DOI: 10.1242/dev.122.2.449. Functional cooperation between the non-paralogous genes <i>Hoxa-10</i> and <i>Hoxd-11</i> in the developing forelimb and axial skeleton

Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton

10.1242/dev.122.2.449

Crossref journal-article

The Company of Biologists

Development (237)

Abstract

ABSTRACT The Abdominal B-related Hoxa-10 gene displays similar expression patterns in the differentiating forelimbs and hindlimbs of the mouse, with preferential expression around the humeral and femoral cartilages and more diffuse expression in distal regions. We found that a targeted disruption of Hoxa-10 has almost no effect in the forelimbs, while it affects the proximal hindlimb skeleton. The alterations were located along the dorsolateral side of the femur (labium laterale), with an enlargement and distal shift of the third trochanter, a misshapen lateral knee sesamoid, a supernumerary ‘ligament’ connecting these structures and an occasional duplication of the femoral trochlea. Some Hoxa-10−/− mutant mice developed severe degenerative alterations of the knee articulation upon ageing. Viable Hoxa-10/Hoxd-11 double mutant mice were produced by genetic intercrosses. The compound mutation resulted in synergistic forelimb phenotypic alterations, consisting of: (i) an exacerbation of Hoxd-11−/− phenotypic traits in the carpal and digital region, e.g. more pronounced truncations of the ulna styloid, pyramidal and pisiform bones and of some metacarpal and phalangeal bones and (ii) marked alterations in a more proximal region which is nearly unaffected in Hoxd-11−/− single mutants; the entire radius and ulna were truncated and thickened, with deformations of the ulna proximal extremity. Thus, functional redundancy can occur even between non-paralogous Abdominal B-related Hox genes. The double Hoxa-10/Hoxd-11 mutation also conferred full penetrance to the sacral and caudal vertebrae transforma-tions which are ∽50% penetrant in Hoxd-11−/− single mutants, revealing that functional cooperation can also occur between non-paralogous Hox gene products in axial skeleton patterning.

Bibliography

Favier, B., Rijli, F. M., Fromental-Ramain, C., Fraulob, V., Chambon, P., & DollÃ©, P. (1996). Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton. Development, 122(2), 449â460.

Authors 6

Bertrand Favier (first)
Filippo M. Rijli (additional)
Catherine Fromental-Ramain (additional)
Valérie Fraulob (additional)
Pierre Chambon (additional)
Pascal Dollé (additional)

References 24 Referenced 129

{'volume-title': 'Anatomie Comparée des Mammifères Domestiques', 'year': '1986', 'author': 'Barone', 'key': '2025021322190277800_DEVELOP_122_2_449C1'} / Anatomie Comparée des Mammifères Domestiques by Barone (1986)
10.1242/dev.120.8.2187 / Development / Axial homeosis and appendicular skeleton defects in mice with a targeted disruption of Hoxd-11 by Davis (1994)
10.1038/375791a0 / Nature / Absence of radius and ulna in mice lacking Hoxa-11 and Hoxd-11 by Davis (1995)
10.1038/342767a0 / Nature / Coordinate expression of the murine Hox-5 complex homeobox-containing genes during limb pattern formation by Dollé (1989)
10.1016/0092-8674(93)90378-4 / Cell / Disruption of the Hoxd-13 gene induces localized heterochrony leading to mice with neotenic limbs by Dollé (1993)
10.1016/S0959-437X(05)80072-3 / Curr. Opin. Genet. Dev / Patterning in the vertebrate limb by Duboule (1991)
10.1002/bies.950140606 / BioEssays / The vertebrate limb: a model system to study the HOX/HOM gene network during development and evolution by Duboule (1992)
10.1002/j.1460-2075.1989.tb03534.x / EMBO J / The structural and functional organization of the murine HOX gene family ressembles that of Drosophila homeotic genes by Duboule (1989)
10.1016/0168-9525(94)90132-5 / Trends Genet / Colinearity and functional hierarchy among genes of the homeotic complexes by Duboule (1994)
10.1073/pnas.92.1.310 / Proc. Natl. Acad. Sci. USA / Axial skeleton homeosis and forelimb malformations in Hoxd-11 mutant mice by Favier (1995)
10.1242/dev.122.2.461 / Development / Specific and redundant functions of the paralogous Hoxa-9 and Hoxd-9 genes in forelimb and axial skeleton patterning by Fromental-Ramain (1996)
10.1006/dbio.1993.1145 / Dev. Biol / The establishment of murine Hox-1 expression domains during patterning of the limb by Haack (1993)
{'key': '2025021322190277800_DEVELOP_122_2_449C13', 'first-page': '133', 'article-title': 'The role of movement and tissue interactions in the development and growth of bone and secondary cartilage in the clavicle of the embryonic chick', 'volume': '93', 'author': 'Hall', 'year': '1986', 'journal-title': 'J. Embryol. Exp. Morph'} / J. Embryol. Exp. Morph / The role of movement and tissue interactions in the development and growth of bone and secondary cartilage in the clavicle of the embryonic chick by Hall (1986)
{'key': '2025021322190277800_DEVELOP_122_2_449C14', 'article-title': 'Evolutionary developmental biology of the tetrapod limb', 'volume-title': 'Development', 'author': 'Hinchliffe', 'year': '1994'} / Development / Evolutionary developmental biology of the tetrapod limb by Hinchliffe (1994)
10.1002/j.1460-2075.1991.tb07764.x / EMBO J / Murine genes related to the Drosophila Abd B homeotic gene are sequentially expressed during development of the posterior part of the body by Izpisúa-Belmonte (1991)
10.1016/0092-8674(91)90574-I / Cell / Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid by Kessel (1991)
10.1016/0925-4773(94)90043-4 / Mech. Dev / The murine HOXC cluster contains five neighboring AbdB-related Hox genes that show unique spatially coordinated expression in posterior embryonic subregions by Peterson (1994)
{'volume-title': 'A Color Atlas of the Anatomy of Small Laboratory Animals. 2: Rat, Mouse, Hamster', 'year': '1992', 'author': 'Popesko', 'key': '2025021322190277800_DEVELOP_122_2_449C18'} / A Color Atlas of the Anatomy of Small Laboratory Animals. 2: Rat, Mouse, Hamster by Popesko (1992)
10.1101/gad.9.1.108 / Genes Dev / Genetic interaction between Hoxb-5 and Hoxb-6 is revealed by nonallelic noncomplementation by Rancourt (1995)
10.1073/pnas.92.18.8185 / Proc. Natl. Acad. Sci. USA / Cryptorchidism and homeotic transformations of spinal nerves and vertebrae in Hoxa-10 mutant mice by Rijli (1995)
10.1038/374460a0 / Nature / Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice by Satokata (1995)
{'key': '2025021322190277800_DEVELOP_122_2_449C22', 'first-page': '319', 'article-title': 'A morphogenetic approach to the the origin and basic organisation of the tetrapod limb', 'volume': '20', 'author': 'Shubin', 'year': '1986', 'journal-title': 'Evol. Biol'} / Evol. Biol / A morphogenetic approach to the the origin and basic organisation of the tetrapod limb by Shubin (1986)
10.1101/gad.7.12a.2318 / Genes Dev / Homeotic transformations and limb defects in Hoxa-11 mutant mice by Small (1993)
10.1038/375678a0 / Nature / Hox gene expression in teleost fins and the origin of vertebrate digits by Sordino (1995)

Dates

Type	When
Created	4 years, 4 months ago (April 25, 2021, 10:31 p.m.)
Deposited	6 months, 2 weeks ago (Feb. 13, 2025, 5:19 p.m.)
Indexed	6 months, 2 weeks ago (Feb. 14, 2025, 12:32 a.m.)
Issued	29 years, 6 months ago (Feb. 1, 1996)
Published	29 years, 6 months ago (Feb. 1, 1996)
Published Online	29 years, 6 months ago (Feb. 1, 1996)
Published Print	29 years, 6 months ago (Feb. 1, 1996)

Funders 0

None

BibTeX

@article{Favier_1996, title={Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton}, volume={122}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.122.2.449}, DOI={10.1242/dev.122.2.449}, number={2}, journal={Development}, publisher={The Company of Biologists}, author={Favier, Bertrand and Rijli, Filippo M. and Fromental-Ramain, Catherine and Fraulob, Valérie and Chambon, Pierre and Dollé, Pascal}, year={1996}, month=feb, pages={449–460} }

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  "abstract": "<jats:title>ABSTRACT</jats:title>\n               <jats:p>The Abdominal B-related Hoxa-10 gene displays similar expression patterns in the differentiating forelimbs and hindlimbs of the mouse, with preferential expression around the humeral and femoral cartilages and more diffuse expression in distal regions. We found that a targeted disruption of Hoxa-10 has almost no effect in the forelimbs, while it affects the proximal hindlimb skeleton. The alterations were located along the dorsolateral side of the femur (labium laterale), with an enlargement and distal shift of the third trochanter, a misshapen lateral knee sesamoid, a supernumerary \u2018ligament\u2019 connecting these structures and an occasional duplication of the femoral trochlea. Some Hoxa-10\u2212/\u2212 mutant mice developed severe degenerative alterations of the knee articulation upon ageing. Viable Hoxa-10/Hoxd-11 double mutant mice were produced by genetic intercrosses. The compound mutation resulted in synergistic forelimb phenotypic alterations, consisting of: (i) an exacerbation of Hoxd-11\u2212/\u2212 phenotypic traits in the carpal and digital region, e.g. more pronounced truncations of the ulna styloid, pyramidal and pisiform bones and of some metacarpal and phalangeal bones and (ii) marked alterations in a more proximal region which is nearly unaffected in Hoxd-11\u2212/\u2212 single mutants; the entire radius and ulna were truncated and thickened, with deformations of the ulna proximal extremity. Thus, functional redundancy can occur even between non-paralogous Abdominal B-related Hox genes. The double Hoxa-10/Hoxd-11 mutation also conferred full penetrance to the sacral and caudal vertebrae transforma-tions which are \u223d50% penetrant in Hoxd-11\u2212/\u2212 single mutants, revealing that functional cooperation can also occur between non-paralogous Hox gene products in axial skeleton patterning.</jats:p>",
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    "timestamp": 1739485176000
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  "resource": {
    "primary": {
      "URL": "https://journals.biologists.com/dev/article/122/2/449/38934/Functional-cooperation-between-the-non-paralogous"
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}