title: A function for all posterior Hoxd genes during digit development?
abstract: BACKGROUND
  Four posterior Hoxd genes, from Hoxd13 to Hoxd10, are collectively regulated during the development of tetrapod digits. Besides the well-documented role of Hoxd13, the function of the neighboring genes has been difficult to evaluate due to the close genetic linkage and potential regulatory interferences. We used a combination of five small nested deletions in cis, involving from two to four consecutive genes of the Hoxd13 to Hoxd9 loci, in mice, to evaluate their combined functional importance.
  
  
  RESULTS
  We show that deletions leading to a gain of function of Hoxd13, via regulatory re-allocation, generate abnormal phenotypes, in agreement with the dominant negative role of this gene. We also show that Hoxd10, Hoxd11, and Hoxd12 all seem to play a genuine role in digit development, though less compelling than that of Hoxd13. In contrast, the nearby Hoxd9 contributed no measurable function in digits.
  
  
  CONCLUSIONS
  We conclude that a slight and transient deregulation of Hoxd13 expression can readily affect the relative lengths of limb segments and that all posterior Hoxd genes likely contribute to the final limb morphology. We discuss the difficulty to clearly assess the functional share of individual genes within such a gene family, where closely located neighbors, coding for homologous proteins, are regulated by a unique circuitry and all contribute to shape the distal parts of our appendages.
authors.affiliation: National Research Centre Frontiers in Genetics, School of Life Sciences, Ecole Polytechnique Fédérale, Lausanne, Switzerland.
authors.forename: Saskia
authors.initials: S
authors.lastname: Delpretti
authors.forename: Jozsef
authors.initials: J
authors.lastname: Zakany
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; C490939:Hoxd11 protein, mouse; C490943:Hoxd12 protein, mouse; C084118:Hoxd13 protein, mouse; D014157:Transcription Factors