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The role of maternal mitochondria during oogenesis, fertilization and embryogenesis.

This review examines the place of mitochondria in the life cycle through oogenesis, ovulation and early embryogenesis. Mitochondria are semi-autonomous organelles responsible for the bulk of oxidative energy production in the body. They play central roles in ageing, in apoptosis and in many non-Mendelian-inherited bioenergetic and neurological diseases. Originating as free alpha-proteobacteria that entered into a symbiotic relationship with the ancestral eukaryotic organisms, they now have a highly restricted genome of ~16 kb, encoding for 37 genes of the oxidative phosphorylation pathway. Mitochondria are inherited through the mother and special mechanisms have evolved to eliminate the contribution of the spermatozoon in early embryonic development. Most mitochondrial genes have become translocated to the nucleus, and nuclear and mitochondrial genes have co-evolved. This, coupled with a high mutation rate in the remaining mitochondrial DNA, has resulted in a high degree of concordance between them. Disharmony between nuclear and mitochondrial genes is thus likely to complicate cloning technology and the experimental reconstruction of chimeric embryos by cytoplasmic or nuclear transfer.

Animals↗

Spatial and temporal expression patterns of selenoprotein genes during embryogenesis in zebrafish.

Selenium is important for embryogenesis in vertebrates but little is known about the expression patterns and biological functions of most selenoprotein genes. Taking advantage of the zebrafish model, systematic analysis of selenoprotein gene expression was performed by in situ hybridization on whole-mount embryos at different developmental stages. Twenty-one selenoprotein mRNAs were analyzed and all of them exhibited expression patterns restricted to specific tissues. Moreover, we demonstrated that highly similar selenoprotein paralogs were expressed within distinct territories. Therefore, tissue- and development-specific expression patterns provided new information for selenoproteins of unknown function.

Animals↗

The T-box gene Tbx10 exhibits a uniquely restricted expression pattern during mouse embryogenesis.

The human TBX10 gene was previously identified from a genomic DNA sequence containing a partial open reading frame and was mapped to Chromosome 11q13, a chromosomal region associated with multiple inherited developmental disorders. Since mutations in several T-box family genes have been found to underlie distinct inherited developmental disorders, it has been speculated that TBX10 may be a candidate for one of the disease loci at Chromosome 11q13. To investigate the role of TBX10 in development and pathogenesis, we have isolated a full-length human TBX10 cDNA and cloned the mouse ortholog, Tbx10. Sequence analysis of cDNA clones and reverse transcription-polymerase chain reaction products revealed that the previously predicted TBX10 open reading frame (GenBank accession number AH006177) was incorrect. We have characterized the developmental expression patterns of Tbx10 during mouse embryogenesis by using in situ hybridization analyses. Our results show that Tbx10 mRNA expression is highly restricted and exhibits a unique spatio-temporal pattern during hindbrain development. These data will facilitate investigation of the role of TBX10 in development and disease.

Amino Acid Sequence↗

Lethality in PARP-1/Ku80 double mutant mice reveals physiological synergy during early embryogenesis.

Ku is an abundant heterodimeric nuclear protein, consisting of 70- and 86-kDa tightly associated subunits that comprise the DNA binding component of DNA-dependent protein kinase. Poly(ADP-ribose) polymerase-1 (PARP-1) is a 113-kDa protein that catalyzes the synthesis of poly(ADP-ribose) on target proteins. Both Ku and PARP-1 recognize and bind to DNA ends. Ku functions in the non-homologous end joining (NHEJ) repair pathway whereas PARP-1 functions in the single strand break repair and base excision repair (BER) pathways. Recent studies have revealed that PARP-1 and Ku80 interact in vitro. To determine whether the association of PARP-1 and Ku80 has any physiological significance or synergistic function in vivo, mice lacking both PARP-1 and Ku80 were generated. The resulting offspring died during embryonic development displaying abnormalities around the gastrulation stage. In addition, PARP-1-/-/Ku80-/- cultured blastocysts had an increased level of apoptosis. These data suggest that the functions of both Ku80 and PARP-1 are essential for normal embryogenesis and that a loss of genomic integrity leading to cell death through apoptosis is likely the cause of the embryonic lethality observed in these mice.

Animals↗

Further evidence that sperm nuclear proteins are necessary for embryogenesis.

We have recently presented evidence that the structural integrity of the mouse sperm nuclear matrix may be necessary for the proper unpackaging of sperm DNA for participation in embryogenesis. It is likely that the sperm nuclear matrix contributes to the organisation of the sperm DNA and its disturbance can seriously damage the paternal genome or its expression. In this work, we confirm our previous data and further suggest that even very subtle changes in the sperm nuclear structure may have a significant impact on embryo development. As reported previously, dithiothreitol (DTT) in the presence of an ionic detergent, ATAB, destabilized the nuclear matrix as measured by the halo assay, and oocytes injected with these nuclei failed to develop. We also discovered that omitting the protease inhibitor PMSF from the buffers used to extract spermatozoa prevented sperm injected into oocytes from participating in development. The organization of DNA into loop domains by the nuclear matrix in these nuclei appeared normal, as measured by the halo assay. Oocytes injected with sperm nuclei that had been washed with ATAB in the presence of phenylmethylsulphonyl fluoride (PMSF) but in the absence of DTT resulted in live births. Neither DTT treatment nor the absence of PMSF would be expected to disrupt the integrity of the paternal DNA. The data therefore suggest that even very subtle alterations in the structural proteins of the nucleus are enough to deprive sperm DNA of the ability to contribute to embryonic development.

Animals↗

The role of structural integrity of the fertilising spermatozoon in early human embryogenesis.

While the fertilising spermatozoon supplies the active centre directing the human zygote's first mitotic division, the relative contributions of the sperm head and tail (as well as the importance of the sperm's general structural integrity) to subsequent developmental processes remain incompletely studied. The sperm nucleus contains paternal chromatin necessary for restoration of a diploid genome, but the functional role of the sperm tail (either attached or dissected) in early human embryonic growth is not known. In this investigation using oocytes donated by in vitro fertilisation patients, human oocytes were injected with isolated sperm heads (n = 73), isolated sperm flagella (n = 11) or both (dissected sperm heads + free sperm tails, n = 26). The formation of bipronucleate zygotes was recorded for each method. Among oocytes surviving injection with isolated sperm heads, 44 of 66 (67%) formed two pronuclei. Of oocytes receiving only sperm tails, 2 of 11 (18%) displayed two pronuclei, but a single polar body was evident in both cases. When dissected spermatozoa parts (head + tail) were jointly injected, 12 of 26 (46%) developed two pronuclei. From embryos resulting from each of these three fertilisation regimes, blastomere biopsies were obtained and subjected to multiprobe fluorescent in situ hybridisation (FISH) analysis to detect mosaicism or aneuploidy arising from these experimental treatments. Only embryos with growth sufficient to permit sampling of at least two blastomeres were evaluated, and FISH analysis was successful in 25 of 29 (86%) embryos tested. Of 12 embryos derived from injection of an isolated sperm head, only one was normal diploid; the remaining 11 were mosaic. Both embryos resulting from injection of an unattached sperm tail were mosaic. Of 11 embryos generated from oocyte injection with sperm head + tail segments, 10 (91%) were mosaic and only one was normal diploid. Results from this study show that injection of isolated sperm segments can permit oocyte activation and bipronuclear formation. However, a high rate of mosaicism in human embryos originating from disrupted sperm or sperm components suggests that more than a 'sum of parts' is needed for later development. The structural integrity of the intact fertilising spermatozoon appears to contribute to normal human early embryogenesis.

Blastomeres↗

Translational control in early sea urchin embryogenesis: initiation factor eIF4F stimulates protein synthesis in lysates from unfertilized eggs of Strongylocentrotus purpuratus.

We have used cell-free translation systems from unfertilized eggs and embryos of the sea urchin Strongylocentrotus purpuratus to analyze the mechanisms limiting protein synthesis in early embryogenesis. Unfertilized egg lysates supplemented with nuclease-treated reticulocyte lysate were stimulated 2-4-fold in incorporation of radioactive amino acid into protein. Thirty-minute zygote lysates supplemented in this way were not stimulated. These results suggested that a component limiting translation in the unfertilized egg lysate was provided by the nuclease-treated lysate and that this component was no longer limiting protein synthesis following fertilization. In view of these results, partially fractionated lysates and individual purified translational components from mammalian cells were tested for stimulation of the unfertilized egg lysate. A 1000000g supernatant devoid of ribosomal subunits also stimulated the unfertilized egg lysate. Thus, the stimulation was not due to the addition of active ribosomal subunits but to soluble elements in the reticulocyte lysate. Of the soluble components tested, only the cap-binding protein complex eIF4F caused a dramatic stimulation of the unfertilized egg lysate (2-3.5-fold). The 30-min zygote lysate was not stimulated by eIF4F or by any of the other components tested, supporting the hypothesis that a block in the translational machinery is removed at fertilization. A rabbit reticulocyte shift assay was used to analyze whether mRNA is limiting in early development. When unfertilized egg lysate was added to the shift assay, there was no shift in radioactivity from 43S to 80S complexes, indicating the unfertilized egg mRNA is not available for translation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biliverdin during Xenopus laevis oogenesis and early embryogenesis.

Biliverdin is required for Xenopus laevis embryo dorsal axis formation. When the tetrapyrrole is inactivated by phototransforming it with ultraviolet light prior to the first division, the embryo fails to synthesize dorsal mRNAs, such as goosecoid or chordin, yet forms increased amounts of ventral transcripts, such as Vent 1, and, consequently, develops ventralized morphology. Here we describe the metabolism of biliverdin during oogenesis and early embryogenesis. Estrogen induces frog hepatocytes to synthesize biliverdin and vitelogenin. The two molecules form a complex that is secreted into and transported in the plasma to be taken up by the oocyte as it matures through its six stages of oogenesis. In the oocyte, the biliverdin-vitellogenin complex is processed and stored in the yolk platelets. In these organelles, biliverdin is associated entirely with the lipovitellin domain of the processed vitellogenin. Once the egg is fertilized, its biliverdin content decreases over a 5-6 h period to participate in the chemical machinery required for dorsal axis formation. This participation must be initiated during the period encompassing the first embryonic mitosis. The results describe the pathway that generates, transports, and stores biliverdin as part of oogenesis, define the time course for its utilization after fertilization, and link biliverdin to the metabolism of the phosphoglycolipometalloprotein, vitellogenin.

Animals↗

A role for SSeCKS, a major protein kinase C substrate with tumour suppressor activity, in cytoskeletal architecture, formation of migratory processes, and cell migration during embryogenesis.

SSeCKS is a major protein kinase C substrate which has tumour suppressor activity in models of src- and ras-induced oncogenic transformation. The mitogenic regulatory activity of SSeCKS is likely manifested by its ability to bind key signalling proteins such as protein kinases C and A and calmodulin, and to control actin-based cytoskeletal architecture. Rat SSeCKS shares extensive homology with human Gravin, an autoantigen in myasthenia gravis that encodes kinase scaffolding functions and whose expression pattern in fibroblasts and nerves suggests a role in cell motility. Here, we analyse the expression of SSeCKS and Gravin in rodent and human fibroblast and epithelial cell lines using antibodies specific or crossreactive for SSeCKS or Gravin. SSeCKS expression was then analysed in developing mouse embryos and in adult tissues. In the foetal mouse, early SSeCKS protein expression (E10-11) is focused in the loose mesenchyme, luminal surface of the neural tube, notochord, early heart and pericardium, urogenital ridge, and dorsal and ventral sections of limb buds. In later stages (E12-14), SSeCKS is widely expressed in mesenchymal cells but is absent in the spinal ganglia. By E15, SSeCKS expression is ubiquitous, although the staining pattern varies from being striated within smooth muscle sarcomeres to filamentous in mesenchymal and select epithelial cells. In the adult mouse, SSeCKS staining is relatively ubiquitous, with highest expression in the gonads, smooth and cardiac muscle, lung, brain and heart. High expression is also detected in fibroblasts and nerve fibres as well as in more specialized cells such as glomerular mesangial cells and testicular Sertoli cells. SSeCKS expression in the rat testes correlates with the induction of puberty, and in mature mouse spermatozoa, SSeCKS is found in peripheral acrosome membranes and in a helix-like winding pattern within the midsection. Periodic enrichments of SSeCKS are found in sperm midsections and in developing axons, suggesting a role in architectural infrastructure. As with Gravin, high SSeCKS expression is absent in most epithelial cells; however, in contrast to Gravin, SSeCKS is expressed in Purkinje cells, cardiac muscle, macrophages and hepatic stellate cells, indicating overlapping yet distinct patterns of tissue expression in the SSeCKS/Gravin family. The data suggest roles for SSeCKS in the control of cytoskeletal and tissue architecture, formation of migratory processes and cell migration during embryogenesis.

A Kinase Anchor Proteins↗

Characterization of Phaseolus vulgaris cDNA clones responsive to water deficit: identification of a novel late embryogenesis abundant-like protein.

Six cDNA clones from Phaseolus vulgaris, whose expression is induced by water deficit and ABA treatment (rsP cDNAs) were identified and characterized. The sequence analyses of the isolated clones suggest that they encode two types of late-embryogenesis abundant (LEA) proteins, a class-1 cytoplasmic low-molecular-weight heat shock protein (lmw-HSP), a lipid transfer protein (LTP), and two different proline-rich proteins (PRP). One of the putative LEA proteins identified corresponds to a novel 9.3 kDa LEA-like protein. During the plant response to a mild water deficit (psi w = -0.35 MPa) all genes identified present a maximal expression at around 16 or 24 h of treatment, followed by a decline in expression levels. Rehydration experiments revealed that those genes encoding PRPs and LTP transiently re-induce or maintain their expression when water is added to the soil after a dehydration period. This is not the case for the lea genes whose transcripts rapidly decrease, reaching basal levels a few hours after rehydration (4 h). Under water deficit and ABA treatments, the highest levels of expression for most of the genes occur in the root, excluding the ltp gene whose maximum expression levels are found in the aerial regions of the plant. This indicates that for these genes, both water deficit and ABA-dependent expression are under organ-specific control. The data presented here support the importance of these proteins during the plant response to water deficit.

Abscisic Acid↗

Expression and cellular localization of Atrab28 during arabidopsis embryogenesis.

The maize abscisic acid (ABA)-responsive gene rab28 has been shown to be ABA-inducible in embryos and vegetative tissues, expression being mostly restricted to vascular elements during late embryogenesis. In the course of an expressed sequence tags (ESTs) programme, we have isolated an Arabidopsis thaliana gene, Atrab28, encoding the orthologue of maize rab28. The Atrab28 cDNA is 1090 bp long, including a poly(A)+ stretch, and encodes a polypeptide of 262 amino acids. Atrab28 antibody against the recombinant protein recognizes a polipeptide of about 30 kDa and pI 6, in close agreement with the predicted molecular mass and pI. As for maize rab28, expression studies with Atrab28 revealed high specificity for embryo tissues, transcription being stimulated by the transcriptional activator abi3. In contrast, Atrab28 was not induced in vegetative tissues by ABA, osmotic stress or dehydration. The expression of Atrab28 mRNA and the accumulation of Atrab28 protein was largely restricted to provascular tissues of mature embryos and in the seed coat outer tegument and embryo and silique epidermis, as revealed by in situ hybridization and immunocytochemistry with anti-Atrab28 antibodies.

Abscisic Acid↗

Partial characterization of genes whose transcripts accumulate preferentially in cell clusters at the earliest stage of carrot somatic embryogenesis.

We attempted to identify genes that are preferentially expressed immediately after somatic cells divide to form cell clusters at the earliest stage of carrot somatic embryogenesis when they are not or barely expressed in non-embryogenic suspension-cultured cells in the presence of 2,4-D. Using the differential display technique, we isolated three cDNA clones, designated No. 43, No. 87 and No. 93. The No. 43 transcript was preferentially expressed in the earliest cell clusters, its level decreased drastically at the globular and heart-shaped and torpedo-shaped stages, and it was not detected in non-embryogenic suspension-cultured cells. No. 43 cDNA encoded a protein with homology to thaumatin-like proteins and the deduced positions of seven cysteine residues in the 63 amino acid sequence from the carboxyl terminus were identical to those in thaumatin-like proteins. The full-length nucleotide sequence of No. 93 cDNA was determined and its product was about 80% homologous to precursor of the 14 kDa proline-rich DC 2.15 protein of carrot at the amino acid level. However, the deduced amino acid sequence lacked the characteristic core of repeating Pro-X motifs found in DC 2.15. The No. 93 transcript accumulated preferentially in the earliest cell clusters but it was also detected at a low level in non-embryogenic suspension-cultured cells, unlike DC 2.15 transcripts that begin to accumulate in heart-shaped embryos before their level falls in torpedo-shaped embryos. No. 87 transcripts were expressed preferentially in the earliest cell clusters that has been incubated with 2,4-D but were also detected at a low level in suspension-cultured cells subcultured in the continued presence of 2,4-D. The No. 87 cDNA exhibited no significant homology to any sequences in databases.

2,4-Dichlorophenoxyacetic Acid↗

Ontogenesis of the snail, Helix aspersa: embryogenesis timetable and ontogenesis of GABA-like immunoreactive neurons in the central nervous system.

Late stages of embryogenesis in the terrestrial snail Helix aspersa L. were studied and a developmental timetable was produced. The distribution of gamma-aminobutyric acid-like immunoreactive (GABA-ir) elements in the CNS of the snail was studied from embryos to adulthood in wholemounts. In adults, approximately 226 GABA-ir neurons were located in the buccal, cerebral and pedal ganglia. The population of GABA-ir cells included four pairs of buccal neurons, three neuronal clusters in the pedal ganglia, two clusters and six single neurons in the cerebral ganglia. GABA-ir fibers were observed in all ganglia and in some nerves. The first detected pair of GABA-ir cells in the embryos appeared in the buccal ganglia at about 63-64% of embryonic development. Five pairs of GABA-ir cell bodies were observed in the cerebral ganglia at about 64-65% of development. During the following 30% of development three more pairs of GABA-ir neurons were detected in the buccal ganglia and over fifteen cells were detected in each cerebral ganglion. At the stage of 70% of development, the first pair of GABA-ir neurons was found in the pedal ganglia. In the suboesophageal ganglion complex, GABA-ir fibers were first detected at about 90% of embryonic development. In the posthatching period, the quantity of GABA-ir neurons reached the adult status in four days in the cerebral ganglia, and in three weeks in the pedal ganglia. In juveniles, transient expression of GABA was found in the pedal ganglia (fourth cluster).

Age Factors↗

Combined toxicity of dissolved mercury with copper, lead and cadmium on embryogenesis and early larval growth of the Paracentrotus lividus sea-urchin.

The individual and combined toxicity of dissolved mercury, copper, lead and cadmium has been investigated by using the Parcentrotus lividus sea-urchin embryo-larval bioassay. Embryogenesis success and early larval growth have been recorded after incubation of fertilised eggs in seawater, both with single metals and binary combinations of Hg with every other metal. For individual metals the ranking of toxicity was Hg > Cu > Pb > Cd, with EC50 values of 21.9, 66.8, 509 and 9240 micrograms/l, respectively. Lowest observed effect concentrations (LOEC) for early larval growth were approximately three times lower than the EC50 values for Hg, Cu and Pb, and more than two orders of magnitude lower for Cd, emphasizing the danger of underestimating toxicity when only lethal effects are recorded. Marking & Dawson's additive indices ranged from 0.10 to 0.19, indicating additive effects with a slight trend to synergism, which was statistically significant for the Hg-Pb combination only. Hayes' additive indices were within the margins considered acceptable to describe additive interactions.

Animals↗

The effects of elutriates from PAH and heavy metal polluted sediments on Crassostrea gigas (Thunberg) embryogenesis, larval growth and bio-accumulation by the larvae of pollutants from sedimentary origin.

The release, bio-availability and toxicity of contaminants, when sediments are resuspended have been examined, studying concurrently their effects on the embryogenesis and on the larval growth of the Crassostrea gigas larvae and their bio-accumulation in those organisms. Three characteristic sediments have been selected (one contaminated by PAHs, a second by heavy metals and the last by the both pollutants). The organisms were directly exposed to elutriates obtained from each sediment or fed on algae (Isochrysis galbana) contaminated with the same elutriates. The elutriates used in this study show contamination levels similar to those observed in some polluted coastal and estuary environments. The larval growth test has appeared to be more sensitive that the embryotoxicity test. The biological effects and the contaminant bio-accumulation were more pronounced when larvae were directly exposed to different elutriates. In the case of PAHs, the contamination of algae was sufficient to lead to effect on the larval growth of the Crassostrea gigas. In all cases, a fraction of contaminants adsorbed on suspended particles was bio-available and accumulated by the larvae. This study has shown that resuspending polluted sediments constitutes a threat to pelagic organisms and than the C. gigas larval growth may be proposed as a test to protect the most sensitive areas.

Animals↗

Transition of Xwnt-11 mRNA from inactive form to polyribosomes in frogs during early embryogenesis.

The distribution of Xwnt-11 mRNA between polysomes and informosomes was studied in Xenopus laevis and Rana temporaria during early embryogenesis. The ratio between polysomes and informosomes suggests their involvement in translation of these mRNAs. In eggs and immediately after fertilization the Xwnt-11 mRNAs are mostly positioned in informosomes. During the cleavage stage, these mRNAs have also been recognized in polysomes. Just before the onset of zygote genome functioning (at the stage of mid blastula), Xwnt-11 mRNA rapidly appears in polysomes of Rana embryos. However, in Xenopus, Xwnt-11 mRNA appears in polysomes only at the end of gastrula. Before this stage, the Xwnt-11 mRNA in Xenopus can be found mostly in informosomes.

Animals↗

Structure, organization and expression of two closely related novel Lea (late-embryogenesis-abundant) genes in Arabidopsis thaliana.

We have isolated and sequenced a 9.5 kb genomic region from A. thaliana, located on chromosome 2, which contains two tandemly arranged closely related genes (AtM10 and AtM17) coding for a new family of LEA proteins. The deduced proteins have a molecular mass of 11 and 29 kDa, respectively, are extremely hydrophilic except at their N-termini and share 70% amino acid (aa) identity. A 47 aa motif containing a 6-cysteine domain is present once in AtM10 and four times in AtM17. The short intergenic region, the identical position of the intron and the overall sequence homology suggest that these two genes evolved through a duplication event. This conclusion is supported by the presence of two homologous strictosidine synthase-like (pseudo)genes downstream from AtM17 and AtM10. Expression studies, using AtM10 and AtM17 cDNAs, revealed that both transcripts accumulate exclusively in seeds from late embryogenesis until two days after imbibition. Expression of both genes in young seedlings is repressed during ABA, salt or drought treatment, whereas a cold stress induces the expression of AtM17 only. In situ hybridization revealed that AtM10 transcripts are detected throughout the embryo while those of AtM17 are more localized to cotyledon cells.

Adaptation, Biological↗

The Translocon-Associated Protein beta (TRAPbeta) in zebrafish embryogenesis. I. Enhanced expression of transcripts in notochord and hatching gland precursors.

The normal translocation of nascent polypeptides into the lumen of the endoplasmic reticulum (ER) is thought to be aided in part by a translocon-associated protein (TRAP) complex consisting of 4 protein subunits. The association of mature proteins with the ER and Golgi, or other intracellular locales, such as lysosomes, depends on the initial targeting of the nascent polypeptide to the ER membrane. A similar scenario must also exist for proteins destined for secretion. We have identified a member of the TRAP complex using a two hybrid screen to isolate proteins that bind to zebrafish (Danio) Ran binding protein 1. The polypeptide predicted from the largest open reading frame contains 183 amino acids with a 86 and 87% sequence identity to the TRAPbeta subunits in human and chicken, respectively. Sequence analysis identified a cleavable amino-terminal signal peptide in the zebrafish TRAPbeta subunit and a region of the protein spans the membrane of the endoplasmic reticulum. A reverse transcriptase-polymerase chain reaction assay showed that TRAPbeta mRNA is expressed in the developing zebrafish embryo. TRAPbeta mRNA is maternally supplied to the egg and is expressed constitutively throughout development and in the adult. This pattern of expression indicates that the message encoding part of the machinery targeting nascent polypeptides to the ER lumen is available at the onset of embryogenesis when the rate of translation increases exponentially over that occurring in the oocyte. In situ hybridization was used to test whether or not TRAPbeta transcripts might become localized and/or enriched in the developing embryo. Homogeneous staining is seen in the blastula and early gastrula stages. At mid-to-late gastrula stages, however, the message becomes enriched in the developing notochord and polster, or hatching gland rudiment. The TRAPbeta gene, mapped using the LN54 mouse-zebrafish radiation hybrid panel to linkage group 19, resides next to a gene (Z15451) which has sequence homology to notch2 and vascular endothelial growth factor. TRAPbeta, however, does not appear to belong to a group of genes which are syntenic with orthologues or paralogues on human chromosomes.

Amino Acid Sequence↗