title: Neogenin regulates Sonic Hedgehog pathway activity during digit patterning.
abstract: BACKGROUND
  Digit patterning integrates signaling by the Sonic Hedgehog (SHH), fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) pathways. GLI3, a component of the SHH pathway, is a major regulator of digit number and identity. Neogenin (encoded by Neo1) is a cell surface protein that serves to transduce signals from several ligands, including BMPs, in various developmental contexts. Although neogenin is implicated in BMP signaling, it has not been linked to SHH signaling and its role in digit patterning is unknown.
  
  
  RESULTS
  We report that Neo1 mutant mice have preaxial polydactyly with low penetrance. Expression of SHH target genes, but not BMP target genes, is altered in Neo1 mutant limb buds. Analysis of mice carrying mutations in both Neo1 and Gli3 reveals that, although neogenin plays a role in constraint of digit numbers, suppressing polydactyly, it is also required for the severe polydactyly caused by loss of GLI3. Furthermore, embryo fibroblasts from Neo1 mutant mice are sensitized to SHH pathway activation in vitro.
  
  
  CONCLUSIONS
  Our findings indicate that neogenin regulates SHH signaling in the limb bud to achieve proper digit patterning.
authors.affiliation: Department of Developmental and Regenerative Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Mingi
authors.initials: M
authors.lastname: Hong
authors.forename: Karen A
authors.initials: KA
authors.lastname: Schachter
authors.forename: Guoying
authors.initials: G
authors.lastname: Jiang
authors.forename: Robert S
authors.initials: RS
authors.lastname: Krauss
mesh_terms: D000818:Animals; D019521:Body Patterning; D053823:Hedgehog Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017689:Polydactyly / Q000235:genetics*; D015398:Signal Transduction; D034941:Upper Extremity / Q000196:embryology*; D038062:Upper Extremity Deformities, Congenital / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D000071676:Zinc Finger Protein GLI1; C091279:neogenin