title: Hoxd and Gli3 interactions modulate digit number in the amniote limb.
abstract: During limb development, Sonic hedgehog (SHH) and HOX proteins are considered among the most important factors regulating digit number and identity. SHH signaling prevents the processing of GLI3 into a short form that functions as a strong transcriptional repressor. Gli3 mutant limbs are characterized by a severe polydactyly and associated ectopic anterior expression of 5'Hoxd genes. To genetically determine the involvement of 5'Hoxd genes in the polydactyly of Gli3 mutants, we have generated a compound mutant that simultaneously removes the three most 5'-located Hoxd genes and Gli3. Remarkably, the limbs that form in the absence of all four of these genes show the most severe polydactyly so far reported in the mouse. The analysis of gene expression performed in compound mutants allows us to propose that the increase in the number of digits is mediated by the gain in function of Hoxd10 and Hoxd9. Our results also support the notion that an adequate balance between positive and negative effects of different Hoxd genes is required for pentadactyly.
authors: Departamento de Anatomía y Biología Celular, Universidad de Cantabria, 39011, Santander, Spain.
authors: Rushikesh
authors: R
authors: Sheth
authors: M Félix
authors: MF
authors: Bastida
authors: Marian
authors: M
authors: Ros
mesh_terms: D000818:Animals; D005121:Extremities / Q000196:embryology* / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017689:Polydactyly / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000074290:Zinc Finger Protein Gli3
chemical_list: C465571:Gli3 protein, mouse; D018398:Homeodomain Proteins; C065404:Hoxc9 protein, mouse; C490944:Hoxd10 protein, mouse; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D000074290:Zinc Finger Protein Gli3