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  Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and posterior axis elongation

van den Akker, E., Forlani, S., Chawengsaksophak, K., de Graaff, W., Beck, F., Meyer, B., et al. (2002). Cdx1 and Cdx2 have overlapping functions in anteroposterior patterning and posterior axis elongation. Development, 129(9), 2181-2193. Retrieved from http://dev.biologists.org/content/129/9/2181.full.pdf+html.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-F3DA-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-E576-7
Genre: Journal Article

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van den Akker, E., Author
Forlani, S., Author
Chawengsaksophak, K., Author
de Graaff, W., Author
Beck, F., Author
Meyer, B.1, Author              
Deschamps, J., Author
Affiliations:
1Department of Molecular Cell Biology, MPI for biophysical chemistry, Max Planck Society, ou_578585              

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Free keywords: mouse Cdx genes; Hox genes; anteroposterior patterning; axial elongation
 Abstract: Mouse Cdx and Hox genes presumably evolved from genes on a common ancestor cluster involved in anteroposterior patterning. Drosophila caudal (cad) is involved in specifying the posterior end of the early embryo, and is essential for patterning tissues derived from the most caudal segment, the analia. Two of the three mouse Cdx paralogues, Cdx 1 and Cdx2, are expressed early in a Hox-like manner in the three germ layers. In the nascent paraxial mesoderm, both genes are expressed in cells contributing first to the most rostral, and then to progressively more caudal parts of the vertebral column. Later, expression regresses from the anterior sclerotomes, and is only maintained for Cdx1 in the dorsal part of the somites, and for both genes in the tail bud. Cdx1 null mutants show anterior homeosis of upper cervical and thoracic vertebrae. Cdx2-null embryos die before gastrulation, and Cdx2 heterozygotes display anterior transformations of lower cervical and thoracic vertebrae. We have analysed the genetic interactions between Cdx1 and Cdr2 in compound mutants. Combining mutant alleles for both genes gives rise to anterior homeotic transformations along a more extensive length of the vertebral column than do single mutations. The most severely affected Cdx1 null/Cdx2 heterozygous mice display a posterior shift of their cranio- cervical, cervico-thoracic, thoraco-lumbar, lumbo-sacral and sacro-caudal transitions. The effects of the mutations in Cdx1 and Cdx2 were co-operative in severity, and a more extensive posterior shift of the expression of three Hox genes was observed in double mutants. The alteration in Hox expression boundaries occurred early. We conclude that both Cdx genes cooperate at early stages in instructing the vertebral progenitors all along the axis, at least in part by setting the rostral expression boundaries of Hox genes. In addition, Cdx mutants transiently exhibit alterations in the extent of Hox expression domains in the spinal cord, reminding of the strong effects of overexpressing Cdx genes on Hox gene expression in the neurectoderm. Phenotypical alterations in the peripheral nervous system were observed at mid-gestation stages. Strikingly, the altered phenotype at caudal levels included a posterior truncation of the tail, mildly affecting Cdx2 heterozygotes, but more severely affecting Cdx1/Cdr2 double heterozygotes and Cdx1 null/Cdx2 heterozygotes. Mutations in Cdx1 and Cdx2 therefore also interfere with axis elongation in a cooperative way. The function of Cdx genes in morphogenetic processes during gastrulation and tail bud extension, and their relationship with the Hox genes are discussed in the light of available data in Amphioxus, C. elegans, Drosophila and mice.

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Language(s): eng - English
 Dates: 2002-05
 Publication Status: Published in print
 Pages: -
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 Rev. Method: Peer
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Title: Development
Source Genre: Journal
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Pages: - Volume / Issue: 129 (9) Sequence Number: - Start / End Page: 2181 - 2193 Identifier: -