Abstract
The ancestral role of the Hox gene family is specifying morphogenetic differences along the main body axis. In vertebrates, HoxD genes were also co-opted along with the emergence of novel structures such as limbs and genitalia. We propose that these functional recruitments relied on the appearance, or implementation, of regulatory sequences outside of the complex. Whereas transgenic human and murine HOXD clusters could function during axial patterning, in mice they were not expressed outside the trunk. Accordingly, deletion of the entire cluster abolished axial expression, whereas recently acquired regulatory controls were preserved.
MeSH Terms
Animals
Bone Development/genetics
DNA-Binding Proteins
Embryo, Mammalian/metabolism
Evolution, Molecular
Gene Deletion
Gene Expression Regulation, Developmental
Genes, Reporter
Homeodomain Proteins/genetics,physiology
Humans
In Situ Hybridization
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Models, Genetic
Multigene Family
Mutation
Neoplasm Proteins
Phenotype
Recombination, Genetic
Time Factors
Transcription Factors/genetics
Chemicals
DNA-Binding Proteins
HOXD13 protein, human
Homeodomain Proteins
Hoxd13 protein, mouse
Hoxd3 protein, mouse
Hoxd4 protein, mouse
Hoxd8 protein, mouse
Hoxd9 protein, mouse
Neoplasm Proteins
Transcription Factors
HOXA4 protein, human
HOXD10 protein, human
HOXD8 protein, human
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Spitz F
Department of Zoology and Animal Biology, University of Geneva, Sciences III, 1211 Geneva 4, Switzerland.
Gonzalez F
Peichel C
Vogt T F
Duboule D
Zákány J
References (31)
31 references, click to expand
-
Hox genes and the making of sphincters.
Nature. 1999 Oct 21;401(6755):761-2
PMID: 10548099
-
Polycomb silencing and the maintenance of stable chromatin states.
Results Probl Cell Differ. 1999;25:205-28
PMID: 10339748
-
Initiation, establishment and maintenance of Hox gene expression patterns in the mouse.
Int J Dev Biol. 1999;43(7):635-50
PMID: 10668974
-
Insertion of disease-causing mutations in BACs by homologous recombination in Escherichia coli.
Nucleic Acids Res. 2000 Sep 1;28(17):E79
PMID: 10954612
-
Targeted inversion of a polar silencer within the HoxD complex re-allocates domains of enhancer sharing.
Nat Genet. 2000 Dec;26(4):451-4
PMID: 11101844
-
Hox-5.1 defines a homeobox-containing gene locus on mouse chromosome 2.
Proc Natl Acad Sci U S A. 1988 Jul;85(13):4760-4
PMID: 2898782
-
Region-specific enhancers near two mammalian homeo box genes define adjacent rostrocaudal domains in the central nervous system.
Genes Dev. 1990 Feb;4(2):180-9
PMID: 1970971
-
Isolation and analysis of embryonic expression of Hox-4.9, a member of the murine labial-like gene family.
Mech Dev. 1992 Jul;38(1):55-67
PMID: 1356009
-
Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting.
Cell. 1993 Jun 18;73(6):1155-64
PMID: 8513499
-
A method for the generation of YAC transgenic mice by pronuclear microinjection.
Nucleic Acids Res. 1993 Oct 11;21(20):4783-7
PMID: 8233827
-
Structure and activity of regulatory elements involved in the activation of the Hoxd-11 gene during late gastrulation.
EMBO J. 1993 Sep;12(9):3539-50
PMID: 7902810
-
Hox genes in vertebrate development.
Cell. 1994 Jul 29;78(2):191-201
PMID: 7913880
-
Hox gene expression in teleost fins and the origin of vertebrate digits.
Nature. 1995 Jun 22;375(6533):678-81
PMID: 7791900
-
Specification of multiple vertebral identities by ectopically expressed Hoxb-8.
Dev Dyn. 1995 Sep;204(1):13-21
PMID: 8563021
-
Analysis of Hox gene expression in the chick limb bud.
Development. 1996 May;122(5):1449-66
PMID: 8625833
-
A mutational analysis of the 5' HoxD genes: dissection of genetic interactions during limb development in the mouse.
Development. 1996 Apr;122(4):1175-85
PMID: 8620844
-
Gene transpositions in the HoxD complex reveal a hierarchy of regulatory controls.
Cell. 1996 Jun 28;85(7):1025-35
PMID: 8674109
-
In vivo targeted mutagenesis of a regulatory element required for positioning the Hoxd-11 and Hoxd-10 expression boundaries.
Genes Dev. 1996 Sep 15;10(18):2326-34
PMID: 8824591
-
Synpolydactyly in mice with a targeted deficiency in the HoxD complex.
Nature. 1996 Nov 7;384(6604):69-71
PMID: 8900279
-
Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1.
Genes Dev. 1997 Jul 15;11(14):1885-95
PMID: 9242495
-
Genetic interactions of Hox genes in limb development: learning from compound mutants.
Curr Opin Genet Dev. 1997 Aug;7(4):481-7
PMID: 9309178
-
Functions of mammalian Polycomb group and trithorax group related genes.
Curr Opin Genet Dev. 1997 Aug;7(4):488-94
PMID: 9309179
-
Regulation of number and size of digits by posterior Hox genes: a dose-dependent mechanism with potential evolutionary implications.
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13695-700
PMID: 9391088
-
Hoxc13 mutant mice lack external hair.
Genes Dev. 1998 Jan 1;12(1):11-20
PMID: 9420327
-
Selectivity, sharing and competitive interactions in the regulation of Hoxb genes.
EMBO J. 1998 Mar 16;17(6):1788-98
PMID: 9501100
-
Genetic analysis of a Hoxd-12 regulatory element reveals global versus local modes of controls in the HoxD complex.
Development. 1998 May;125(9):1669-77
PMID: 9521905
-
A new logic for DNA engineering using recombination in Escherichia coli.
Nat Genet. 1998 Oct;20(2):123-8
PMID: 9771703
-
Rapid modification of bacterial artificial chromosomes by ET-recombination.
Nucleic Acids Res. 1999 Mar 15;27(6):1555-7
PMID: 10037821
-
Hox gene expression in limbs: colinearity by opposite regulatory controls.
Dev Biol. 1999 Apr 1;208(1):157-65
PMID: 10075849
-
Breaking colinearity in the mouse HoxD complex.
Cell. 1999 Apr 30;97(3):407-17
PMID: 10319820
-
Mechanisms of Hox gene colinearity: transposition of the anterior Hoxb1 gene into the posterior HoxD complex.
Genes Dev. 2000 Jan 15;14(2):198-211
PMID: 10652274