Biomedical subjects

T Ueki

Publications and source records attributed to T Ueki.

At least 55 records · Page 3Linked to original sources

PubMed1999

CD95 ligand expression enhances growth of murine renal cell carcinoma in vivo.

The CD95/CD95 ligand (CD95L) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. In this system, two murine CD95L-transfected renca clones and a control renca clone transfected only with the vector were implanted into the subcapsule of the left kidney of Balb/c and Balb/c nude mice. Both CD95L-expressing and control renca clones formed macroscopic tumors in all of the Balb/c and Balb/c nude hosts 14 days after implantation. Growth of tumors of murine CD95L-transfected renca cells was significantly better than that of control renca cells in Balb/c mice, while the growth advantage of CD95L transfectants was not observed in Balb/c nude mice. Lymphocytes underwent apoptosis mainly in the periphery of the CD95L-expressing tumors but not in control tumors grown in Balb/c mice, while lymphocytes undergoing apoptosis were not observed in CD95L-expressing tumors or in control tumors grown in Balb/c nude mice. Neutrophilic recruitment was rarely observed in CD95L-expressing or control tumors. CD95L expressed on renca cells possibly suppressed immune responses against renca tumors by inducing apoptosis of the infiltrating lymphocytes. However, CD95L-expressing renca cells did not form tumors in the renal subcapsule of allogeneic C3H/HeJ mice.

Animals↗

PubMed1999

Semiquantitative evaluation of alpha1A-adrenoceptor subtype mRNA in human hypertrophied and non-hypertrophied prostates: regional comparison.

The main purpose of this study was to compare semiquantitatively the amount of alpha1a-adrenoceptor subtype mRNA in urethral, central and peripheral areas in benign hypertrophied prostates and non-hypertrophied prostate by the competitive reverse transcriptase polymerase chain reaction (RT-PCR) method. Prostates from twenty cases of men with benign prostatic hypertrophy (BPH) and 5 cases of bladder tumor without BPH were obtained for this study. The mRNA was extracted from the urethral, central and peripheral areas of each prostate, and quantitative RT-PCR was performed using the ratio of PCR product of alpha1a-adrenoceptor mRNA/beta2-microglobulin mRNA. The ratio for the central area of the hypertrophied prostate was significantly greater than that for the same area of the non-hypertrophied prostate (p < 0.05). In contrast, the urethral area showed no significant difference between the two prostate conditions. The central area of the hypertrophied prostate showed the tendency to have an increased alpha1a-adrenoceptor mRNA level compared with the urethral area, though no statistical difference was recognized because of the high standard error. Regional differences in the alpha1a-adrenoceptor mRNA in the non-hypertrophied prostate were rarely observed. The present finding demonstrates that the increased alpha1a-adrenoceptor mRNA content found in the hypertrophied prostate (1) was due to that in the central area.

Aged↗

PubMed1999

Hepatocyte growth factor promotes migration of human hepatocellular carcinoma via phosphatidylinositol 3-kinase.

Hepatocyte growth factor (HGF) is known to be a potent mitogen and motogen for epithelial cells. Hepatocellular carcinoma (HCC) often metastasizes, and the c-Met/HGF receptor is highly expressed by HCC cells. The aim of this study was to investigate the signaling pathways associated with the motogenic effect of HGF on HCC cells via c-Met. HCC cell lines (Hep3B, HepG2, PLC, and Huh-7) and HCC cells harvested from patients were used for the Boyden chamber assay of chemotactic activity as well as for immunoprecipitation and immunoblotting studies. HGF stimulated the motility of Hep3B, HepG2, and Huh-7 cells in a dose-dependent manner in association with tyrosine phosphorylation of c-Met and activation of phosphatidylinositol 3-kinase (PI3-K). A tyrosine kinase inhibitor (genistein) and a PI3-K inhibitor (wortmannin) prevented the migration of HCC cells. However, migration was not prevented by calphostin C, an inhibitor of protein kinase C (PKC), which is a downstream target of phospholipase Cgamma (PLCgamma). HGF also stimulated the migration of HCC cells obtained from three patients, while wortmannin prevented the migration of these cells. These results indicate that HGF stimulates the migration of HCC cells through the tyrosine phosphorylation of c-Met via activation of PI3-K.

Androstadienes↗

PubMed1999

Hepatocyte growth factor gene therapy of liver cirrhosis in rats.

Liver cirrhosis is the irreversible end result of fibrous scarring and hepatocellular regeneration, characterized by diffuse disorganization of the normal hepatic structure of regenerative nodules and fibrotic tissue. It is associated with prominent morbidity and mortality, and is induced by many factors, including chronic hepatitis virus infections, alcohol drinking and drug abuse. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, shows mitogenic, motogenic and morphogenic activities for a wide variety of cells. Moreover, HGF plays an essential part in the development and regeneration of the liver, and shows anti-apoptotic activity in hepatocytes. In a rat model of lethal liver cirrhosis produced by dimethylnitrosamine administrations, repeated transfections of the human HGF gene into skeletal muscles induced a high plasma level of human as well as enodogenous rat HGF, and tyrosine phosphorylation of the c-Met/HGF receptor. Transduction with the HGF gene also suppressed the increase of transforming growth factor-beta1 (TGF-beta1), which plays an essential part in the progression of liver cirrhosis, inhibited fibrogenesis and hepatocyte apoptosis, and produced the complete resolution of fibrosis in the cirrhotic liver, thereby improving the survival rate of rats with this severe illness. Thus, HGF gene therapy may be potentially useful for the treatment of patients with liver cirrhosis, which is otherwise fatal and untreatable by conventional therapy.

Animals↗

PubMed1999

Utilization of variant-type of human alpha-fetoprotein promoter in gene therapy targeting for hepatocellular carcinoma.

We previously reported that the retroviral vector (LNAFW0.3TK) expressing the herpes simplex thymidine kinase (HSVtk) gene under the control of the 0.3 kb human alpha-fetoprotein (AFP) promoter provided the ganciclovir (GCV)-mediated cytotoxicity in the high AFP-producing (HuH-7) but not in the low AFP-producing (huH-1/cl.2) human hepatoma cells. In the present study, we constructed the retroviral vector (LNAFM0.3TK) in which the HSVtk gene expression is regulated by the variant-type of the 0.3 kb human AFP promoter with a G-to-A substitution at nucleotide -119, a point mutation responsible for hereditary persistence of human AFP and the vector was applied to three human hepatoma cell lines HuH-7, huH-1/cl.2 and intermediate AFP-producing cells (PLC/PRF/5). By the reporter gene transfection assay, the activity of the variant-type of the promoter was much higher than that of the wild-type of the promoter in both HuH-7 and huH-1/cl.2 cells. Consistent with this, LNAFM0.3TK infection could sensitize huH-1/cl.2 cells, as well as HuH-7 and PLC/PRF/5 cells to GCV, but did not affect cell growth of nonhepatoma cells (HeLa). In addition, the bystander effect was achieved more efficiently by LNAFM0.3TK infection than LNAFW0.3TK infection in HuH-7 cells. These results suggest that the variant-type of the human AFP promoter ensures the therapeutic gene expression in gene therapy particularly for the low AFP-producing hepatoma cells.

Carcinoma, Hepatocellular↗

PubMed1999

Effect of Bcl-2 overexpression in human prostate cancer cells in vitro and in vivo.

BACKGROUND: Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti-apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl-2 and its family members are best characterized. METHODS: To investigate the effect of bcl-2-mediated anti-apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl-2 (LNCaP/bcl-2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl-2 was compared with the parental cell line in vitro and in vivo. RESULTS: LNCaP/bcl-2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum-free or androgen-free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum-free or androgen-free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl-2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl-2-derived tumors showed resistance, as was previously reported. CONCLUSIONS: These data confirm the notion that anti-apoptotic function of bcl-2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.

Androgens↗

PubMed1999

PTEN/MMAC1 mutations in hepatocellular carcinomas: somatic inactivation of both alleles in tumors.

Allelic loss of loci on chromosome 10q occurs frequently in hepatocellular carcinomas. Somatic mutations of the PTEN/MMAC1 gene on this chromosome at 10q23 were recently identified in sporadic cancers of the uterus, brain, prostate and breast. To investigate the potential role of PTEN/MMAC1 gene in the genesis of hepatocellular carcinomas, we examined 96 tumors for allelic loss on 10q and also for subtle mutations anywhere within the coding region of PTEN/MMAC1 gene. Allelic loss was identified in 25 of the 89 (27%) tumors that were informative for polymorphic markers in the region. Somatic mutations were identified in five of those tumors: three frameshift mutations, a 1-bp insertion at codon 83-84 in exon 4 and two 4-bp deletions, both at codon 318-319 in exon 8; two C-to-G transversion mutation, both at -9 bp from the initiation codon in the 5' non-coding region of exon 1. No missense mutation was observed in this panel of tumors. In most of the informative tumors carrying intragenic mutations of one allele, we were able to detect loss of heterozygosity as well. These findings suggest that two alleles of the PTEN/MMAC1 gene may be inactivated by a combination of intragenic point mutation on one allele and loss of chromosomal material on the other allele in some of these tumors.

Alleles↗

PubMed1999

Diagnosis of the nutcracker syndrome with color Doppler sonography: correlation with flow patterns on retrograde left renal venography.

OBJECTIVE: Our objective was to confirm flow patterns of the left renal vein and assess the usefulness of color Doppler sonography in the diagnosis of the renal vein entrapment, or nutcracker, syndrome. SUBJECTS AND METHODS: Forty-four patients with hematuria of unknown origin underwent color Doppler sonography, renal arteriography, retrograde left renal venography, and renocaval pressure measurement. The flow patterns were classified according to the presence or absence of distended left renal veins on sonograms and collateral veins on retrograde venograms. The sensitivity and specificity of color Doppler sonography for revealing the nutcracker syndrome were assessed by analyzing pressure gradients in combination with the venograms, which were used as the gold standard. RESULTS: Twenty-one nondistended left renal veins were seen, including 19 (43%) without collateral veins or hypertension and two (5%) with collateral veins but without hypertension (long-term nutcracker syndrome). The 23 distended left renal veins included seven without collateral veins or hypertension and one with hypertension but without collateral veins (early nutcracker syndrome). The remaining 15 distended left renal veins with collateral veins included 11 (25%) with borderline hypertension (partially compensatory status of the syndrome) and four (9%) with hypertension (noncompensatory status of the syndrome). The sensitivity and specificity of color Doppler sonography for revealing the nutcracker syndrome were 78% and 100%, respectively, when color flow in collateral veins was included in the diagnostic criteria. CONCLUSION: The nutcracker syndrome can exist in either nondistended or distended left renal veins. However, normal flow also can exist in distended left renal veins. The ability of color Doppler sonography to reveal color flow in collateral veins is useful for the noninvasive diagnosis of the nutcracker syndrome.

Adolescent↗

PubMed1999

Glucolipsin A and B, two new glucokinase activators produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii.

During the screening of the natural products for their ability to increase the activity of glucokinase by relieving inhibition by long chain fatty acyl CoA esters (FAC), two novel compounds, glucolipsin A (1) and B (2) were isolated from the butanol extracts of Streptomyces purpurogeniscleroticus WC71634 and Nocardia vaccinii WC65712, respectively. The structures of these two compounds were established by spectroscopic methods and chemical degradation. Glucolipsin A (1) and B (2) relieved the inhibition of glucokinase by FAC with RC50 values of 5.4 and 4.6 microM.

Disaccharides↗

PubMed1999

[Tubeless cutaneous ureterostomy through a single stoma with new extraperitoneal ureteral route up to stoma].

Tubeless cutaneous ureterostomy through a single stoma has been said to be difficult to establish in patients with normal ureters or normal ureters combined with thick fatty abdominal wall, because of the poor blood supply at the end of the ureters. The technical improvements observed were as follows: 1) The peritoneal fold and the upward traction of the gonadal vessels decrease the ureteral tension and keep the blood supply to the ureters in the extraperitoneal approach. 2) The gonadal vessels and its surrounding tissue, covering the subcutaneous fatty tissue, help the ureteral adhesion at the anastomotic site. 3) Full diminution of the skin defect caused by flap formation, decreases the horizontal tension of the side-to-side anastomized ureters. Sixteen patients with normal ureters underwent this procedure. In a short-term (4-37 months) observation, 4 of the patients, including one with thick abdominal fat, showed unilateral hydronephrosis and 2 patients unilateral non-function kidney. The remaining 10 patients had no complications. Moreover, all the patients have kept their ureterostomies tubeless and their serum blood urea nitrogen and creatinine levels were within normal limits except for one patient. It is reasonably concluded that the new method will result in success clinically even in patients with normal ureters and thick abdominal fatty tissue.

Aged↗

PubMed1998

Trichromatic Concept at SPring-8 RIKEN Beamline I.

SPring-8 RIKEN beamline I has been designed and developed for structural biology research by the Institute of Physical and Chemical Research (RIKEN). The beamline consists of two experimental stations for protein crystallography and small-angle X-ray scattering. Both types of experiments can be carried out simultaneously, with dichromatic synchrotron radiation emitted from two coaxial undulators with vertical polarization. The branched beams are generated by a transparent diamond crystal. With synchrotron radiation, the multiple-wavelength anomalous-dispersion (MAD) method, which gives phases from a single anomalous scatterer, has been developed. Anomalous scattering contributes a small proportion of the diffraction intensity so that the accuracy of intensity data is important. The protein crystallography branch of RIKEN beamline I has been designed based on a 'trichromatic concept' to optimize MAD data collection. This concept requires the quasi-simultaneous collection, by use of a 'trichromator', of three intensity data sets at three different wavelengths from a single protein crystal without changing any settings. The main feature of the concept is the minimization of systematic errors in the measurement of anomalous diffraction for the MAD method. Initial commissioning of the beamline has provided three different monochromated undulator beams, which were successfully observed on the phosphor screen located at the near end of the trichromator.

Journal Article↗

PubMed1998

Early development of the peripheral nervous system in a lancelet species.

The developmental pattern of the lancelet (amphioxus) peripheral nervous system from embryos to larvae has been studied by using wholemount immunostaining and transmission electron microscopy. The peripheral nerves first appeared on the anterior dorsal surface of the medulla at the middle neurula stage, when the anterior nerve cord was just closing. A single axon with a large growth cone was the progenitor of each nerve. The nerve roots adopted an asymmetric arrangement soon after. The first nerve, likely a pair of pure sensory nerves, sprouted from the anterior tip of the nerve cord. This nerve may be comparable topographically to the preoptic nerve (the posterior branch of the terminal nerve) in lungfishes. However, the neuron that first extends its axon was located in the medulla, as in the other posterior nerves. One of the extramedullary primary sensory neurons, the corpuscles of de Quatrefages, appeared in larvae with the mouth and two anterior gill pores. Their axons were seemingly fasciculated with the efferent axon of the first nerve. The second nerve, the most complex one to appear during embryonic and early larval development, innervated the preoral pit and the buccal region. The third and fourth nerves on the left side also innervated the buccal region. The larval innervation patterns in the anterior region differed from the adult organization, suggesting a segmental rearrangement of the nerve supply during development. There was no evidence to dichotomize the peripheral nerves into cranial and spinal nerves, as exist in vertebrates. These characteristics of the peripheral nervous system in the lancelet indicate that this animal has a rather derived or primitive developmental system of peripheral nerves, making the analysis of homology with vertebrates difficult.

Animals↗

PubMed1998

Expression of a twist-related gene, Bbtwist, during the development of a lancelet species and its relation to cephalochordate anterior structures.

Mesoderm formation plays a crucial role in the establishment of the chordate body plan. In this regard, lancelet embryos develop structures such as the anteriorly extended notochord and the lateral divertecula in their anterior body. To elucidate the developmental basis of these structures, we examined the expression pattern of a lancelet twist-related gene, Bbtwist, from the late gastrula to larval stages. In late-gastrula embryos, the transcripts of Bbtwist were detected in the presumptive first pair of somites and the middorsal wall of the primitive gut. The expression of Bbtwist was then upregulated in the lateral wall of somites and the notochord. At the late-neurula stage, it was also expressed in the anterior wall of the primitive gut, as well as in the evaginating lateral diverticula. No signal was detected in the left lateral diverticulum when it was separated from the gut, while in the right one, the gene was expressed later during the formation of the head coelom in knife-shaped larvae, and in the anterior part of the notochord in the same larvae. In 36-h larvae, only faint expression was detected in the differentiating notochordal and paraxial mesoderm in the caudal region. These expression patterns suggest that Bbtwist is involved in early differentiation of mesodermal subsets as seen in Drosophila and vertebrates. The expression in the anterior notochord may be related to its anterior expansion. The expression in the anterior wall of the primitive gut and its derivative, the lateral diverticula, suggests that lancelets share the capability to produce a mesodermal population from the tip of the primitive gut with nonchordate deuterostome embryos.

Amino Acid Sequence↗

PubMed1998

Stereotyped axonal bundle formation and neuromeric patterns in embryos of a cyclostome, Lampetra japonica.

Early embryonic development of the nervous system of a lamprey, Lampetra japonica, was studied by using immunohistochemical techniques and by scanning electron microscopy. The earliest appearance of axons was detected at Tahara's stage 21-, when dorsolateral and ventral longitudinal fasciculi were present in the hindbrain and spinal cord regions. The branchiomeric nerve roots began to appear at stage 22; the fibers were joined to the dorsolateral fasciculus proximally and also extended distally into each pharyngeal arch. The anterior neural tube was divided into several neuromeres: the mid-hindbrain sulcus became apparent first, then the portion rostral to this sulcus was subdivided into two portions by the syn-parencephalic boundary. In the hindbrain around stage 23, rhombomeres developed transiently, of which, rhombomere 4 was the most distinctive. Putative crest cells forming the octavofacial nerve root anlage were selectively adhering to rhombomere 4, whereas no crest cells were found on rhombomere 3. The assignment of the crest-derived nerve anlage to rhombomeres is conserved between gnathostomes and L. japonica. The neuromerical scheme of the neural tube of L. japonica is also mostly in accordance with that in gnathostomes, sharing the basic developmental patterning of axon bundles at early developmental stages. The most distinct difference between these two groups is the topographical relationships between the hindbrain neuraxis and pharyngeal arches, as well as the otic placode.

Acetylation↗

PubMed1998

Telomerase activity in hepatocellular carcinoma and adjacent liver tissues.

BACKGROUND AND OBJECTIVES: Activation of telomerase and stabilization of telomeres are considered necessary for immortalization of tumor cells. Telomerase activity was analyzed in 69 hepatocellular carcinomas and adjacent chronic liver disease tissues. The telomerase activity level was examined in relation to clinicopathologic features. METHODS: Telomerase activity was determined by a telomeric repeat amplification protocol. Immature and mature leukocytes were removed from homogenized tissue of adjacent livers using anti-CD45 and anti-CD15 monoclonal antibody-coated magnetic beads. RESULTS: Telomerase activity was detected in hepatocellular carcinomas and leukocytes, but not in liver cells from adjacent chronic liver disease tissues after the separation of leukocytes. All hepatocellular carcinomas displayed telomerase activity, and the activity level correlated with the degree of differentiation (P=0.021) and patient survival (P=0.039). CONCLUSIONS: These results indicate that activation of telomerase may be required as a critical step in hepatocarcinogenesis and tumor development, and detection of telomerase activity with removal of contaminating leukocytes may be useful in the characterization or prognostication of hepatocellular carcinoma.

Adult↗

PubMed1998

Rostral truncation of a cyclostome, Lampetra japonica, induced by all-trans retinoic acid defines the head/trunk interface of the vertebrate body.

The effect of all-trans retinoic acid on embryogenesis was studied in a cyclostome, Lampetra japonica. Treatment with 0.05-0.5 microM retinoic acid on early gastrula and early neurula resulted in loss of the pharynx and in the rostral truncation of the neural tube. The mouth, pharynx, esophagus, heart, endostyle, and rostral brain were missing with graded severity. In the severest case, the embryo consisted only of trunk segments, especially myotomes that extended to the rostral end of the axis. The effect appeared to be dose- and stage-dependent: Rostral pharyngeal arches were more vulnerable to a lower amount of retinoic acid, and earlier treatment resulted in severer defects. The initial protrusion of the anterior axis started equally in control and retinoic acid-treated embryos, implying that the head morphogenesis is omitted in treated embryos. By identifying the number of myotomes based on the differentiation of hypobranchial muscles, there seemed to be no myotomes lost by retinoic acid-induced truncation. The rostral truncation, therefore, was not simply a limitation of the anterior axis but was restricted to the ventral portion; only the branchial arches disappeared with normally developing myotomes dorsally. The absent region can be defined as the vertebrate head in a morphological sense, including the branchiomeric and preotic paraxial regions as well as the heart. The results suggest the presence of distinct programs between somitomeric and branchiomeric portions of the body, providing a developmental basis for the dual-metamerical body plan of vertebrates.

Animals↗

PubMed1998

Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma.

Mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) is a key molecule in intracellular signal transducing pathways that transport extracellular stimuli from cell surface to nuclei. MAPK/ERK has been revealed to be involved in the physiological proliferation of mammalian cells and also to potentiate them to transform. However, its role in the outgrowth of human hepatocellular carcinoma (HCC) has yet to be clarified. Therefore, in this study, we investigated the activation of MAPK/ERK and its associated gene expression in HCC. MAPK/ERK was activated in 15 of 26 cases of HCC we examined (58%), and its activity level was significantly higher in HCC than in the adjacent non-cancerous lesions. Besides, MAPK/ERK activation in HCC was positively correlated with protein expression of transcription factor c-Fos. Furthermore, in 25 of 26 cases of HCC which genomic DNA was available, 22 cases without genomic DNA amplification exhibited positive correlation, not only between protein expression of c-Fos and cyclin D1, but also between MAPK/ERK activation and cyclin D1 expression. Concerning the relationship between MAPK/ERK activation and the clinicohistopathological features of HCC, the tumor (HCC) versus non-tumor (non-cancerous counterpart) ratio (T/N) of MAPK/ERK activity was positively correlated with tumor size, but neither with the stage of HCC nor the degree of differentiation of HCC. In conclusion, these findings suggest that MAPK/ERK activation in human HCC may play an important role in multistep hepatocarcinogenesis, especially in the progression of HCC; at least in part, through cyclin D1 up-regulation primarily induced by MAPK/ERK via c-Fos.

Aged↗

PubMed1998

Otx cognates in a lamprey, Lampetra japonica.

Gnathostomes have two lineages of Otx genes, Otx1 and Otx2, as cognates of a Drosophila head gap gene, orthodenticle. Previous studies with mutant mice have demonstrated that they play essential roles in the development of rostral head. To shed lights on the evolution of the rostral head in vertebrates we isolated their cognates in the Japanese marine lamprey, Lampetra japonica. The lamprey genome appeared to have two Otx cognantes, LjOtxA and LjOtxB. Phylogenetic analyses suggest that LjOtxA clusters with gnathostome Otx2 genes, but LjOtxB does not belong to either the Otx1 or Otx2 lineage. LjOtxA was expressed in the forebrain and midbrain with the caudal limit possibly at the midbrain/hindbrain junction as gnathostome Otx cognates are, but LjOtxB was not expressed in the brain. No Otx1 or Otx2 cognates are known in gnathostomes that are not expressed in the brain. Both LjOtxA and LjOtxB were expressed in the olfactory placode, epiphysis, optic stalks, and lower and upper lips. LjOtxB was also expressed in the eyes, where no LjOtxA transcripts were detected. Thus, Otx1 and Otx2 functions for the development of forebrain and midbrain in gnathostomes appear to be shouldered by LjOtxA alone in the lamprey. LjOtxB may have diverged from the stem of the Otx1 and Otx2 lineages and evolved independently.

Amino Acid Sequence↗