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PubMed2002

Ectopic pituitary adenoma with malignant transformation.

We report here a case of ectopic pituitary adenoma with malignant transformation after repeated relapses. First, an ectopic pituitary adenoma producing follicle-stimulating hormone was found in the nasal cavity extending to the frontal cranial fossa. Despite repeated surgical resections of the tumor, it recurred three times in 2 years. The tumor gradually showed cellular atypia, mitosis, and necrosis. Immunohistochemical analyses revealed that the expressions of proliferating cell nuclear antigen and MIB-1 increased progressively. Moreover, the expression of p53 was detected at the second recurrence. Finally, at the third recurrence the tumor showed dissemination to the subarachnoid space and multiple metastases in the brain. The patient died of the tumor 10 months after the last resection. These findings indicate that the ectopic pituitary adenoma became malignant. To our knowledge, this is the first report on malignant transformation of ectopic pituitary adenoma. It is important to know that ectopic pituitary adenomas show malignant transformation and that the above parameters (proliferating cell nuclear antigen, MIB-1, and p53) may be useful indicators of the malignant potential of both ectopic and sellar pituitary tumors.

Adenoma↗
PubMed2000

Treatment of ectopic ossification about the elbow.

The surgical treatment of elbow ectopic ossification associated with elbow stiffness has progressed significantly in the past decade. Although previous reports describe inconsistent results and high complication rates, numerous recent reports document not only good results, but also lower complication rates. The current study outlines the authors' treatment of patients with ectopic bone about the elbow. Various modalities have been used for prophylaxis against elbow ectopic ossification in the patient with elbow trauma. However, despite these prophylaxis efforts, periarticular ossification may form and result in disabling elbow stiffness. If ectopic ossification and stiffness develop, operative intervention may be indicated to restore motion. It has been long suggested that operative intervention be delayed for at least 1 year, with earlier intervention thought to predispose to recurrence. Recent reports, however, have documented good results with earlier intervention, from 3 to 6 months after injury. The evaluation of posttraumatic elbow stiffness associated with ectopic ossification is described, followed by a discussion regarding anatomic and functional classifications. Surgery is based on multiple factors including the location of ectopic ossification, the plane(s) of elbow stiffness, and the presence of associated nerve compression. A limited or extended Kocher approach may be used to release most contractures; however, other approaches may be necessary. Surgical technique is described in detail. Meticulous surgical technique is necessary to avoid complications, including triceps avulsion, recurrent elbow stiffness, and hematoma.

Contraindications↗
PubMedDate not supplied

Ectopic prolactinoma on MRI.

OBJECTIVE: We present two patients with ectopic prolactinoma in the sphenoid sinus who were examined by MRI. MATERIALS AND METHODS: Endocrinological evaluations including spontaneous and drug-induced secretion of prolactin (PRL) and MRI features of two patients with ectopic prolactinoma were studied. RESULTS: Both patients had elevated serum PRL levels, and the endocrinological evaluations were similar to those in ectopic prolactinoma. Magnetic resonance of the head revealed a mass occupying the sphenoid sinus with partially empty sella in Case 1 and with normal pituitary gland in Case 2. Ectopic PRL secretion was confirmed by immunocytochemical examination of the ectopic tumor. Case 1 was treated with bromocriptine, leading to marked decrease in serum PRL levels and reduction of tumor size. Transsphenoidal surgery was performed in Case 2, resulting in normalization of serum PRL levels. CONCLUSION: It is necessary to consider ectopic prolactinoma for the differential diagnosis of the sphenoid sinus tumors.

Adult↗
PubMed2002

Ectopic recurrence of craniopharyngioma after an interhemispheric transcallosal approach: case report.

OBJECTIVE AND IMPORTANCE: Ectopic recurrence of a craniopharyngioma is a rare postoperative complication. We present a case of a craniopharyngioma that ectopically recurred along the tract of a previous surgical route. CLINICAL PRESENTATION: A 73-year-old female patient presented 8 years earlier with a suprasellar craniopharyngioma. She underwent a right frontal craniotomy, with an interhemispheric transcallosal approach, for total microsurgical resection of the tumor. No postoperative radiotherapy was administered. Four years after surgery, magnetic resonance imaging studies revealed a well-circumscribed, heterogeneously enhancing, parasagittal mass with significant vasogenic edema in the right frontal lobe. Enlargement of the lesion was noted in subsequent radiological evaluations until 8 years after surgery, when the patient experienced a significant decline in neurocognitive status and the mass was surgically resected. INTERVENTION: Gross total resection of a histologically confirmed craniopharyngioma was achieved. CONCLUSION: To our knowledge, only eight previous case reports described the ectopic recurrence of a craniopharyngioma. Transplantation of tumor cells along the tract of a previous surgical route in six cases and dissemination in cerebrospinal fluid in two cases are presumed to be the primary mechanisms by which these ectopic recurrences occurred. The results of our literature review led us to conclude that total surgical resection, combined with careful inspection and irrigation of the surgical field, is the optimal treatment for preventing ectopic recurrences. Furthermore, it is recommended that, after primary craniopharyngioma resection, patients undergo long-term clinical and radiological follow-up monitoring for the rare development of an ectopically recurring tumor.

Aged↗
PubMed2005

A morphological study of ectopic plantar nail.

Ectopic nails are rare. Four adult patients presented to us, affected by true ectopic nails of the foot, sole, and toes, occurring bilaterally in one case. Full documentation of these anomalies was collected. The aim of this study was to better describe the morphologic features of ectopic plantar nails by using, besides histologic evaluation, transmission and scanning electron microscopy. New morphologic criteria were identified to determine if ectopic plantar nail differed from normal and ectopic hand nails. Morphologically, ectopic plantar nails are smaller than normal ones, but still form cuticles, nail grooves and nail folds, and periungual wrinkles. Furthermore, they form with a flat angle between the nail matrix and proximal nail fold, and have a nail plate interrupted by several transverse nails grooves.

Adult↗
PubMed1990

Horizontal Interactions in Cat Striate Cortex: III. Ectopic Receptive Fields and Transient Exuberance of Tangential Interactions.

In this study the developmental changes of intracortical connectivity are related to changes of cortical receptor fields (RFs). The RFs of striate cortex neurons of 4- to 8.5-week-old kittens, reared under normal conditions (NR) or in a selective visual environment (SE), were analysed quantitatively and compared with adult cats. To unmask weak inputs from outside the conventional RF (CRF), cell excitability was raised by iontophoretic application of glutamate (GLU) and/or bicuculline methiodide (BIC) or by light stimulation of the CRF. Both the dominant discharge region (DDR) and the total RF (TRF) area were significantly larger in NR and SE kittens than in adult cats. Moreover, in kittens 18% of the cells had additional ectopic fields that were excitatory, had similar orientation preferences as the CRF, and ranged 4 degrees to 23 degrees from the centre of the CRF. In 74% of the cases the ectopic fields were direction-selective and 70% of them preferred stimuli moving toward the CRF. Ectopic fields occurred mainly in supragranular cells, were similarly frequent in simple and complex cells and slightly more frequent in SE (20.7%) than in NR (13.3%) kittens. In adult cats only one of 83 cells tested had an ectopic field. It is concluded that the age-dependent decrease in the RF size, the laminar distribution of cells having an ectopic RF, and the numerical reduction of these cells with age correlate well with the organization and postnatal pruning of tangential projections, suggesting that these contribute to the elaboration of specific response properties. Moreover, the authors infer from the early presence and from the selectivity of ectopic fields that the system of horizontal intrinsic connections mediates far-reaching, excitatory interactions between cortical neurons with similar functional properties and serves as a substrate for the processing of global aspects of visual patterns.

Journal Article↗
PubMed1999

Radiofrequency catheter ablation of symptomatic ventricular ectopic beats originating in the right outflow tract.

Ectopic activity originating in the right ventricular outflow tract is a frequent finding and may result in severe symptoms such as dyspnea, palpitations, and lack of physical capacity correlated with a low cardiac output. In 12 consecutive symptomatic and drug refractory patients, we performed a study with intracardiac mapping and ablation procedure. The origin of the ectopic beats was identified, and the ablation procedure was performed. Patients were examined by serial ECG, Holter ECG, bicycle ECG, echocardiography, and thoracic X ray. At baseline, the mean number of ectopic beats was 23,823 during Holter ECG. No other arrhythmias were present. Patients underwent basic electro-physiological study, mapping process, and ablation in a single procedure. Ablation was performed with a deflectable thermocoupled catheter with tip electrodes of 4 mm. Criteria for identification of the origin of the ectopic beats included pace mapping with 12 leads and earliest endocardial activation. One male patient suffered from myocarditis; the other 11 patients had no underlying structural heart disease. The mean age was 38 years. Ablation procedure with delivered temperature of 70 degrees C was successful in 11 of 12 patients eliminating the focus. The mean procedural time was 79 +/- 34 minutes; mean fluoroscopy time was 13.8 +/- 8.8 minutes; and mean number of applications was 4.4 +/- 2.8. No adverse effects occurred during a follow-up period of 10 months after ablation. The mean number of ectopic beats per 24 hours after ablation was 317 +/- 599 with a P value of 0.00024. The clinical symptoms improved in all but one patient. One patient had a recurrence after 2 months that could be successfully treated by a second procedure. In our experience, temperature guided radiofrequency catheter ablation is safe and effective for the treatment of patients with symptomatic ectopic activity of the right outflow tract. As long as we lack the experience of a greater patient cohort and a longer follow-up, only drug resistant and highly symptomatic patients should be selected.

Adult↗
PubMed1999

Radiofrequency catheter ablation of frequent monomorphic ventricular ectopic activity.

INTRODUCTION: Frequent ventricular ectopic beats can result in severe symptoms and may even be incapacitating in some patients. Although radiofrequency catheter ablation is an effective and safe therapy for drug refractory idiopathic ventricular tachycardia, it has not been widely used in ventricular ectopy. The purpose of this study was: (1) to assess the potential role of catheter ablation in eliminating monomorphic ventricular ectopy in symptomatic patients regarding feasibility and safety and (2) to determine the usefulness of various mapping strategies. METHODS AND RESULTS: Forty-one patients with symptomatic ventricular ectopic activity (right ventricular origin in 23 patients, left ventricular origin in 18 patients) were enrolled. The mean frequency of ventricular ectopic beats was 1512+/-583/hour documented by Holter ECG monitoring. These patients had previously been unable to tolerate or had been unsuccessfully treated with a mean of 3+/-1 antiarrhythmic agents. The site of origin was mapped using earliest endocardial activation times, unipolar electrograms and pace mapping. Radiofrequency ablation was successful in 34 (83 %) of 41 patients. Multivariate logistic regression analysis revealed pace mapping as the only independent predictor for a successful ablation site (P < 0.01). After a follow-up of 3 months, the overall success rate was 71%. The mean frequency of ventricular ectopic beats after successful ablation was 12+/-10 ventricular premature beat/hour. CONCLUSION: Radiofrequency catheter ablation is an effective and safe treatment for frequent symptomatic drug refractory monomorphic ventricular ectopic activity. Pace mapping predicts best successful ablation of ventricular ectopic beats.

Adolescent↗
PubMed1985

Differential expression of the human gonadotropin alpha gene in ectopic and eutopic cells.

We have analyzed the regulation of the alpha gonadotropin gene in eutopic placental cells and ectopic tumor cells by constructing a series of plasmid vectors containing alpha genomic 5' flanking DNA placed upstream of the gene encoding the bacterial enzyme chloramphenicol acetyltransferase (CAT). These plasmid DNAs were transfected into a eutopic (JAr) and an ectopic (HeLa) cell line. Both cell types expressed the CAT gene from plasmid constructs containing as much as 1,500 base pairs (bp) and as little as 140 bp of alpha 5' flanking DNA; JAr cells were considerably more efficient than HeLa cells. Ectopic and eutopic cells differed qualitatively in their expression from these alpha-CAT constructs when cells were treated with cAMP or butyrate. Butyrate induced alpha expression in HeLa cells but not in JAr cells, while cAMP induced expression in JAr cells. These results are consistent with and extend previous observations suggesting that there are cell-specific differences in the regulation of alpha gene expression in ectopic and eutopic cells. However, by using deletion constructs of the alpha-CAT gene, we found that the basal expression and cell-specific induction of the alpha gene in ectopic and eutopic cells were dependent on the same 140 bp of alpha 5' flanking DNA. These 140 bp were sequenced and found to contain a 9-bp stretch of DNA homologous with the consensus viral enhancer sequence. Such features of alpha expression common to both ectopic and eutopic cells may be involved in the coordinate expression of the alpha gene and the tumorigenic phenotype observed in each cell type.

Acetyltransferases↗
PubMed1985

Ectopic intracranial retinoblastoma in childhood.

Twelve out of a series of 630 children with retinoblastoma, treated in the ocular oncology units at St Bartholomew's and Moorfields Eye Hospitals during the past 30 years, have developed ectopic intracranial retinoblastoma. The ectopic tumour occurred in the pineal region in eight children and in the suprasellar region in four. Ten patients had bilateral retinoblastoma, one unilateral disease, and one child presented with an isolated suprasellar tumour but no evidence of retinal disease. The interval from the initial diagnosis of retinoblastoma to the development of ectopic intracranial disease ranged from 4 to 70 months, median 34 months. Methods of treatment for the ectopic tumour varied, but all 12 children died with a median survival of only 8 months following the diagnosis of ectopic retinoblastoma. Subsequent spread of tumour to other sites within the central nervous system proved to be the most frequent cause of death. Ectopic intracranial retinoblastoma is a potentially curable neoplasm, but it requires adequate therapy to the whole neuraxis as well as high dose equivalent radiotherapy to the primary tumour.

Brain Neoplasms↗
PubMed2004

Indices of oxidative stress in eutopic and ectopic endometria of women with endometriosis.

This study was designed to determine the activities of superoxide dismutase and glutathione peroxidase and some of the lipid peroxidation indices (malondialdehyde and total sulfhydryl groups) in eutopic and ectopic endometria of patients with endometriosis. Ectopic endometrial tissues (ovarian cysts; n = 22) were obtained laparoscopically during the preovulatory period. Statistical analyses were made using the Wilcoxon signed-rank test. The levels of malondialdehyde and total sulfhydryl groups were similar in the eutopic and ectopic endometria, whereas the superoxide dismutase activity was found to be significantly higher in the latter (1,893 +/- 780 vs. 3,512 +/- 1,502 U/g protein; p = 0.002). Although the glutathione peroxidase activity was slightly lower in the ectopic than in the eutopic tissues, the difference was not found to be statistically significant. The malondialdehyde levels were positively correlated with the plasma 17beta-estradiol concentrations in the ectopic endometria (r = 0.683, p = 0.001). No such correlation was seen in the eutopic tissue. It is suggested that various factors, such as cytokines released by activated macrophages in the peritoneal fluid and 17beta-estradiol itself synthesized by the ovaries, may locally affect the oxidant status of ectopic endometria.

Adult↗
PubMed1997

Localization of T cells, interferon-gamma and HLA-DR in eutopic and ectopic human endometrium.

OBJECTIVES: Immunologic mechanisms are implicated in the pathogenesis of endometriosis and endometriosis-associated reproductive failure. The purpose of this study was to describe key immune response elements in eutopic and ectopic endometrium and to test the hypothesis that expression of CD3-positive T cells, the T-helper 1-type cytokine, IFN-gamma, and the antigen presentation marker, HLA-DR, vary throughout the menstrual cycle in eutopic endometrium and are more abundantly expressed in ectopic than in eutopic endometrium. METHODS: Eutopic and ectopic endometrium obtained at hysterectomy from 7 women with endometriosis were compared with hysterectomy specimens from 7 women with adenomyosis and 10 women without endometriosis or endometrial pathology. Tissues were formalin-fixed, paraffin-embedded, sectioned and stained using the biotin-streptavidin-alkaline phosphatase technique and antibodies to human CD3, IFN-gamma, and HLA-DR. Eutopic endometrial samples were histologically divided into menses (n = 5), proliferative (n = 9), and secretory (n = 10) phases. Positive control tissues (spleen) and negative controls (no primary antibody) were used in each experiment. RESULTS: T cells, IFN-gamma and HLA-DR-positive cells were observed in eutopic endometrial samples throughout the menstrual cycle. Glandular epithelium was CD3-negative except for CD3-positive cells surrounding and occasionally interdigitating between glandular epithelium. Glandular epithelium was IFN-gamma-positive and HLA-DR-positive in all phases except the proliferative phase. Staining was more often observed in the basalis than in the functionalis layer, ranging from patchy staining to the entire gland. T cells, IFN-gamma, and HLA-DR-positive stromal cells were more abundant in secretory endometrium than in proliferative samples. CD3, IFN-gamma, and HLA-DR-positive cells were scattered throughout the myometrium and concentrated in vessels. Higher intensity staining was observed in ectopic than in eutopic endometrium, with CD3 and HLA-DR-positive cells forming aggregates around IFN-gamma and HLA-DR-positive glands. The intensity of IFN-gamma staining in ectopic endometrium was similar to the intensity of staining observed in menstrual and late secretory basalis samples from eutopic endometrium. CONCLUSIONS: The results of this observational study suggest that activated T cells, IFN-gamma and upregulation of antigen presentation may play a role in normal endometrial physiology. The increased number of T cells, expression of IFN-gamma, and enhanced antigen presentation in ectopic compared to eutopic endometrium support the concept that cellular immune activation is involved in endometriosis and its sequelae.

Adult↗
PubMed2000

Initiation of atrial fibrillation by ectopic beats originating from the superior vena cava: electrophysiological characteristics and results of radiofrequency ablation.

BACKGROUND: The superior vena cava (SVC) has cardiac musculature extending from the right atrium. However, no previous study in humans has given details regarding the ectopic foci that initiate paroxysmal atrial fibrillation (PAF), which may originate from the SVC. METHODS AND RESULTS: A total of 130 patients with frequent attacks of PAF initiated by ectopic beats were included. Eight patients (6%) had spontaneous AF initiated by a burst of rapid ectopic beats from the SVC (located 19+/-7 mm above the junction of the SVC and right atrium), which was confirmed by multiplane angiographic and intracardiac echocardiographic visualization and was marked by a sharp SVC potential preceding atrial activity. During initial repetitive discharges, the group with SVC ectopy had a higher incidence of intravenous conduction block than the group with pulmonary vein ectopy (75% versus 37%; P=0.03). The activation time of the earliest intracardiac ectopic activities relative to ectopic P wave onset was significantly shorter in the SVC ectopy than the pulmonary vein ectopy group (37+/-15 versus 84+/-32 ms; P<0. 001). After 5+/-3 applications of radiofrequency energy, AF was eliminated. SVC angiography after ablation revealed a local indentation of the venous wall in one patient. Two patients manifested coexisting sinus rhythm and a "focal" fibrillating activity confined inside the SVC after radiofrequency ablation. During a follow-up period of 9+/-3 months, all 8 patients were free of antiarrhythmic drugs, without tachycardia recurrence or symptoms of SVC obstruction. CONCLUSIONS: Ectopic beats initiating PAF can originate from the SVC. A radiofrequency current delivered to eliminate these ectopies is a highly effective and safe way to prevent PAF.

Adult↗
PubMed1975

Anaylsis of ventricular activation and repolarization from intramural and epicardial potential distributions for ectopic beats in the intact dog.

Ventricular activation and repolarization were examined by measuring intramural and epicardial potential distributions during ectopic sequences in intact dogs. Potential distributions were used because they provided a direct measure of all of repolarization. Ectopic sequences produced almost unidirectional excitation across the heart along with repolarization events that were different from normal. During ectopic repolarization, positive potentials occurred over a broad area surrounding the ectopic focus, and negative potentials occurred over a large area on the opposite side of the heart where excitation terminated. The potentials in the walls of both ventricles were more positive in the outer layers and more negative in the inner layers, a gradient similar to normal. A maximum initially was at the ectopic site with a magnitude greater than that of the minimum, but the maximum subsequently decreased in magnitude and shifted toward the minimum while the minimum increased in magnitude. The steepest gradients were initially around the maximum, and they then shifted toward the minimum. The results show that ventricular repolatization potential distributions during ectopic beats are predominantly influenced by gradients from one side of the heart to the other (transventricular gradients) in contrast to normal repolatization distributions which are predominantly influenced by gradients across the wall (transmural gradients).

Animals↗
PubMed2003

Ectopic pregnancy rates with day 3 versus day 5 embryo transfer: a retrospective analysis.

BACKGROUND: Blastocyst transfer may theoretically decrease the incidence of ectopic pregnancy following IVF-ET in view of the decreased uterine contractility reported on day 5. The purpose of our study is to specifically compare the tubal pregnancy rates between day 3 and day 5 transfers. METHODS: A retrospective analysis of all clinical pregnancies conceived in our IVF program since 1998 was performed. The ectopic pregnancy rates were compared for day 3 and day 5 transfers. RESULTS: There were 623 clinical pregnancies resulting from day 3 transfers of which 22 were ectopic (3.5%). In day 5 transfers, there were 13 ectopic pregnancies out of 333 clinical pregnancies (3.9%). The difference between these rates is not statistically significant (P = 0.8). CONCLUSIONS: Our data suggests that the ectopic pregnancy rate is not reduced following blastocyst transfer compared to day 3 transfer. While there may be several benefits to extended culture in IVF, the decision to offer blastocyst transfer should be made independently from the issue of ectopic pregnancy risk.

Journal Article↗
PubMed2006

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery.

BACKGROUND: ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. CASE PRESENTATION: A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. CONCLUSION: This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe.

Adrenocorticotropic Hormone↗
PubMed1994

Ectopic Hoxa-1 induces rhombomere transformation in mouse hindbrain.

Homeobox genes are expressed with a specific spatial and temporal order, which is essential for pattern formation during the early development of both invertebrates and vertebrates. Here we show that widespread ectopic expression of the Hoxa-1 (Hox 1.6) gene directed by a human beta-actin promoter in transgenic mice is embryolethal and produces abnormal phenotypes in a subset of domains primarily located in anterior regions. Interestingly, this abnormal development in the Hoxa-1 transgenic mice is associated with ectopic expression of the Hoxb-1 (Hox 2.9) gene in select hindbrain regions. At gestation day 9.5, two domains of strong Hoxb-1 expression are found in the anterior region of the hindbrains of Hoxa-1 transgenic embryos. One region represents the normal pattern of Hoxb-1 expression in rhombomere 4 and its associated migrating neural crest cells, while another major domain of Hoxb-1 expression consistently appears in rhombomere 2. Similar ectopic domains of beta-galactosidase activity are detected in dual transgenic embryos containing both beta-actin/Hoxa-1 transgene and a Hoxb-1/lacZ reporter construct. Expression of another lacZ reporter gene that directs beta-galactosidase activity predominantly in rhombomere 2 is suppressed in the Hoxa-1 transgenic embryos. We have also detected weaker and variable ectopic Hoxb-1 expression in rhombomeres 1, 3 and 6. No ectopic Hoxb-1 expression is detected in rhombomere 5 and the expression of Hoxa-3 and Krox-20 in this region is unchanged in the Hoxa-1 transgenic embryos. While no obvious change in the morphology of the trigeminal or facial-acoustic ganglia is evident, phenotypic changes do occur in neurons that emanate from rhombomeres 2 and 3 in the Hoxa-1 transgenic embryos. Additionally, alterations in the pattern of Hoxa-2 and Hoxb-1 expression in a subpopulation of neural crest cells migrating from the rhombomere 2 region are detected in these transgenics. Taken together, these data suggest that ectopic Hoxa-1 expression can reorganize select regions of the developing hindbrain by inducing partial transformations of several rhombomeres into a rhombomere-4-like identity.

Actins↗
PubMed1998

Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling.

Patterning of the vertebrate limb along the anterior-posterior axis is controlled by the zone of polarizing activity (ZPA) located at the posterior limb margin. One of the vertebrate Hh family members, Shh, has been shown to be able to mediate the function of the ZPA. Several naturally occurring mouse mutations with the phenotype of preaxial polydactyly exhibit ectopic Shh expression at the anterior limb margin. In this study, we report the molecular characterization of a spontaneous mouse mutation, Doublefoot (Dbf). Dbf is a dominant mutation which maps to chromosome 1. Heterozygous and homozygous embryos display a severe polydactyly with 6 to 8 digits on each limb. We show here that Shh is expressed normally in Dbf mutants. In contrast, a second Hh family member, Indian hedgehog (Ihh) which maps close to Dbf, is ectopically expressed in the distal limb bud. Ectopic Ihh expression in the distal and anterior limb bud results in the ectopic activation of several genes associated with anterior-posterior and proximal-distal patterning (Fgf4, Hoxd13, Bmp2). In addition, specific components in the Hedgehog pathway are either ectopically activated (Ptc, Ptc-2, Gli1) or repressed (Gli2). We propose that misexpression of Ihh, and not a novel Smoothened ligand as recently suggested (Hayes et al., 1998), is responsible for the Dbf phenotype. We consider that Ihh has a similar activity to Shh when expressed in the early Shh-responsive limb bud. To determine whether Dbf maps to the Ihh locus, which is also on chromosome 1, we performed an interspecific backcross. These results demonstrate that Dbf and Ihh are genetically separated by approximately 1.3 centimorgans, suggesting that Dbf mutation may cause an exceptionally long-range disruption of Ihh regulation. Although this leads to ectopic activation of Ihh, normal expression of Ihh in the cartilaginous elements is retained.

Animals↗