sep;10(9):1309-22
references: 15317971
references: Genetics. 2004 Sep;168(1):489-502
references: 15454559
references: Genetics. 1974 May;77(1):71-94
references: 4366476
references: Dev Biol. 1983 Nov;100(1):64-119
references: 6684600
references: Cell. 1987 Dec 24;51(6):1071-8
references: 3690660
references: Neuron. 1991 Nov;7(5):729-42
references: 1660283
references: Cell. 1993 Nov 19;75(4):641-52
references: 8242740
references: Genetics. 1993 Nov;135(3):741-53
references: 7904971
references: Science. 1994 Feb 11;263(5148):802-5
references: 8303295
references: Cell. 1996 Jul 26;86(2):201-8
references: 8706125
references: Neuron. 1996 Oct;17(4):695-706
references: 8893026
references: Neuron. 1996 Oct;17(4):707-18
references: 8893027
references: Cell. 1999 Nov 12;99(4):387-98
references: 10571181
references: Development. 2000 Feb;127(4):713-23
references: 10648230
references: Nature. 2001 Apr 5;410(6829):694-8
references: 11287956
references: Cell. 2001 Mar 23;104(6):861-73
references: 11290324
references: Nat Genet. 2001 Jun;28(2):160-4
references: 11381264
references: Development. 1996 Nov;122(11):3509-18
references: 8951066
references: Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3384-7
references: 9096403
references: Genetics. 1997 May;146(1):149-64
references: 9136008
references: Development. 1997 May;124(9):1699-709
references: 9165118
references: Cell. 1998 May 15;93(4):519-29
references: 9604928
references: Cell. 1999 Jan 22;96(2):211-24
references: 9988216
references: Cell. 1999 Feb 19;96(4):587-97
references: 10052460
references: Development. 1999 Apr;126(7):1547-62
references: 10068647
references: Dev Cell. 2005 Jun;8(6):867-79
references: 15935776
references: Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12449-54
references: 16099833
references: BMC Genomics. 2005;6:118
references: 16156901
references: Development. 2005 Dec;132(24):5451-60
references: 16291785
references: Genetics. 2006 May;173(1):131-49
references: 16547101
references: Nat Rev Neurosci. 2006 Aug;7(8):655-62
references: 16858393
references: Development. 2006 Sep;133(17):3317-28
references: 16887832
references: Nat Struct Mol Biol. 2006 Sep;13(9):849-51
references: 16921378
references: Curr Biol. 2006 Dec 5;16(23):2279-92
references: 17141609
references: Development. 2007 Jan;134(1):19-29
references: 17138663
references: Cold Spring Harb Symp Quant Biol. 2006;71:181-8
references: 17381295
references: Trends Genet. 2007 May;23(5):243-9
references: 17368621
references: Dev Biol. 2007 May 15;305(2):551-63
references: 17412319
references: Genes Dev. 2007 Jul 1;21(13):1653-74
references: 17606643
references: Cell. 2001 Jul 13;106(1):23-34
references: 11461699