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PubMed1996

Mouse cathepsin K: cDNA cloning and predominant expression of the gene in osteoclasts, and in some hypertrophying chondrocytes during mouse development.

We have constructed cDNA clones covering the entire coding region of mouse, human and rabbit preprocathepsin K mRNA for studies on bone turnover. The clone pMCatK-1 for mouse cathepsin K shares 87% nucleotide homology with the corresponding human and rabbit sequences. Analysis of a panel of mouse tissues for tissue distribution of cathepsin K mRNA revealed the highest levels in musculoskeletal tissues: bone, cartilage and skeletal muscle. In situ hybridization of developing mouse embryos was performed to identify the cellular source of cathepsin K mRNA. The strongest mRNA signal was detected in osteoclasts of bone, identified in serial sections by positive TRAP staining. Cathepsin K mRNA was also observed in some hypertrophic chondrocytes of growth cartilages. Association of cathepsin K production with degradation of bone and cartilage matrix suggests that this enzyme and its mRNA levels could serve as markers for matrix degradation in diseases affecting these tissues.

Aging↗

PubMed1994

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31): alternatively spliced, functionally distinct isoforms expressed during mammalian cardiovascular development.

The establishment of the cardiovascular system represents an early, critical event essential for normal embryonic development. An important component of vascular ontogeny is the differentiation and development of the endothelial and endocardial cell populations. This involves, at least in part, the expression and function of specific cell surface receptors required to mediate cell-cell and cell-matrix adhesion. Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) may well serve such a function. It is a member of the immunoglobulin superfamily expressed by the entire vascular endothelium in the adult. It is capable of mediating adhesion by a heterophilic mechanism requiring glycosaminoglycans, as well as by a homophilic, glycosaminoglycan independent, mechanism. It has been shown to regulate the expression of other adhesion molecules on naive T cells. This report documents by RT-PCR and immunohistochemical analysis the expression of PECAM-1 during early post implantation mouse embryo development. PECAM-1 was expressed by early endothelial precursors first within the yolk sac and subsequently within the embryo itself. Interestingly, embryonic PECAM-1 was expressed as multiple isoforms in which one or more clusters of polypeptides were missing from the cytoplasmic domain. The sequence and location of the deleted polypeptides corresponded to exons found in the human PECAM-1 gene. The alternatively spliced isoforms were capable of mediating cell-cell adhesion when transfected into L-cells. The isoforms differed, however, in their sensitivity to a panel of anti-PECAM-1 monoclonal antibodies. These data suggest that changes in the cytoplasmic domain of PECAM-1 may affect its function during cardiovascular development, and are consistent with our earlier report that systematic truncation of the cytoplasmic domain of human PECAM-1 resulted in changes in its ligand specificity, divalent cation and glycosaminoglycan dependence, as well as its susceptibility to adhesion blocking monoclonal antibodies. This is the first report of naturally occurring alternatively spliced forms of PECAM-1 having possible functional implications.

Amino Acid Sequence↗

PubMed2002

Human endomucin: distribution pattern, expression on high endothelial venules, and decoration with the MECA-79 epitope.

Endomucin is a typical sialomucin that we recently identified on the surface of mouse endothelial cells and on putative hematopoetic clusters of the dorsal aorta in the embryo. We have generated a panel of monoclonal antibodies (mAbs) against the extracellular part of human endomucin and polyclonal antibodies against the cytoplasmic part. Using immunohistochemistry endomucin was specifically detected on endothelial cells of blood and lymphatic vessels of all analyzed human tissues. In addition, the polyclonal antibodies stained the epithelium of the epidermis as well as epithelial and myoepithelial cells of the eccrine and apocrine glands in the skin. This nonendothelial staining could only be seen with a subset of mAbs if the staining procedure was amplified. Although high endothelial venules (HEVs) were not significantly stained with mAbs against endomucin, the polyclonal antibodies clearly detected endomucin on HEVs in lymphatic organs of the mouse and human, suggesting HEV-specific glycosylation affecting recognition by the mAbs. Indeed, endomucin isolated from human and mouse lymphoid organs carried the MECA-79 epitope that defines a set of L-selectin ligands on HEVs called peripheral node addressins. We conclude that human and mouse endomucin are endothelial sialomucins with the potential to function as L-selectin ligands.

Amino Acid Sequence↗

PubMedDate not supplied

Growth suppression activity of the PTEN tumor suppressor gene in human endometrial cancer cells.

The AKT proteins are constitutively activated in several types of human cancers, which may play a role in carcinogenesis. In this study, we examined the activation of AKT in a panel of human endometrial cancer cell lines and tumor samples in this study. Two endometrial cancer cell lines, Ishikawa (ISK) and RL-95 and several tumor samples showed elevated levels of phosphorylated AKT PTEN, which is mutated in 45% of endometrial cancers, is a negative regulator of AKT. We examined the growth suppression activity of PTEN in ISK and KLE endometrial cancer cells. Expression of PTEN significantly suppressed the growth of both cell clines. In primary rat embryo fibroblasts, PTEN also inhibited malignant transformation mediated by ras and c-myc oncogenes. These two oncogenes are commonly mutated or amplified in endometrial cancer. These results suggest that PTEN may be a potent therapeutic agent for endometrial cancer.

Animals↗

PubMed1995

Neuroblast long-term cell cultures from human fetal olfactory epithelium respond to odors.

Primary cell cultures from human fetal olfactory neuroepithelium have been isolated, cloned, and propagated in continuous in vitro culture for approximately 1 year. The two clones we report here synthesize both neuronal proteins and olfactory-specific markers as well as the putative olfactory neurotransmitter, carnosine. In addition, patchclamp experiments reveal that these cells are electrically excitable. Following exposure to a panel of aromatic chemicals one of the cell cultures shows a specific increase in intracellular cAMP, indicating that some degree of functional maturity is expressed in vitro. The results suggest that these cells originate from the "stem cell" compartment that gives rise to mature olfactory receptor neurons. These long-term cell cultures represent models that will be useful in studying the mechanism(s) of olfaction and the regulation of olfactory neurogenesis and differentiation.

Abortion, Legal↗

PubMed2001

A prime-boost immunisation regimen using DNA followed by recombinant modified vaccinia virus Ankara induces strong cellular immune responses against the Plasmodium falciparum TRAP antigen in chimpanzees.

Two chimpanzees were vaccinated intramuscularly against malaria using plasmid DNA expressing the pre-erythrocytic antigens thrombospondin related adhesion protein (PfTRAP) and liver stage specific antigen-1 (PfLSA-1) of Plasmodium falciparum together with GM-CSF protein. A recombinant modified vaccinia virus Ankara (MVA) expressing PfTRAP was injected intramuscularly 6 weeks later to boost the immune response. This sequence of antigen delivery induced a specific and long-lasting T cell and antibody response to PfTRAP as detected by ELISPOT assay and ELISA. Antibody responses were detected after four DNA injections, and were boosted by injection of recombinant MVA expressing PfTRAP. Interferon-gamma secreting antigen-specific T cells were detected in both animals, but only after boosting with recombinant MVA. By screening a panel of PfTRAP-derived peptides, an epitope was identified that was recognized by cytotoxic T lymphocytes in one of the chimpanzees studied. T cells specific for this epitope were present in PBMCs and liver-infiltrating lymphocytes at a frequency of between 1 in 200 and 1 in 500. The high immunogenicity of this prime-boost regimen in chimpanzees supports further assessment of this delivery strategy for the induction of protection against P. falciparum malaria in humans.

Animals↗

PubMed2002

Hox gene expression in adult tissues with particular reference to the adrenal gland.

In comparison to the embryo, very little work has been carried out on the expression and role of Hox genes in the adult animal. An expression profile of all 39 vertebrate Hox genes on a select panel of adult human tissues reveals that in fact these genes are widely expressed throughout the adult human and a colinear pattern of expression is displayed similar to that of the developing embryo. Of particular interest is the abundance of Hox genes that are expressed within the adult adrenal gland. Adrenal cortical cells are continuously renewed to sustain production of zonal steroids. Cell proliferation occurs at the periphery of the cortex and cells are then displaced centripetally, phenotypically switching as they migrate through the gland before undergoing apoptosis at the zona reticularis/medullary boundary. It is still unclear which mechanisms cause the cells to differentiate as they cross the zonal boundaries and we hypothesise that Hox genes may be involved in the phenotypic switching of the adrenocortical cells. In situ hybridisation experiments were carried out on adult rat adrenal gland sections and Hox gene expression was localized within the zonal borders, coinciding with the localization of cells that undergo phenotypic differentiation, and thus supporting our hypothesis that Hox genes may be involved in the phenotypic switching of the adrenocortical cells. As in the developing embryo, the genes display colinear expression with the 3' Hox genes being expressed within the outer gland and the 5' genes within the inner zones.

Adrenal Glands↗

PubMed1990

Mouse Hox-3.4: homeobox sequence and embryonic expression patterns compared with other members of the Hox gene network.

A putative mouse homeobox gene (Hox-3.4) was previously identified 4kb downstream of the Hox-3.3 (Hox-6.1)* gene (Sharpe et al. 1988). We have now sequenced the Hox-3.4 homeobox region. The predicted amino acid sequence shows highest degree of homology in the mouse with Hox-1.3 and -2.1. This, together with similarities in the genomic organisation around these three genes, suggests that they are comembers of a subfamily, derived from a common ancestor. Hox-3.4 appears to be a homologue of the Xenopus Xlhbox5 and human cp11 genes (Fritz and De Robertis, 1988; Simeone et al. 1988). Using a panel of mouse-hamster somatic cell hybrids we have mapped the Hox-3.4 gene to chromosome 15. From the results of in situ hybridization experiments, we describe the distribution of Hox-3.4 transcripts within the 12 1/2 day mouse embryo, and we compare this with the distributions of transcripts shown by seven other members of the Hox gene network. We note three consistencies that underlie the patterns of expression shown by Hox-3.4. First, the anterior limits of Hox-3.4 transcripts in the embryo are related to the position of the Hox-3.4 gene within the Hox-3 locus. Second, the anterior limits of Hox-3.4 expression within the central nervous system are similar to those shown by subfamily homologues Hox-2.1 and Hox-1.3, although the tissue-specific patterns of expression for these three genes show many differences. Third, the patterns of Hox-3.4 expression within the spinal cord and the testis are very similar to those shown by a neighbouring Hox-3 gene (Hox-3.3), but they are quite different from those shown by Hox-1 genes (Hox-1.2, -1.3 and -1.4).

Amino Acid Sequence↗

PubMed1997

Immunohistochemical analysis of human embryos and fetuses: an insight into the mechanism of subversion of antigenic differentiation in neoplasia.

OBJECTIVES: Immunohistochemical identification of intermediate filaments and other cell identity markers is of immense value in diagnostic tumor pathology. However, the literature contains many examples of inappropriate expression of markers by various tumors or coexpression of two or more markers supposedly specific for different cell types. The present study investigated this subversion of antigen differentiation in tumors by using developing tissues as a model. MATERIALS AND METHODS: Twenty-five human embryos and fetuses of 4 to 24 weeks' gestation were studied. An indirect immunoperoxidase method was applied to formalin-fixed, paraffin-embedded sections using a panel of 13 commonly used cell identity markers including intermediate filaments. RESULTS: During early development, vimentin was found to be coexpressed with cytokeratin in surface ectoderm, developing notochord, renal tubule epithelium, and intestinal mucosa. It coexpressed with glial fibrillary acidic protein in developing neuroglial tissue, with S100 in cartilage, and with skeletal muscle markers in myotubules. Hence, vimentin represents immaturity of tissues and is coexpressed with specific cell markers to be eventually replaced by the latter. Transbarrier expression of cytokeratin in smooth muscle was also noted. CONCLUSION: The aberrant expression of antigens in neoplastic tissues, as reported in the literature, simulates the varying expression of antigens in immature tissues during development. Hence, it is proposed that the phenomenon of antigenic subversion in neoplasia is related to the process of maturation and differentiation.

Antibodies, Monoclonal↗

PubMed1995

Characterization of the complete genomic structure of the human WNT-5A gene, functional analysis of its promoter, chromosomal mapping, and expression in early human embryogenesis.

We report the complete genomic organization of the human WNT-5A gene, which encodes a cysteine-rich growth factor involved in cell-cell signaling during growth and differentiation. The gene comprises five exons with the terminal exon coding for a large 3'-untranslated region of approximately 6.5 kilobase pairs and utilizes multiple polyadenylation signals to generate at least four discrete transcripts. We discovered a new leader exon interrupted by a 411-base pair intron that was retained in our original cDNA cloning. The promoter region was located in a GpC-rich island and harbored numerous cis-acting elements including several GC boxes and Sp1, AP1, and AP2 binding motifs. It lacked TATA or CAAT boxes typical of housekeeping and growth factor genes. In support of this, primer extension revealed extension two transcription start sites. Transient cell transfection assays showed functional promoter activity for the 3.9-kilobase pair 5'-flanking region. Interestingly, internal and 5' deletions revealed tha the distal promoter was not required for full transcriptional activity and that the first 631 base pairs of WNT-5A harbored the strongest promoter activity. Using a panel of rodent-human hybrid DNAs carrying portions of chromosome 3p, we mapped the gene to 3p14.2-p21.1, between a constitutional and a familial renal cell carcinoma-associated translocation. In situ hybridization analyses of early human embryos at 28-42 days of gestation revealed that WNT-5A transcripts were not restricted to the developing brain and limbs but were also observed in the mesenchyme bordering the pharyngeal clefts and pouches and in the developing gonads and kidneys. The relatively high expression in the celomic epithelium and in the precursors of follicles and seminiferous tubules suggest a novel role for WNT-5A in germ-cell differentiation. This study provides the molecular basis for discerning the regulation of the WNT-5A gene and offers the opportunity to investigate genetic disorders linked to this important gene.

Animals↗

PubMed1984

Immunohistological characterization of lymphoid cell populations in the early human placental bed.

The distribution of leukocytes in first trimester human decidual tissue has been studied by using a panel of monoclonal antibodies in an indirect immunoperoxidase technique on acetone-fixed cryostat sections. The results indicate that bone marrow-derived cells are abundant in the placental bed and a proportion of these are HLA-DR positive. However, a major leukocyte population in the decidua of early pregnancy is of cells which carry the E-rosette receptor but which do not express peripheral pan-T cell antigens nor HLA-DR. The distribution of these cells suggests that they are endometrial granulocytes. A similar large number of cells express OKT 10, a marker of immature or activated cells. The presence of this unusual T lineage cell raises the possibility that a form of lymphocyte processing is occurring in the decidua in early pregnancy, perhaps in response to foetal antigens presented on trophoblast.

Antibodies, Monoclonal↗

PubMed2004

Spatio-temporal expression of the germ cell marker genes MATER, ZAR1, GDF9, BMP15,andVASA in adult bovine tissues, oocytes, and preimplantation embryos.

We have cloned the bovine homologue of Mater (maternal antigen that embryos require) cDNA, potentially the first germ cell-specific maternal-effect gene in this species. The 3297 base-pair longest open reading frame encodes a putative protein of 1098 amino acids with a domain organization similar to its human counterpart. By reverse transcription coupled to polymerase chain reaction, we have analyzed the spatiotemporal expression of MATER, along with other potential markers of germ cells or oocytes: ZAR1 (zygotic arrest 1), GDF9 (growth and differentiation factor 9), BMP15 (bone morphogenetic protein 15), and VASA. In agreement with a preferential oocyte origin, MATER, ZAR1, GDF9, and BMP15 transcripts were detected in the oocyte itself at a much higher level than in the gonads, while no significant expression was detected in our panel of somatic tissues (uterus, heart, spleen, intestine, liver, lung, mammary gland, muscle). In situ hybridization confirmed oocyte-restricted expression of MATER and ZAR1 within the ovary, as early as preantral follicle stages. VASA was highly represented in the testis and the ovary, and still present in the oocyte from antral follicles. Maternal MATER, ZAR1, GDF9, and BMP15 transcripts persisted during oocyte in vitro maturation and fertilization and in preimplantation embryo until the five- to eight-cell or morula stage, but transcription was not reactivated at the time of embryonic genome activation.

Animals↗

PubMed2002

The zebrafish mutant gene chardonnay (cdy) encodes divalent metal transporter 1 (DMT1).

Iron is an essential nutrient required for the function of all cells, most notably for the production of hemoglobin in red blood cells. Defects in the mechanisms of iron absorption, storage, or utilization can lead to disorders of iron-limited erythropoiesis or iron overload. In an effort to further understand these processes, we have used the zebrafish as a genetic system to study vertebrate iron metabolism. Here we characterized the phenotype of chardonnay (cdy), a zebrafish mutant with hypochromic, microcytic anemia, and positioned the mutant gene on linkage group 11. The cdy gene was isolated by a functional genomics approach in which we used a combination of expression studies, sequence analyses, and radiation hybrid panel mapping. We identified erythroid-specific genes using a whole embryo mRNA in situ hybridization screen and placed these genes on the zebrafish genomic map. One of these genes encoded the iron transporter divalent metal transporter 1 (DMT1) and colocalized with the cdy gene. We identified a nonsense mutation in the cdy allele and demonstrated that, whereas wild-type zebrafish DMT1 protein can transport iron, the truncated protein expressed in cdy mutants is not functional. Our studies further demonstrate the conservation of iron metabolism in vertebrates and suggest the existence of an alternative pathway of intestinal and red blood cell iron uptake.

Alleles↗

PubMed2005

Cloning and characterization of the mouse ortholog of mi-er1.

Mi-er1 is a fibroblast growth factor immediate-early gene whose expression is differentially regulated in breast tumours. MI-ER1 functions as a transcriptional repressor of a number of genes, including Sp1 target genes. The Xenopus and human orthologs have been described and here we report the characterization of the mouse gene and its products. Mouse mi-er1 is a single copy gene located on chromosome 4. It has the same intron-exon structure as the human gene with the exception of exon 3A, in which an upstream 3' splice acceptor is utilized. As described in humans, multiple transcripts are produced in the mouse, and we have isolated the mouse orthologs of the human N1-beta, N2-beta and N3-beta, all of, which differ in their N-terminal sequence. Furthermore, we have isolated a novel isoform, N4-beta, containing sequence from an additional exon located between exon 4 and exon 5 that produces an fourth alternate N-terminus. The human mi-er1 transcripts also include isoforms encoding two alternate C-termini, alpha and beta. Like Xenopus, only isoforms containing the beta C-terminus have been detected in the mouse. Expression analysis, using a panel of mouse tissues and embryos, revealed that the N1-beta and N3-beta are ubiquitously expressed while N4-beta is only expressed in testis. N2-beta is expressed in most tissues but was not detected in heart, brain, eye or skeletal muscle. Sequence comparison revealed 95% identity between mouse and human MI-ER1 isoforms and 72% identity between mouse and Xenopus. The most conserved region in the MI-ER1 protein is the SANT domain, which is identical in all three species. Further analysis of the SANT domain using sequences retrieved from the genome databases for rat, cow, chicken, zebrafish, trout and Xenopustropicalis revealed that this domain is highly conserved, with 88% identity among the 9 species. Moreover, an additional 10 residues C-terminal to the published end of this domain are 100% conserved, suggesting that in MI-ER1, the functional domain includes this extended sequence.

Amino Acid Sequence↗

PubMed1996

Primary structure, neural-specific expression, and chromosomal localization of Cux-2, a second murine homeobox gene related to Drosophila cut.

The cut locus of Drosophila encodes a diverged homeodomain-containing protein that is required for the development of external sensory (es) organs and other tissues. A homologous gene (Cux-1) that encodes a transcriptional repressor has been identified in the mouse and other mammals. We have identified a second murine homeobox-containing gene (designated Cux-2) that is structurally related to Drosophila cut. The murine Cux-2 homeobox was similar to Drosophila cut and encoded a homeodomain that contained a characteristic histidine residue at position 50. The predicted Cux-2 protein contained 1426 amino acids and included three internal 60-amino acid repeats (Cut repeats) that were previously found in Drosophila Cut and murine Cux-1. Unlike Cux-1, expression of Cux-2 was restricted to neural tissue. In the adult brain, Cux-2 was prominently expressed in neurons in the thalamus and limbic system. In embryos, Cux-2 was expressed in the developing central and peripheral nervous systems, including the telencephalon and peripheral ganglia of the trigeminal and glossopharyngeal nerves. A glutathione S-transferase fusion protein containing the carboxyl-terminal Cut repeat and homeodomain of Cux-2 exhibited sequence-specific binding to oligonucleotides derived from the promoter of the Ncam gene. Using an interspecific backcross panel, Cux-1 and Cux-2 were mapped to distinct loci that were genetically linked on distal chromosome 5. These results demonstrate that a family of homeobox genes related to Drosophila cut is located on chromosome 5 in the mouse. Cux-2 is expressed exclusively in the central and peripheral nervous systems, and the Cux-2 gene product binds to DNA in a sequence-specific manner. Cux-2 may encode a transcription factor that is involved in neural specification in mammals.

Amino Acid Sequence↗

PubMed1994

Further characterization of endometrial integrins during the menstrual cycle and in pregnancy.

OBJECTIVE: To profile the changes in integrin expression in cycling and pregnant endometrium. DESIGN: Immunohistochemistry was performed on endometrium from proliferative, early, and midsecretory phase and early pregnancy using a blinded panel of monoclonal antibodies directed against integrins. Closer examination of the cycle-dependent integrins was performed in 112 patients throughout the cycle and from the first trimester of pregnancy. SETTING: An academic teaching hospital. PATIENTS: Ovulatory women or women undergoing pregnancy termination. MAIN OUTCOME MEASURE: Staining intensity of each antibody in epithelial or stromal cells. RESULTS: Certain integrins were present constitutively throughout the menstrual cycle whereas others were expressed only during the luteal phase. Four integrins increased in the decidua of pregnancy. The timing of expression of the two cycle-dependent integrins (alpha 4 beta 1 and alpha v beta 3) framed the putative window of implantation and suggests a role in establishment of uterine receptivity. CONCLUSIONS: Our findings confirm the patterns of endometrial integrins and suggest important roles for integrins in the process of implantation and decidualization.

Antibodies, Monoclonal↗

PubMed2005

An interstitial deletion-insertion involving chromosomes 2p25.3 and Xq27.1, near SOX3, causes X-linked recessive hypoparathyroidism.

X-linked recessive hypoparathyroidism, due to parathyroid agenesis, has been mapped to a 906-kb region on Xq27 that contains 3 genes (ATP11C, U7snRNA, and SOX3), and analyses have not revealed mutations. We therefore characterized this region by combined analysis of single nucleotide polymorphisms and sequence-tagged sites. This identified a 23- to 25-kb deletion, which did not contain genes. However, DNA fiber-FISH and pulsed-field gel electrophoresis revealed an approximately 340-kb insertion that replaced the deleted fragment. Use of flow-sorted X chromosome-specific libraries and DNA sequence analyses revealed that the telomeric and centromeric breakpoints on X were, respectively, approximately 67 kb downstream of SOX3 and within a repetitive sequence. Use of a monochromosomal somatic cell hybrid panel and metaphase-FISH mapping demonstrated that the insertion originated from 2p25 and contained a segment of the SNTG2 gene that lacked an open reading frame. However, the deletion-insertion [del(X)(q27.1) inv ins (X;2)(q27.1;p25.3)], which represents a novel abnormality causing hypoparathyroidism, could result in a position effect on SOX3 expression. Indeed, SOX3 expression was demonstrated, by in situ hybridization, in the developing parathyroid tissue of mouse embryos between 10.5 and 15.5 days post coitum. Thus, our results indicate a likely new role for SOX3 in the embryonic development of the parathyroid glands.

Animals↗

PubMed2002

Inhibition of myogenin expression by activated Raf is not responsible for the block to avian myogenesis.

Activated Raf is a potent inhibitor of skeletal muscle gene transcription and myocyte formation through stimulation of downstream MAPK. However, the molecular targets of elevated MAPK with regard to myogenic repression remain elusive. We examined the effects of activated Raf on myogenin gene expression in avian myoblasts. Overexpression of activated Raf in embryonic chick myoblasts prevented myogenin gene transcription and myocyte differentiation. Treatment with PD98059, an inhibitor of MAPK kinase (MEK), restored myogenin expression but did not reinstate the myogenic program. Using a panel of myogenin promoter deletion mutants, we were unable to identify a region within the proximal 829-bp promoter that confers responsiveness to MEK. Interestingly, our experiments identified MEF2A as a target of Raf-mediated inhibition in mouse myoblasts but not in avian myogenic cells. Embryonic myoblasts overexpressing activated Raf were unable to drive transcription from a minimal myogenin promoter reporter, containing a single E-box and MEF2 site, to levels comparable with controls. Unlike mouse myoblasts, forced expression of MEF2A did not synergistically enhance transcription from the myogenin promoter in chick myoblasts, indicating that additional molecular determinants of the block to myogenesis exist. Results of these experiments further exemplify specie differences in the mode of Raf-mediated inhibition of muscle differentiation.

Animals↗