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F H Ruddle

Publications and source records attributed to F H Ruddle.

At least 37 records · Page 2Linked to original sources
PubMed1994

Chromosomal location and some structural features of human clathrin light-chain genes (CLTA and CLTB).

Two human clathrin light-chain genes have been defined. The gene (CLTA) encoding the LCa light chain maps to the long arm of chromosome 12 at 12q23-q24 and that encoding the LCb light chain (CLTB) maps to the long arm of chromosome 4 at 4q2-q3. Isolation and characterization of partial genomic clones encoding human LCa and LCb reveal the neuron-specific insertions of the LCa and LCb proteins to be encoded by discrete exons, thus proving that clathrin light chains undergo alternate mRNA splicing to generate tissue-specific protein isoforms. The insertion sequence of LCb is encoded by a single exon and that of LCa by two exons. The first of the two neuron-specific LCa exons is homologous to the corresponding LCb exon. An intronic sequence of the LCb gene with similarity to the second neuron-specific exon of the LCa gene has been identified.

Animals↗
PubMed1994

Mouse homeobox gene Dbx: sequence, gene structure and expression pattern during mid-gestation.

Homeobox genes regulate multiple aspects of mouse development including the axial patterning in the central nervous system. Some of the more divergent members of this gene family are expressed in the anterior region of the central nervous system where the Hox genes are not expressed. We previously reported the isolation of a mouse homeobox gene, Dbx, from the forebrain. Here we describe its genomic structure, complete cDNA sequence, characterization of the basal promoter and the expression pattern at different stages of the developing embryo. During early and mid-gestation, Dbx expression is restricted to the telencephalon, diencephalon, dorsal mesencephalon and spinal cord. At later gestational stages, Dbx expression continues in the dorsal mesencephalon and diencephalon, in which expression is more restricted than at the earlier stages. Dbx transcripts were also detected in the primitive cerebellum. At all stages, the Dbx expressing regions contain a high proportion of proliferating cells, suggesting a role for Dbx in patterning the central nervous system during embryogenesis.

Amino Acid Sequence↗
PubMed1994

Gene loss and gain in the evolution of the vertebrates.

Homeobox cluster genes (Hox genes) are highly conserved and can be usefully employed to study phyletic relationships and the process of evolution itself. A phylogenetic survey of Hox genes shows an increase in gene number in some more recently evolved forms, particularly in vertebrates. The gene increase has occurred through a two-step process involving first, gene expansion to form a cluster, and second, cluster duplication to form multiple clusters. We also describe data that suggests that non-Hox genes may be preferrentially associated with the Hox clusters and raise the possibility that this association may have an adaptive biological function. Hox gene loss may also play a role in evolution. Hox gene loss is well substantiated in the vertebrates, and we identify additional possible instances of gene loss in the echinoderms and urochordates based on PCR surveys. We point out the possible adaptive role of gene loss in evolution, and urge the extension of gene mapping studies to relevant species as a means of its substantiation.

Amino Acid Sequence↗
PubMed1993

Expansion of the Hox gene family and the evolution of chordates.

Homeobox genes encode DNA-binding transcription regulators that participate in the formation of embryonic pattern or contribute to cell-type specificity during metazoan development. Homeobox genes that regulate axial patterning and segmental identity (Hox/HOM genes) share a conserved clustered genomic organization. Mammals have four clusters that have likely arisen from the duplication of a single ancestral cluster. The number of Hox-type genes in other deuterostomes was estimated by using a polymerase chain reaction sampling method. Increased Hox gene complements are associated with the appearance of chordate and vertebrate characters. Our data suggest the presence of one Hox cluster in the acorn worm, a hemichordate; two Hox clusters in amphioxus, a cephalochordate; and three in the lamprey, a primitive vertebrate.

Animals↗
PubMed1993

A homeobox gene of the Antennapedia class is required for human adult erythropoiesis.

In this report we investigate the role of homeobox genes of the Antennapedia class in adult erythropoiesis, the process by which erythrocytes are formed in the bone marrow. We initially identified Hox genes expressed in mouse erythroleukemia cells by a PCR technique using degenerate primers capable of detecting most of the known genes in Hox clusters 1-4. Four different transcripts, Hox-3.3, -3.5, -3.6, and -4.3 were identified. An antisense oligonucleotide directed against HOX3C (human homologue of Hox-3.3) was used to study the effect of the colony formation by human erythroid progenitor cells. The oligonucleotide inhibited the formation of colony-forming unit erythroid-derived colonies but did not affect the size or degree of hemoglobinization. The more primitive erythroid burst-forming unit colonies or myeloid colonies were not affected. These results show that Hox-3.3 is involved in an early step in the proliferation of the erythroid colony-forming unit subset of progenitor cells.

Adult↗
PubMed1993

Physical linkage of the murine Hox-b cluster and nerve growth factor receptor on yeast artificial chromosomes.

Evidence derived from sequence comparisons and the genomic organization of the murine Antennapedia-class homeobox gene clusters suggest that they arose from a primordial cluster through a process of gene duplication and divergence followed by cluster duplication. A large chromosomal domain surrounding the ancestral homeobox cluster also appears to have been duplicated and has remained relatively stable since the divergence of humans and rodents. To test the extent of the duplicated chromosomal domain, we have initiated physical mapping studies of the regions surrounding the four murine homeobox clusters using pulsed-field gel electrophoresis and yeast artificial chromosome cloning. In this study, we present a long-range restriction map of mouse chromosome 11 spanning 1500 kb in the region surrounding the Hox-b cluster. We have determined that the gene for the nerve growth factor receptor is tightly linked to the Hox-b complex and is located within 50 kb of the Hox-b 1 gene at the 3' end of the cluster. Four yeast artificial chromosomes have been isolated and characterized by the polymerase chain reaction, long-range restriction mapping, and Southern blotting. Two clones of 150 and 300 kb contain the entire Hox-b cluster and the nerve growth factor receptor gene. A 440-kb clone contains the 3' end of the Hox-b cluster, the nerve growth factor receptor gene, and extends downstream. A 210-kb clone contains the 5' end of the Hox-b cluster and extends upstream. These clones confirm the pulsed-field restriction map of uncloned mouse DNA and represent a contig of approximately 600 kb of cloned material from mouse chromosomes 11.

Animals↗
PubMed1993

Early evolutionary origin of major homeodomain sequence classes.

We have analyzed the relationships of 337 homeodomain and related sequences using a distance matrix approach. Based on our results, homeodomain sequences can be classified into at least 30 distinguishable classes. Sequences belonging to the same class are highly similar to each other but there are no obvious close relationships between the separate classes. Since many of these classes each contain sequences from quite diverged organisms, we conclude that these separate classes of homeodomain sequences were established early during evolution.

Amino Acid Sequence↗
PubMed1993

Multiple Hox/HOM-class homeoboxes in Platyhelminthes.

The importance of the Hox/HOM class of homeobox genes in early anterior-posterior pattern formation and the conserved genomic organization of this gene family provides an interesting study in genome evolution. The Platyhelminthes (flatworms) are a basal metazoan group with a simple bilateral body plan. We used the polymerase chain reaction (PCR) to detect Hox/HOM-class homeobox genes from species representing two classes of flatworms. Seven planarian and five trematode Hox/HOM-class homeoboxes were found. The sequences of the genes are consistent with the presence of one Hox/HOM-type cluster in the flatworms. Further analysis of this putative cluster may be expected to provide outgroup information for studying the evolution of the Hox/HOM clusters in the higher metazoa.

Amino Acid Sequence↗
PubMed1993

Functional analysis of the mouse homeobox gene HoxB9 in Drosophila development.

Mammalian genomes contain clusters of homeobox genes (Hox-C, HOX-C) which are structurally similar to the homeotic genes of the Drosophila HOM complex. One method for assessing the functional similarity of particular Drosophila HOM and mammalian Hox genes is to test the ability of Hox genes to induce homeotic phenotypes when expressed in developing Drosophila. Here we describe such functional tests using mouse HoxB9 (formerly Hox-2.5), whose closest structural relative in Drosophila is Abdominal-B. When expressed from a heat shock promoter, HoxB9 induces transformations of head towards more posterior identities in Drosophila larvae and adults. These transformations share some similarities with the phenotypic effects produced by ectopically expressed Abdominal-B, but are also similar to the transformations induced by Antennapedia and mouse HoxB6 (Hox-2.2), suggesting that HoxB9 specifies a positional identity that is intermediate between Antennapedia and Abdominal-B.

Amino Acid Sequence↗
PubMed1993

Evolution of a regulatory gene family: HOM/HOX genes.

With the increasing accumulation of data on the presence of the HOM/HOX class of homeobox genes in the animal kingdom, and with new comparative analyses of these data, strong evolutionary conservation is apparent. It is clear that HOM/HOX genes and their roles in pattern formation were established early during the evolution of major phyla. The functional indications that this system is utilized in quite diverged organisms attest to the fundamental roles of homeobox genes in organismal development.

Animals↗
PubMed1992

Expression pattern of a murine homeobox gene, Dbx, displays extreme spatial restriction in embryonic forebrain and spinal cord.

Homeobox genes specify regional identity during development. A homeobox sequence that we have named Dbx was isolated from 13.5-day embryonic mouse telencephalon cDNA. The Dbx homeodomain shows highest sequence homology to Drosophila H2.0 and chicken CHox E. We report here the expression pattern of Dbx during mouse embryogenesis. In situ hybridization analyses indicate that Dbx is expressed exclusively within the embryonic central nervous system in a highly restricted manner. Dbx transcripts are detected within a region of the prospective cerebral cortex of the midgestation telencephalon. Dbx is also expressed in the diencephalon as well as in two thin continuous columns of neuroblasts within the hindbrain and spinal cord. This expression is limited to regions of active mitosis. Dbx may act to specify subsets of neuroblasts during the development of the central nervous system.

Amino Acid Sequence↗
PubMed1992

Genetic linkage analysis of the murine developmental mutant velvet coat (Ve) and the distal chromosome 15 developmental genes Hox-3.1, Rar-g, Wnt-1, and Krt-2.

We have identified restriction fragment length polymorphisms between Mus musculus and Mus spretus for the Chromosome 15 loci Hox-3, Wnt-1, Krt-2, Rar-g, and Ly-6. We followed the inheritance of these alleles in interspecific genetic test crosses between velvet coat (Ve) heterozygotes and M. spretus. The results suggest a gene order and recombination distances (in cM) of Ly-6-22-Wnt-1-2-Ve/Krt-2/Rar-g-3-Hox-3. No recombination was found between Ve, Krt-2, and Rar-g. The data also provide evidence for the hypothesis of a large-scale genomic duplication involving homologous gene pairs on mouse Chromosomes 15 and 11.

Animals↗
PubMed1992

Chromosome assignments of the human TNF p55 and p75 receptor genes.

At least two different receptor molecules have been described that are capable of binding tumor necrosis factor alpha, a cytokine that plays an important role in inflammation and antitumor activity. Comparative analyses at the nucleotide sequence level suggest that these receptors are members of a newly defined protein family that also includes human and rat nerve growth factor receptors. In this study, we determine the chromosome assignments of the human TNF alpha receptor genes, one of which may have evolved as part of a conserved Hox locus-containing chromosome segment.

Base Sequence↗
PubMed1992

Repression of the beta-amyloid gene in a Hox-3.1-producing cell line.

Mammalian homeobox genes are widely expressed in the developing central nervous system and are postulated to control developmental processes by regulating gene expression at the transcriptional level. In vitro studies have identified consensus DNA sequences that contain an ATTA core as sites for interaction with homeodomain proteins. Such elements have been found in the upstream regulatory region of the gene encoding beta-amyloid precursor protein, which is associated with the neurological disorder Alzheimer disease. As the beta-amyloid precursor protein gene is also expressed in the developing central nervous system and appears to play a role in cellular regulatory processes, we have examined the possibility that a homeobox gene product can regulate its transcription. We demonstrate by Northern blot analyses and transfection experiments that the expression of the beta-amyloid precursor protein gene is decreased in cultured cells expressing the mouse homeobox gene Hox-3.1.

Amyloid beta-Protein Precursor↗
PubMed1992

Genetic mapping of a new homeobox gene to mouse chromosome 7.

A newly identified homeobox gene designated Dbx has been mapped to mouse Chromosome (Chr) 7. This gene is expressed in a restricted manner in developing mouse brain and spinal cord and has amino acid sequence similarities with members of the homeobox gene family such as Drosophila H2.0 and mouse Hlx. Using a fragment of the Dbx cDNA as a probe, a PstI restriction fragment length polymorphism was used to determine genotypes of 144 progeny from an interspecific backcross. Segregation analysis revealed linkage of Dbx with six prepositioned reference loci on mouse Chr 7. No recombination was observed between Dbx and Odc-rs6, indicating that Dbx lies approximately 25 cM distal to the Chr 7 centromere in a region that has conserved linkage relationships with regions of human Chrs 11 and 19.

Animals↗