Homeotic Transformation of Cervical Vertebrae in Hoxa-4 Mutant Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Dec 20

PMID 7809093

Citations 43

Authors

G S Horan

K Wu

D J Wolgemuth

R R Behringer

Affiliations

Soon will be listed here.

Abstract

Hoxa-4 (previously known as Hox-1.4) is a mouse homeobox-containing gene that is expressed in the presumptive hindbrain and spinal cord, prevertebrae, and other tissues during embryogenesis. To understand the role of Hoxa-4 during development, we generated Hoxa-4 mutant mice. Homozygous mutants were viable and fertile. Analysis of neonatal skeletons revealed the development of ribs on the seventh cervical vertebra at variable penetrance and expressivity. A low frequency of alterations in sternal morphogenesis was also observed. In addition, we analyzed the skeletons of transgenic mice that overexpress Hoxa-4 and found that the formation of the small rib anlagen that often develop on the seventh cervical vertebra was suppressed. Analysis of adult homozygous mutant skeletons revealed that the dorsal process normally associated with the second cervical vertebra was also found on the third cervical vertebra. These results demonstrate that Hoxa-4 plays a role in conferring positional information along the anteroposterior axis to specify the identity of the third and the seventh cervical vertebrae.

Citing Articles

Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos.

Hung Y, Lin W, Wang Y, Kuo W, Chen Y, Fann M Commun Biol. 2024; 7(1):1669.

PMID: 39702818 PMC: 11659552. DOI: 10.1038/s42003-024-07342-8.

Homeotic and nonhomeotic patterns in the tetrapod vertebral formula.

Cerbus R, Hiratani I, Kawaguchi K Proc Natl Acad Sci U S A. 2024; 121(47):e2411421121.

PMID: 39527744 PMC: 11588047. DOI: 10.1073/pnas.2411421121.

Breaking the constraint on the number of cervical vertebrae in mammals: On homeotic transformations in lorises and pottos.

Galis F, Van Dooren T, van der Geer A Evol Dev. 2022; 24(6):196-210.

PMID: 36316803 PMC: 9788262. DOI: 10.1111/ede.12424.

HOX-Gene Cluster Organization and Genome Duplications in Fishes and Mammals: Transcript Variant Distribution along the Anterior-Posterior Axis.

Ozernyuk N, Schepetov D Int J Mol Sci. 2022; 23(17).

PMID: 36077385 PMC: 9456325. DOI: 10.3390/ijms23179990.

compensates for in mice in the amino-terminal acetylation pathway.

Kweon H, Lee M, Dorfel M, Seo S, Gottlieb L, Papazyan T Elife. 2021; 10.

PMID: 34355692 PMC: 8376253. DOI: 10.7554/eLife.65952.

References

Kochhar D . Limb development in mouse embryos. I. Analysis of teratogenic effects of retinoic acid. Teratology. 1973; 7(3):289-98. DOI: 10.1002/tera.1420070310. View

Kostic D, Capecchi M . Targeted disruptions of the murine Hoxa-4 and Hoxa-6 genes result in homeotic transformations of components of the vertebral column. Mech Dev. 1994; 46(3):231-47. DOI: 10.1016/0925-4773(94)90073-6. View

Cathala G, Savouret J, Mendez B, West B, Karin M, Martial J . A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983; 2(4):329-35. DOI: 10.1089/dna.1983.2.329. View

Sanchez-Herrero E, Vernos I, Marco R, Morata G . Genetic organization of Drosophila bithorax complex. Nature. 1985; 313(5998):108-13. DOI: 10.1038/313108a0. View

Ponzetto C, Wolgemuth D . Haploid expression of a unique c-abl transcript in the mouse male germ line. Mol Cell Biol. 1985; 5(7):1791-4. PMC: 367300. DOI: 10.1128/mcb.5.7.1791-1794.1985. View

Wolgemuth D, Engelmyer E, Duggal R, Mutter G, Ponzetto C, Viviano C . Isolation of a mouse cDNA coding for a developmentally regulated, testis-specific transcript containing homeo box homology. EMBO J. 1986; 5(6):1229-35. PMC: 1166932. DOI: 10.1002/j.1460-2075.1986.tb04351.x. View

Wolgemuth D, Viviano C, Frohman M, Joyner A, Martin G . Differential expression of the mouse homeobox-containing gene Hox-1.4 during male germ cell differentiation and embryonic development. Proc Natl Acad Sci U S A. 1987; 84(16):5813-7. PMC: 298953. DOI: 10.1073/pnas.84.16.5813. View

Mansour S, Thomas K, Capecchi M . Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: a general strategy for targeting mutations to non-selectable genes. Nature. 1988; 336(6197):348-52. DOI: 10.1038/336348a0. View

Wolgemuth D, Behringer R, Mostoller M, Brinster R, Palmiter R . Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development. Nature. 1989; 337(6206):464-7. DOI: 10.1038/337464a0. View

10.

Scott M, Tamkun J, Hartzell 3rd G . The structure and function of the homeodomain. Biochim Biophys Acta. 1989; 989(1):25-48. DOI: 10.1016/0304-419x(89)90033-4. View

11.

Gaunt S, Krumlauf R, Duboule D . Mouse homeo-genes within a subfamily, Hox-1.4, -2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage- and tissue-dependent differences in their regulation. Development. 1989; 107(1):131-41. DOI: 10.1242/dev.107.1.131. View

12.

McMahon A, Bradley A . The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. Cell. 1990; 62(6):1073-85. DOI: 10.1016/0092-8674(90)90385-r. View

13.

Soriano P, Montgomery C, Geske R, Bradley A . Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991; 64(4):693-702. DOI: 10.1016/0092-8674(91)90499-o. View

14.

Chisaka O, Capecchi M . Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature. 1991; 350(6318):473-9. DOI: 10.1038/350473a0. View

15.

Lufkin T, Dierich A, Lemeur M, Mark M, Chambon P . Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell. 1991; 66(6):1105-19. DOI: 10.1016/0092-8674(91)90034-v. View

16.

McGinnis W, Krumlauf R . Homeobox genes and axial patterning. Cell. 1992; 68(2):283-302. DOI: 10.1016/0092-8674(92)90471-n. View

17.

Scott M . Vertebrate homeobox gene nomenclature. Cell. 1992; 71(4):551-3. DOI: 10.1016/0092-8674(92)90588-4. View

18.

Kessel M . Respecification of vertebral identities by retinoic acid. Development. 1992; 115(2):487-501. DOI: 10.1242/dev.115.2.487. View

19.

Watrin F, Wolgemuth D . Conservation and divergence of patterns of expression and lineage-specific transcripts in orthologues and paralogues of the mouse Hox-1.4 gene. Dev Biol. 1993; 156(1):136-45. DOI: 10.1006/dbio.1993.1064. View

20.

Ramirez-Solis R, Zheng H, Whiting J, Krumlauf R, Bradley A . Hoxb-4 (Hox-2.6) mutant mice show homeotic transformation of a cervical vertebra and defects in the closure of the sternal rudiments. Cell. 1993; 73(2):279-94. DOI: 10.1016/0092-8674(93)90229-j. View