Publications by authors named "Jin-Hu Wang"

16 Publications

  • Page 1 of 1

Standards of care for Kasabach-Merritt phenomenon in China.

World J Pediatr 2021 Apr 26;17(2):123-130. Epub 2020 Aug 26.

Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Kasabach-Merritt phenomenon (KMP) is a rare disease that is characterized by severe thrombocytopenia and consumptive coagulation dysfunction caused by kaposiform hemangioendothelioma or tufted hemangioma. This condition primarily occurs in infants and young children, usually with acute onset and rapid progression. This review article introduced standardized recommendations for the pathogenesis, clinical manifestation, diagnostic methods and treatment process of KMP in China, which can be used as a reference for clinical practice.
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http://dx.doi.org/10.1007/s12519-020-00379-9DOI Listing
April 2021

Paraplegia after transcatheter artery chemoembolization in a child with clear cell sarcoma of the kidney: A case report.

World J Clin Cases 2020 Jun;8(11):2332-2338

Department of Surgical Oncology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310053, Zhejiang Province, China.

Background: Transcatheter arterial chemoembolization (TACE) is a common treatment for inoperable malignant renal tumors. However, a series of complications may follow the TACE treatment. Spinal cord injury caused by the embolization of intercostal or lumbar arteries is extremely rare.

Case Summary: We describe a case with quite uncommon spinal cord injury after TACE in a 3-year-old child with clear cell sarcoma of the kidney. Sensory impairment beneath the T10 dermatomes and paraplegia on the day after TACE were found in this patient. Unfortunately, sustained paraplegia still existed for more than 2 mo after TACE despite the large dose of steroids and supportive therapy.

Conclusion: We should draw attention to an uncommon complication of paraplegia after TACE treatment in malignant renal tumors. Although it is rare, the result is disastrous.
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http://dx.doi.org/10.12998/wjcc.v8.i11.2332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281067PMC
June 2020

Unusual presentation of bladder neuroblastoma in a child: A case report.

World J Clin Cases 2020 Jan;8(1):194-199

Department of Radiology, Children's Hospital, Zhejiang University School of Medicine, ; National Clinical Research Center for Child Health, Hangzhou 310053, Zhejiang Province, China.

Background: Neuroblastoma is an extracranial malignant tumor in children that is most often located in the adrenal gland and sympathetic ganglion. Here, we present a rare case of neuroblastoma originating from the urinary bladder.

Case Summary: A 3-year-old girl presented with lower abdominal pain with micturition. Ultrasound revealed a lower abdominal mass. Abdominal computed tomography scan displayed a solitary mass at the top of the urinary bladder. Blood levels of neuron-specific enolase and lactate dehydrogenase were elevated. We treated the child with partial cystectomy and six courses of chemotherapy, and the outcome at 4-year follow-up was unremarkable.

Conclusion: Neuroblastoma should be considered when tumors are located in the urinary bladder, especially in the dome; although this presentation is rare, the prognosis is very good.
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http://dx.doi.org/10.12998/wjcc.v8.i1.194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962065PMC
January 2020

A recombinant measles virus vaccine strain rMV-Hu191 has oncolytic effect against human gastric cancer by inducing apoptotic cell death requiring integrity of lipid raft microdomains.

Cancer Lett 2019 Sep 19;460:108-118. Epub 2019 Jun 19.

Zhejiang University School of Medicine, Hangzhou, 310000, Zhejiang, China; Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310052, Zhejiang, China; Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, 310052, Zhejiang, China. Electronic address:

Live-attenuated strain of measles virus (MV) has oncolytic effect. In this study, the antitumor effect of rMV-Hu191, a recombinant Chinese Hu191 MV generated in our laboratory by efficient reverse genetics system, was evaluated in gastric cancer (GC). From our data, rMV-Hu191 induced cytopathic effects and inhibited tumor proliferation both in vitro and in vivo by inducing caspase-dependent apoptosis. In mice bearing GC xenografts, tumor size was reduced and survival was prolonged significantly after intratumoral injections of rMV-Hu191. Furthermore, lipid rafts, a type of membrane microdomain with specific lipid compositions, played an important role in facilitating entry of rMV-Hu191. Integrity of lipid rafts was required for successful viral infection as well as subsequent cell apoptosis, but was not required for viral binding and replication. CD46, a MV membrane receptor, was found to be partially localized in lipid rafts microdomains. This is the first study to demonstrate that Chinese Hu191 MV vaccine strain could be used as a potentially effective therapeutic agent in GC treatment. As part of the underlying cellular mechanism, the integrity of lipid rafts is required for viral entry and to exercise the oncolytic effect.
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http://dx.doi.org/10.1016/j.canlet.2019.06.010DOI Listing
September 2019

Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for treatment of clear cell sarcoma of the kidney in children.

J Pediatr Surg 2019 Mar 2;54(3):550-556. Epub 2018 Oct 2.

Department of Radiology, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China. Electronic address:

Background: Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children.

Methods: Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2 years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy.

Results: No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5 months (range, 11-83 months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases.

Conclusions: Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study.

The Type Of Study: A case series with no comparison group.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1016/j.jpedsurg.2018.09.012DOI Listing
March 2019

A highly malignant case of neuroblastoma with substantial increase of single-nucleotide variants and normal mismatch repair system: A case report.

Medicine (Baltimore) 2017 Dec;96(50):e8845

Departments of Central Laboratory, Pathology, Oncology and Radiology, The Children's Hospital of Zhejiang University School of Medicine Institute of Translational Medicine, Zhejiang University The Key Laboratory of Diagnosis and Treatment of Neonatal Diseases of Zhejiang Province, Hangzhou, Zhejiang, China.

Rationale: Neuroblastoma is a common abdominal malignancy in children. The chemoresistant and relapsed cases have poor prognosis. The genetic background and the mechanism of resistance remain unelucidated. Next-generation sequence (NGS) is becoming a popular tool to unravel the genetic background and to guide precision medicine in oncology studies as well as in clinical practice.

Patient Concerns: Here we report a neuroblastoma case of a boy aged 2 years and 8 months when first diagnosed, with multiple metastatic sites found in both lungs. The metastatic tumors were resistant to chemotherapy and the patient suffered from severe bone marrow suppression. NGS of the whole exon revealed somatic mutations including 9666 single-nucleotide variants (SNVs) from 5148 genes, 55 copy number variations (CNVs), and 140 insertion-deletion variations. The high frequency of SNVs makes it distinguished case. However, no mutation of key tumor driver genes with functional significance was identified. No abnormality was found in nucleic acid synthesis enzymes. No amplification of c-Myc and n-Myc was found by fluorescence in situ hybridization (FISH). Both NGS and immunohistochemistry (IHC) analysis indicated that DNA mismatch repair (MMR) system was intact.

Interventions: After initial diagnosis, the patient received combinational chemotherapy, which includes vindesine, an analogue of adriamycin suggested by NGS data, for 4 months. Radical section of the tumor together with the left kidney and the left adrenal gland was performed 5 months after diagnosis. Postsurgical chemotherapy protocols was similar with the previous.

Outcomes: The patient died 2 years after initial diagnosis after 8 relapses following combinational chemotherapy.

Lessons: This case of neuroblastoma is with pronounced somatic mutations but unidentified driver gene and therapeutic target. Although NGS is a potentially powerful tool to guide precision medicine, at current stage, its application in the clinic certainly has its limits. The underlying mechanism of the substantially increased SNV number, as well as the malignant behaviors of the tumor, is yet to be revealed.
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http://dx.doi.org/10.1097/MD.0000000000008845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815686PMC
December 2017

Sinomenine Hydrochloride Attenuates Renal Fibrosis by Inhibiting Excessive Autophagy Induced by Adriamycin: An Experimental Study.

Evid Based Complement Alternat Med 2017 17;2017:6878795. Epub 2017 Jul 17.

Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.

The objective of this study is to investigate if sinomenine hydrochloride (SIN-HCl) could be effective against adriamycin-induced renal fibrosis by regulating autophagy in a rat model. Forty male Sprague-Dawley (SD) rats were randomly divided into control group, model group, telmisartan group, and SIN-HCl group; rat model was induced by adriamycin; all rats were given intragastric administration for 6 weeks. Urine was collected from rats in metabolic cages to determine 24 h protein level. This was done after intragastric administration for the first two weeks and then once for every two weeks. Renal pathological changes were examined by the staining of HE, Masson, and PASM. Expressions and distributions of fibronectin (FN), laminin (LN), light chain 3 (LC3), and Beclin-1 were observed by immunohistochemistry. SIN-HCl ameliorates proteinuria, meanwhile attenuating the renal pathological changes in adriamycin-induced rats and also attenuating renal fibrosis and excessive autophagy by reducing the expression of FN, LN, LC3, and Beclin-1. SIN-HCl attenuates renal fibrosis by inhibiting excessive autophagy induced by adriamycin and upregulates the basal autophagy.
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http://dx.doi.org/10.1155/2017/6878795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535740PMC
July 2017

Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance.

Curr Cancer Drug Targets 2018 ;18(3):295-303

Departments of Central Laboratory, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Background: Autophagy is a physiological pathway characterized by lysosomedependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy. The role of autophagy in nephroblastoma is largely uninvestigated.

Objective: This study is to investigate the change of autophagy level in nephroblastoma, and whether autophagy could be a therapeutic target in anaplastic nephroblastoma.

Method: In clinical samples of childhood nephroblastoma, autophagy activity was evaluated by the expressions of selected autophagy markers as well as the presence of autophagosome ultrastructure. Use of autophagy inhibitors alone and in combination with conventional chemotherapeutics, was studied both in vivo and in vitro.

Results: In nephroblastoma, there was decrease in the Beclin 1 level and the number of autophagosomes, suggesting autophagy inhibition. Furthermore, in two anaplastic nephroblastoma cell lines, G401 and SK-NEP1, autophagy inhibitors further enhanced the efficacy of conventional chemotherapeutics including vincristine and cisplatin. In G401 tumor model established in nude mice, combinational use of chloroquine, an inhibitor of autophagy degradation, further decreased the tumor mass compared with single use of the chemotherapeutics vindesine, although no statistical significance was achieved.

Conclusion: Our results suggest that autophagy deregulation is involved in nephroblastoma, and targeting autophagy can serve as a potential adjuvant strategy for the highly malignant cases.
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http://dx.doi.org/10.2174/1568009617666170330105433DOI Listing
April 2019

Neoadjuvant Intraarterial Chemotherapy for Treatment of Malignant Vaginal Tumors in Children: A Single-Center Experience.

J Vasc Interv Radiol 2016 Jul;27(7):996-1000

Pediatric Surgery, Children's Hospital, Zhejiang University School of Medicine, Zhugan Xiang 57, Hangzhou 310003, China; Department of Pediatric Surgery, Children's Hospital, Zhejiang University School of Medicine, Zhugan Xiang 57, Hangzhou 310003, China.

Six patients (aged 3-36 mo) with vaginal tumors (rhabdomyosarcoma and endodermal sinus tumor [EST]; n = 3 each) received intraarterial chemotherapy (IAC) and intravenous chemotherapy. Patients underwent internal iliac artery infusion with cisplatin, pirarubicin, and vindesine. Intravenous chemotherapy with vindesine, ifosfamide, and etoposide was administered after 3 weeks. Vaginal tumors disappeared in all patients after 2 or 3 cycles of alternating therapy. Two patients underwent resection of pelvic metastases. Intravenous consolidation chemotherapy was applied. Four patients were disease-free at a median follow-up of 5.8 years. One patient had pelvic recurrence treated with "salvage" therapy with IAC and surgery and was disease-free for 2.5 years.
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http://dx.doi.org/10.1016/j.jvir.2016.03.025DOI Listing
July 2016

Outcome of children with melamine-induced urolithiasis: results of a two-year follow-up.

Clin Toxicol (Phila) 2013 Jul 4;51(6):473-9. Epub 2013 Jun 4.

Department of Medicine, the Children's Hospital of Zhejiang University School of Medicine and Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Hangzhou, P. R. China.

Objective: Our purpose is to describe the characteristics and the outcome of melamine-induced renal and urinary tract injury in young children who consumed melamine-contaminated infant formula.

Methods: This is a descriptive longitudinal study over 2 years in 240 children with melamine-induced urolithiasis screened in our hospital from September 15 to October 31, 2008. Ultrasonography and serum creatinine (SCr), urea, β2-microglobulin (MG), cystatin C (Cys C), urinary Cr (UCr), microalbumin (mALB), α1-MG, β2-MG, n-acetyl-β-d-glucosaminidase (NAG) and retinol-binding protein (RBP) measurements were performed.

Results: The children ranged in age from 1 to 82 months, and 145 were males. The largest calculus was 33 mm in diameter. X-ray diffraction pattern of the calculi displayed two diffraction peaks at 10.9° and 27.7° (2θ). Surgical management was performed in 14 patients. In 226 patients without surgical management, the calculi were passed in 59.63% patients within 1 month, in 85.40% within 6 and in 91.15% within 24 months. Increased SCr and urea levels were noted in three and six patients, respectively, at the time of diagnosis. The SCr, serum β2-MG, and Cys C levels at the time of diagnosis were higher than those at 3 and 6 months after diagnosis (P < 0.05, respectively). The levels of mALB/UCr, NAG/UCr, and RBP/UCr at the time of diagnosis were higher than those at 3, 6, 12, and 24 months after diagnosis (P < 0.05, respectively). α1-MG/UCr and β2-MG/UCr levels at the time of diagnosis were similar to those at 3 months after diagnosis, and significantly higher than those in the follow-up period (P < 0.05, respectively).

Conclusion: Melamine might injure both the renal glomerulus and the tubule, and that the predominant lesion is urolithiasis. The compositions of melamine-induced urolithiasis are melamine and cyanuric acid crystals. The urolithiasis might persist for over 2 years and cause irreversible damage. Therefore, a long-term follow-up for all patients is required.
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http://dx.doi.org/10.3109/15563650.2013.804191DOI Listing
July 2013

Incidence of pediatric metachronous contralateral inguinal hernia in children aged ≥1 year.

World J Pediatr 2012 Aug;8(3):256-9

Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: The management of the contralateral asymptomatic side when a child with initial unilateral inguinal hernia undergoes herniorrhaphy continues to be controversial. Age less than 6 months at initial herniorrhaphy is considered as a high risk factor of the occurrence of metachronous contralateral inguinal hernia (MCIH). We performed herniorraphy for patients ≥1 year with initial unilateral hernia at one-day-set outpatient-surgery department without any intervention of contralateral groin. In this study, we reviewed the characteristics of development of MCIH in this condition and discuss the management strategies of MCIH.

Methods: The subjects of this study were children who were treated at our outpatient-surgery department from January 2006 to December 2006. A total of 2129 patients with initial unilateral hernia and aged ≥1 year underwent an ipsilateral herniorhhaphy only. Patients were followed up for the development of MCIH to 60 months. The Chi-square test was used for intergroup comparison, a level of P<0.05 was considered as statistically significant.

Results: Among these children 1341 (63.0%) were obtained 60 months follow-up data, 1146 (85.5%) were boys and 195 (14.5%) were girls. MCIH developed in 70 (5.2%) patients, 61 were boys and 9 were girls. In 570 patients aged 12-23 months, 43 developed MCIH (7.5%); in 564 patients aged 24-59 months, 21 developed MCIH (3.7%); and in 207 patients ≥60 months, 6 patients developed MCIH (2.9%), the difference between these groups was highly significant (P=0.004). In male patients, 30 right-sided MCIHs occurred after 423 initial left-sided herniorrhaphies (7.1%) and 31 left-sided MCIHs occurred after 723 initial right-sided herniorrhaphies (4.3%), difference between these two groups was significant (P=0.041). Seventy-seven percent of the MCIHs occurred within 1 year, 94% occurred within 2 years after initial herniorraphy.

Conclusions: As the overall incidence of MCIH in patients aged ≥1 year was 5.2%, routine contralateral groin exploration is not suggested. Transinguinal laparoscopy could be considered as an alternative of conventional "wait and see" policy, especially in patients less than 2 years or left-sided initial unilateral inguinal hernia. If "wait and see" policy is adopted, patients should be closely followed up for 2 years.
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http://dx.doi.org/10.1007/s12519-012-0367-zDOI Listing
August 2012

[Effects of PI3K/Akt signaling pathway on learning and memory abilities in neonatal rats with hypoxic-ischemic brain damage].

Zhongguo Dang Dai Er Ke Za Zhi 2011 May;13(5):424-7

Department of Pediatric Health Care, Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

Objective: To study the effects of PI3K/Akt signaling pathway inhibitor wortmannin on long-term learning and memory abilities in neonatal rats with hypoxic-ischemic brain damage (HIBD).

Methods: Forty-eight neonatal rats were randomly assigned to blank control (n=8), sham-operated (n=8), HIBD model (n=10), HIBD+DMSO (dimethyl sulfoxide, n=8) and HIBD+wortmannin groups (n=8). Wortmannin (2 μL) was injected to the left hippocampus 30 minutes before HIBD inducement in the HIBD+wortmannin group. The Morris water maze test was used to examine the long-term learning and memory abilities at the age of 28 days.

Results: With the increased number of swimming, the escape latency was shortened in various groups. From the second day, the escape latency in the HIBD+wortmannin group was significantly longer than that in the sham-operated and the blank control groups (P<0.05), and the differences increased with the time. On the fourth day, there were significant differences in the escape latency between the HIBD+wortmannin group and the HIBD+DMSO group as well as the HIBD model group (P<0.05). On the eighth day (retention trial), there were the most obvious differences in the escape latency between the HIBD+wortmannin group with the other four groups. In the space exploration test, the number of times crossing the former platform location within 120 seconds after removing the platform in the HIBD+DMSO and the HIBD model group was lower than the sham-operated and the blank control groups (P<0.05). The HIBD+wortmannin group showed lower number of times crossing the former platform location compared with the HIBD+DMSO and the HIBD model groups (P<0.05), as well as the sham-operated and the blank control groups (P<0.01).

Conclusions: P13K/Akt signaling pathway inhibitor wortmannin can aggravate the cognitive impairments, thus affecting adversely long-term learning and memory abilities in neonatal rats with HIBD.
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May 2011

Cloning and analyzing of Xenopus Mespo promoter in retinoic acid regulated Mespo expression.

Acta Biochim Biophys Sin (Shanghai) 2006 Nov;38(11):759-64

Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.

During vertebrate embryogenesis, presomitic mesoderm cells enter a segmental program to generate somite, a process termed somitogenesis. Mespo, a member of the bHLH transcription factor family, plays important roles in this process. However, how Mespo expression is regulated remains unclear. To address this question, we isolated a genomic DNA sequence containing 4317 bp of Mespo 5' flanking region in Xenopus. Luciferase assays show that this upstream sequence has transcription activity. Transgenic assay shows that this genomic contig is sufficient to recapitulate the dynamic stage- and tissue-specific expression pattern of endogenous Mespo from the gastrula to the tailbud stage. We further mapped a 326 bp DNA sequence responding to retinoic acid signaling. These results shed light on how Mespo expression is regulated, and suggest that retinoic acid signaling pathways play roles in somitogenesis through regulating Mespo.
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http://dx.doi.org/10.1111/j.1745-7270.2006.00226.xDOI Listing
November 2006

[Polymorphism and original analysis of mtDNA D-loop of three Leuciscus species in Xinjiang].

Yi Chuan 2003 Jul;25(4):414-8

Bio-engineer College, Shihezi University, Shihezi, Xinjiang 832003, China.

PCR-RFLP technique was employed to amplify about 827bp of mtDNA D-loop hypervariable region of Leuciscus baicalensis, L.merzbacheri and L.idus in Xinjiang. The PCR products of 56 samples with four restriction enzymes were digested: ScaI,HinfI,AluI,DdeI,and RFLP analysis was done then. The study indicates that all of L. species and populations have six haplotypes, L.merzbacheri has two haplotypes: BDAA,BDBA; L.baicalensis has three:AAAA,ABAA,ACAA; L.idus has one:CAAA. It is primarily considered that L.merzbacheri and L.baicalensis have more intra-population mutations. The UPGMA trees with 6 haplotypes and net genetics distance pointed out that L.merzbacheri might be original species, L.baicalensis and L.idus are evolved from L.merzbacheri.
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July 2003

Lef/Tcf-dependent Wnt/beta-catenin signaling during Xenopus axis specification.

FEBS Lett 2003 Jul;547(1-3):1-6

Laboratory of Molecular and Cell Biology, Laboratory of Stem Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yue-yang Road 320, 200031, Shanghai, PR China

Though the Wnt/beta-catenin signaling pathway is known to play key roles during Xenopus axis specification, whether it signals exclusively through Lef/Tcf transcription factors in this process remains unclear. To investigate this issue, we generated transgenic frog embryos expressing green fluorescent protein (GFP) driven by a Lef/Tcf-dependent and Wnt/beta-catenin-responsive promoter. This promoter is highly sensitive and even detects maternal beta-catenin activity prior to the large-scale transcription of zygotic genes. Unexpectedly, GFP expression was observed only in some, but not all, known Wnt/beta-catenin-positive territories in Xenopus early development. Furthermore, ubiquitous expression of dominant Lef-1 protein variants from transgenes revealed that zygotic Lef/Tcf activity is required for the ventroposterior development of Xenopus embryos. In summary, our results suggest that endogenous Wnt/beta-catenin activity does not result in obligatory Lef/Tcf-dependent gene activation, and that the ventroposteriorizing activity of zygotic Wnt-8 signaling is mediated by Lef/Tcf proteins.
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http://dx.doi.org/10.1016/s0014-5793(03)00639-2DOI Listing
July 2003