Pattern of transcription of the homeo gene Hox-3.1 in the mouse embryo.

Mouellic, H. Le; Condamine, Hubert; Brûlet, Philippe

doi:10.1101/gad.2.1.125

Cited by 68 publications

(40 citation statements)

References 42 publications

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“…Hoxc8 expression delay and thoracic anteriorization Our whole-mount in situ data of Hoxc8 transcripts in wild-type mouse embryos at different developmental stages confirm previously reported studies (Gaunt, 1988;Le Mouellic et al, 1988). Transcription initiates at the allantois at early 8 dpc and then the expression domain gradually moves anteriorly to all the tissues from 8 dpc to 9.5 dpc.…”

Section: Discussionsupporting

confidence: 78%

Enhancer timing of Hox gene expression: deletion of the endogenousHoxc8early enhancer

Juan

Ruddle

2003

Development

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The proper expression of Hox genes is necessary for the accurate patterning of the body plan. The elucidation of the developmental genetic basis of transcriptional regulation of Hox genes by the study of their cis-regulatory elements provides crucial information regarding the establishment of axial specification. In this report, we investigate the role of the early enhancer(EE) of the murine Hoxc8 gene to better understand its role in pattern formation. Previous reports show that knockouts of the endogenous Hoxc8 coding region result in a combination of neural, behavioral and skeletal phenotypes. In this report, we limit ourselves to a consideration of the skeletal abnormalities. Early reports from our laboratory based on exogenous transgenic reporter constructs implicate a 200 bp non-coding element 3 kb upstream of the Hoxc8 promoter as a crucial enhancer that regulates the transcription of Hoxc8. In the present work, we have deleted this regulatory region from the endogenous genome using embryonic stem cell technology. Our results show that the deletion of the EE results in a significant delay in the temporal expression of Hoxc8. We also show that the deletion of the EE does not eliminate the expression of the Hoxc8 protein, but delays the attainment of control levels of expression and anterior and posterior boundaries of expression on the AP axis. The temporal delay in Hoxc8 expression is sufficient to produce phenocopies of many of the axial skeletal defects associated with the complete absence of Hoxc8 gene product as previously reported for the Hoxc8-null mutation. Our results are consistent with emerging evidence that the precise temporal expression of Hox genes is crucial for the establishment of regional identities. The fact that the EE deletion does not eliminate Hoxc8expression indicates the existence of a Hoxc8 transcriptional regulatory apparatus independent to some degree of the Hoxc8 EE. In a comparison of our results with those reported previously by others investigating temporal control of Hox gene expression, we have discovered a structural similarity between the Hoxc8 EE reported here and a transcriptional control element located in the Hoxd11 region. We speculate that a distributed system of expression timing control may exist that is similar the one we propose for Hoxc8. Last, our data is consistent with the position that disparate regulatory pathways are responsible for the expression of Hoxc8 in the organogenesis of somites, neural tube and limb bud.

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Section: Discussionsupporting

confidence: 78%

Enhancer timing of Hox gene expression: deletion of the endogenousHoxc8early enhancer

Juan

Ruddle

2003

Development

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“…Consistent with the hypothesis that murine 3Present address: INSERM U. 257, Institut Jacques-Monod, Universit~ Paris VII, 75005 Paris, France homeo-box-containing (Hox) genes may regulate aspects of embryogenesis, the expression of Hox genes is restricted temporally and spatially during embryogenesis (Awgulewitsch et al 1986;Gaunt et al 1986;Dony and Gruss 1987;Gaunt 1987;Toth et al 1987;Utset et al 1987;Breier et al 1988;Featherstone et al 1988;Holland and Hogan 1988;Le Mouellic et al 1988;Sharpe et al 1988; for review, see Dressler and Gruss 1988). The regulatory potential of the homeo box genes is further substantiated by their ability to bind DNA (Desplan et al 1985;Fainsod et al 1986;Hoey and Levine 1988) and their nuclear localization (Odenwald et al 1987;Schulze et al 1987).…”

mentioning

confidence: 70%

A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine.

Duprey¹,

Chowdhury²,

Dressler³

et al. 1988

Genes & Development

196

112

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“…6 transcripts extend in both neurectoderm and mesoderm clearly more anteriorly than those of both Hox-1.4 and Hox-1.5, the genes located just upstream of Hox-] . 6 on the HOX-1 complex (Baron et al, 1987; Fainsod et al, 1987; Holland and Hogan, 1988b (LeMouellic et al, 1988). By days 10-11, Hox-1.6 transcripts are below our level of detection though other homeogenes are usually expressed at high levels Holland and Hogan, 1988a).…”

Section: Discussionmentioning

confidence: 99%

The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes.

1989

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This paper reports the cloning of the fourth major murine homeogene complex, HOX-5. The partial characterization of this gene cluster revealed the presence of two novel genes (Hox-5.2, 3) located at the 5' extremity of this complex. In situ hybridization experiments showed that these two genes are transcribed in very posterior domains during embryonic and foetal development. We also show that Hox-1.6, the gene located at the 3' most position in the HOX-1 complex, has a very anterior expression boundary during early development. These results clearly support the recently proposed hypothesis that the expression of murine Antp-like homeoboxcontaining genes along the antero-posterior developing body axis follows a positional hierarchy which reflects their respective physical positions within the HOX clusters, similar to that which is found for the Drosophila homeotic genes. Such a structural and functional organization is likely conserved in most vertebrates. Moreover, on the basis of sequence comparisons, we propose that the ordering of homeobox-containing genes within clusters has been conserved between Drosophila and the house mouse. Thus, very different body plans might be achieved, both in insects and vertebrates, by evolutionarily conserved gene networks possibly displaying similar regulatory interactions.

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Pattern of transcription of the homeo gene Hox-3.1 in the mouse embryo.

Cited by 68 publications

References 42 publications

Enhancer timing of Hox gene expression: deletion of the endogenousHoxc8early enhancer

Enhancer timing of Hox gene expression: deletion of the endogenousHoxc8early enhancer

A mouse gene homologous to the Drosophila gene caudal is expressed in epithelial cells from the embryonic intestine.

The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes.

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