title: Functional transcriptomic analysis of the role of MAB-5/Hox in Q neuroblast migration in Caenorhabditis elegans.
abstract: BACKGROUND
  Directed cell migration is a fundamental process in normal development and in tumor metastasis. In C. elegans the MAB-5/Hox transcription factor is a determinant of posterior migration of the Q neuroblast descendants. In this work, mab-5 transcriptional targets that control Q descendant migration are identified by comparing RNA-seq profiles in wild type and mab-5 mutant backgrounds.
  
  
  RESULTS
  Transcriptome profiling is a widely-used and potent tool to identify genes involved in developmental and pathological processes, and is most informative when RNA can be isolated from individual cell or tissue types. Cell-specific RNA samples can be difficult to obtain from invertebrate model organisms such as Drosophila and C. elegans. Here we test the utility of combining a whole organism RNA-seq approach with mab-5 loss and gain-of-function mutants and functional validation using RNAi to identify genes regulated by MAB-5 to control Q descendant migration. We identified 22 genes whose expression was controlled by mab-5 and that controlled Q descendant migration. Genes regulated by mab-5 were enriched for secreted and transmembrane molecules involved in basement membrane interaction and modification, and some affected Q descendant migration.
  
  
  CONCLUSIONS
  Our results indicate that a whole-organism RNA-seq approach, when combined with mutant analysis and functional validation, can be a powerful method to identify genes involved in a specific developmental process, in this case Q descendant posterior migration. These genes could act either autonomously in the Q cells, or non-autonomously in other cells that express MAB-5. The identities of the genes regulated by MAB-5 indicate that MAB-5 acts by modifying interactions with the basement membrane, resulting in posterior versus anterior migration.
authors: Department of Molecular Biosciences, Programs in Genetics and Molecular, Cellular, and Developmental Biology, The University of Kansas, 1200 Sunnyside Avenue, Lawrence, KS 66045, USA.
authors: Joel V
authors: JV
authors: Tamayo
authors: Mahekta
authors: M
authors: Gujar
authors: Stuart J
authors: SJ
authors: Macdonald
authors: Erik A
authors: EA
authors: Lundquist
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D019070:Cell Lineage; D002465:Cell Movement / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D058953:Neural Stem Cells; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D018398:Homeodomain Proteins; C081538:Mab-5 protein, C elegans; D014157:Transcription Factors
references: Dev Biol. 1977 Mar;56(1):110-56
references: 838129
references: Nature. 2004 Jul 15;430(6997):317-22
references: 15220933
references: Development. 2008 Aug;135(16):2747-2756
references: 18614580
references: Nature. 1992 Jan 16;355(6357):255-8
references: 1346230
references: PLoS One. 2011;6(5):e20085
references: 21647448
references: Development. 2000 Nov;127(21):4655-68
references: 11023868
references: Development. 1999 Jan;126(1):37-49
references: 9834184
references: Development. 2002 Nov;129(22):5255-68
references: 12399316
references: Genome Biol. 2011;12(3):R22
references: 21410973
references: Small GTPases. 2010 Jul;1(1):44-61
references: 21686119
references: Dev Cell. 2003 Jul;5(1):21-31
references: 12852849
references: Biochemistry. 1999 Nov 2;38(44):14549-58
references: 10545177
references: Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2721-6
references: 17301221
references: Cell. 1994 Aug 26;78(4):603-15
references: 7915199
references: WormBook. 2005 Jun 25;:1-17
references: 18050402
references: Dev Biol. 2011 Sep 15;357(2):380-91
references: 21784067
references: Nat Cell Biol. 2011 Jun;13(6):641-51
references: 21572423
references: Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16246-51
references: 22991463
references: Science. 1983 Jul 1;221(4605):61-3
references: 6857263
references: Genome Biol. 2009;10(3):R25
references: 19261174
references: Development. 1998 Mar;125(6):1083-93
references: 9463355
references: Nat Biotechnol. 2010 May;28(5):511-5
references: 20436464
references: Genome Biol. 2007;8(7):R135
references: 17612406
references: Development. 1996 May;122(5):1651-61
references: 8625851
references: Nat Protoc. 2009;4(1):44-57
references: 19131956
references: Development. 2011 Jul;138(14):2915-24
references: 21653614
references: Bioinformatics. 2011 Sep 1;27(17):2325-9
references: 21697122
references: Genetics. 2012 Dec;192(4):1373-88
references: 23051647
references: Nat Protoc. 2012 Mar 01;7(3):562-78
references: 22383036
references: Development. 2009 May;136(9):1433-42
references: 19297413
references: Dev Biol. 2007 Aug 1;308(1):187-95
references: 17573066
references: Cell. 2005 Jun 17;121(6):951-62
references: 15960981
references: Development. 2005 Mar;132(6):1413-28
references: 15750187
references: Development. 1996 Oct;122(10):3117-31
references: 8898225
references: Nature. 2003 Jan 16;421(6920):231-7
references: 12529635
references: Nat Rev Genet. 2009 Jan;10(1):57-63
references: 19015660
references: Genome Res. 2011 Feb;21(2):245-54
references: 21177963
references: Bioinformatics. 2009 May 1;25(9):1105-11
references: 19289445
references: Curr Opin Cell Biol. 2010 Oct;22(5):640-50
references: 20832275
references: Dev Biol. 1981 Mar;82(2):358-70
references: 7227647
references: Development. 2001 Feb;128(4):581-90
references: 11171341
references: Development. 2006 Feb;133(4):641-50
references: 16421192
references: Cell. 1999 Jul 9;98(1):25-36
references: 10412978
references: Dev Cell. 2010 Jul 20;19(1):13-26
references: 20643347
references: Dev Biol. 2008 Dec 15;324(2):245-57
references: 18840424
references: Nucleic Acids Res. 2009 Jan;37(1):1-13
references: 19033363
references: Genes Dev. 1993 Sep;7(9):1714-24
references: 8103754
references: Cell. 1986 Aug 1;46(3):477-87
references: 3731276
references: Dev Biol. 2012 Jan 15;361(2):338-48
references: 22074987