Murine Hox-1.7 homeo-box gene: cloning, chromosomal location, and expression.

Rubin, Michael R.; King, Walter E.; Toth, L E; Sawczuk, Ihor S.; Levine, Michael; D'Eustachio, P; Nguyen-Huu, M C

doi:10.1128/mcb.7.10.3836

Cited by 71 publications

(25 citation statements)

References 51 publications

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“…This generates several RNA variants which, if translated, encode a family of regulatory proteins. Together with the work reported for several other homeobox-containing genes, Drosophila Ubx (4,19,39,57) and bicoid (5), and guinea pig Hox-J .7 (43), it appears that the complexity of these loci extends to the production of multiple protein products, made possible by the alternative splicing of transcripts. We have also shown that the amounts of the individual Antp splicing variants relative to one another change over the course of development and differ between various larval tissues.…”

Section: Methodsmentioning

confidence: 99%

Alternative RNA splicing that is spatially regulated: generation of transcripts from the Antennapedia gene of Drosophila melanogaster with different protein-coding regions.

Stroeher¹,

Gaiser²,

Garber³

1988

Mol. Cell. Biol.

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We have shown previously that transcription of the Drosophila homeotic gene Antennapedia results in four major RNA species which differ in long 5'-and 3'-untranslated sequences. The protein-coding portion of these transcripts, however, is located in exons common to all. Using RNase protection assays and further cDNA clone isolation, we have now detected two alternative splicing events between exons of this region. These result in four RNA variations which, if translated, would encode a family of Antennapedia proteins. By analyzing transcripts from various developmental stages and isolated tissues, we show that alternative splicing is under strict temporal and spatial regulation. For example, while similar patterns of splicing were found for all wild-type thoracic imaginal disks examined, these differed distinctly from the patterns observed in neural tissues. Our results suggest that individual RNAs may be associated with different biological roles, and provide molecular evidence that the Antennapedia gene is involved in multiple functions.The Antennapedia (Antp) gene of Drosophila inelanogaster is a homeotic locus required for the proper development of thoracic segments. Mutants lacking this gene die as embryos, and cells of the thorax are transformed in an anterior direction (9,32,45,55). Antp also functions later in development in the imaginal disks (the presumptive adult tissues), promoting thoracic development while repressing the development of head structures (1,46,54). These roles are further exemplified by dominant mutations of this locus which cause abnormal activation of Antp expression in head imaginal disks. This ectopic transcription results in the transformation of head structures into thoracic tissues (12,22).Structurally, the Antp gene represents a complex transcriptional unit (22,27,48,53). It is composed of two functionally independent promoters, two polyadenylation sites, and eight exons spanning more than 100 kilobases (kb) of genomic DNA sequence (Fig. 1A). Four major classes of Antp transcripts are produced, two 5.0 and two 3.5 kb in size (Fig. 1B). These RNAs differ by extensive 5'-and 3'-untranslated sequences but share a common open reading frame (ORF) region involving exons 5 through 8.The localization of the Antp RNAs and proteins provides molecular evidence for its involvement in thoracic development. These products are found in a complex distribution pattern which undergoes dynamic changes as development proceeds. During early embryogenesis, both Antp RNAs and proteins are detected throughout the thoracic and abdominal regions, whereas by the end of this period and throughout the larval instar stages, these products are much more restricted to the thoracic segments (7,22,29,32,53,58). Within these domains of expression, Antp is active in both the ectoderm (epidermal and neural tissues) and the mesoderm. However, its products are usually detected in only a subset of the cells within a given region. (26,42). An example with consequences for Drosophila development is the finding that t...

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Section: Methodsmentioning

confidence: 99%

Alternative RNA splicing that is spatially regulated: generation of transcripts from the Antennapedia gene of Drosophila melanogaster with different protein-coding regions.

Stroeher¹,

Gaiser²,

Garber³

1988

Mol. Cell. Biol.

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“…The two major mouse homeo box clusters, Hox-1 and Hox-2, are located on chromosomes 6 and 11, respectively (Hart et al 1985;Bucfin et al 1986}. To date, the Hox-1 cluster has at least seven members Rubin et al 1987), and the Hox-2 cluster has five (Hart et al 1987); however, the size and organization of the clusters has not been completely established.…”

Section: }mentioning

confidence: 99%

Characterization of a murine homeo box gene, Hox-2.6, related to the Drosophila Deformed gene.

Graham¹,

Papalopulu²,

Lorimer³

et al. 1988

Genes Dev.

145

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The Hox-2 locus on chromosome 11 represents one of the major clusters of homeo-box-containing genes in the mouse. We have identified two new members (Hox-2.6 and Hox-2. 7), which form part of this cluster of seven linked genes, and it appears that the Hoxo2 locus is related by duplication and divergence to at least one other mouse homeo box cluster, Hox-1. The Hox-2.6 gene encodes a predicted protein of 250 amino acids, which displays extensive similarity in multiple regions to certain mouse, human, Xenopus, and zebra fish homeo domain proteins. The Drosophila Deformed (Dfd) gene also shares these same regions of similarity, and based on this sequence conservation, we suggest that Hox-2.6 forms part of a vertebrate 'Dfd-like' family. Hox-2.6 is expressed in fetal and adult tissues and is modulated during the differentiation of F9 teratocarcinoma stem cells.In situ hybridization analysis of mouse embryos shows that the Hox-2.6 is expressed in ectodermal derivatives:spinal cord, hindbrain, dorsal root ganglia, and the Xth cranial ganglia. In the central nervous system, expression is observed in the most posterior parts of the spinal cord, with the anterior limit residing in a region of the hindbrain and no expression in the mid-or forebrain. In mesodermal structures, Hox-2.6 is expressed in the kidney, the mesenchyme of the stomach and lung, and the longitudinal muscle layer of the gut. Expression has not been observed in derivatives of embryonic endoderm. The patterns of Hox-2.6 expression in both mesoderm and ectoderm are spatially restricted and may reflect a role for the gene in the response to or establishment of positional cues in the embryo.

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“…This stage of embryogenesis has been studied most extensively for homeo box gene expression, because in many cases it is the time when maximal transcript levels are seen by Northern or RNase protection analysis of total embryo RNA (Colberg-Poley et al 1985;Jackson et al 1985;Awgulewitsch et al 1986;Joyner and Martin 1987;Rubin et al 1987). By this time, all the major systems of the body have been established.…”

Section: Embryos About Two-thirds Through Gestation (125 Days Pc; Smentioning

confidence: 99%

“…It may be significant that close genetic linkage has been established between some mouse homeo box genes and known developmental mutations, e.g., between En-1 and Dominant hemimelia Joyner and Martin 1987); £22-2 and Hemimelic extra toes, Hammertoe, and reeler ; the Hox-1 cluster and Hypodactyly (Mock et al 1987;Rubin et al 1987); and the Hox-2 cluster and tail short (Munke et al 1986;Fienberg et al 1987). However, it should be stressed that allelism has not been demonstrated in any of these cases.…”

Section: Minal-j)mentioning

confidence: 99%