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1.
Nat Rev Neurol ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152460

RESUMO

Hydrocephalus is the most common neurosurgical disorder worldwide and is characterized by enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles resulting from failed CSF homeostasis. Since the 1840s, physicians have observed inflammation in the brain and the CSF spaces in both posthaemorrhagic hydrocephalus (PHH) and postinfectious hydrocephalus (PIH). Reparative inflammation is an important protective response that eliminates foreign organisms, damaged cells and physical irritants; however, inappropriately triggered or sustained inflammation can respectively initiate or propagate disease. Recent data have begun to uncover the molecular mechanisms by which inflammation - driven by Toll-like receptor 4-regulated cytokines, immune cells and signalling pathways - contributes to the pathogenesis of hydrocephalus. We propose that therapeutic approaches that target inflammatory mediators in both PHH and PIH could address the multiple drivers of disease, including choroid plexus CSF hypersecretion, ependymal denudation, and damage and scarring of intraventricular and parenchymal (glia-lymphatic) CSF pathways. Here, we review the evidence for a prominent role of inflammation in the pathogenic mechanism of PHH and PIH and highlight promising targets for therapeutic intervention. Focusing research efforts on inflammation could shift our view of hydrocephalus from that of a lifelong neurosurgical disorder to that of a preventable neuroinflammatory condition.

2.
World Neurosurg ; 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32014543

RESUMO

BACKGROUND: Research experience is believed to be an important component of the neurosurgery residency application process. One measure of research productivity is publication volume. The preresidency publication volume of U.S. neurosurgery interns and any potential association between applicant publication volume and the match results of top-ranked residency programs have not been well characterized. OBJECTIVE: In this study, we sought to characterize the preresidency publication volume of U.S. neurosurgery residents in the 2018-2019 intern class using the Scopus database. METHODS: For each intern, we recorded the total number of publications, total number of first or last author publications, total number of neuroscience-related publications, mean number of citations per publication, and mean impact factor of the journal per publication. Preresidency publication volumes of interns at the top-25 programs (based on a composite ranking score according to 4 different ranking metrics) were compared with those at all other programs. RESULTS: We found that 82% of neurosurgery interns included in the analysis (190 interns from 95 programs) had at least 1 publication. The average number of publications per intern among all programs was 6 ± 0.63 (mean ± standard error of the mean). We also found that interns at top-25 neurosurgery residency programs tended to have a higher number of publications (8.3 ± 1.2 vs. 4.8 ± 0.7, P = 0.0137), number of neuroscience-related publications (6.8 ± 1.1 vs. 4.1 ± 0.7, P = 0.0419), and mean number of citations per publication (9.8 ± 1.7 vs. 5.7 ± 0.8, P = 0.0267) compared with interns at all other programs. CONCLUSIONS: Our results provide a general estimate of the preresidency publication volume of U.S. neurosurgery interns and suggest a potential association between publication volume and matching in the top-25 neurosurgery residency programs.

3.
Front Cell Neurosci ; 13: 515, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803025

RESUMO

Epilepsy is a common neurological disorder characterized by recurrent and unprovoked seizures thought to arise from impaired balance between neuronal excitation and inhibition. Our understanding of the neurophysiological mechanisms that render the brain epileptogenic remains incomplete, reflected by the lack of satisfactory treatments that can effectively prevent epileptic seizures without significant drug-related adverse effects. Type 2 K+-Cl- cotransporter (KCC2), encoded by SLC12A5, is important for chloride homeostasis and neuronal excitability. KCC2 dysfunction attenuates Cl- extrusion and impairs GABAergic inhibition, and can lead to neuronal hyperexcitability. Converging lines of evidence from human genetics have secured the link between KCC2 dysfunction and the development of epilepsy. Here, we review KCC2 mutations in human epilepsy and discuss potential therapeutic strategies based on the functional impact of these mutations. We suggest that a strategy of augmenting KCC2 activity by antagonizing its critical inhibitory phosphorylation sites may be a particularly efficacious method of facilitating Cl- extrusion and restoring GABA inhibition to treat medication-refractory epilepsy and other seizure disorders.

4.
J Neurosurg Pediatr ; : 1-10, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653819

RESUMO

Pediatric midline tumors are devastating high-grade lesions with a dismal prognosis and no curative surgical options. Here, the authors report the clinical presentation, surgical management, whole-exome sequencing (WES), and clonality analysis of a patient with a radically resected H3K27M-mutant pineal parenchymal tumor (PPT) and spine metastases consistent with PPT of intermediate differentiation (PPTID). They identified somatic mutations in H3F3A (H3K27M), FGFR1, and NF1 both in the original PPT and in the PPTID metastases. They also found 12q amplification containing CDK4/MDM2 and chromosome 17 loss of heterozygosity overlapping with NF1 that resulted in biallelic NF1 loss. They noted a hypermutated phenotype with increased C>T transitions within the PPTID metastases and 2p amplification overlapping with the MYCN locus. Clonality analysis detected three founder clones maintained during progression and metastasis. Tumor clones present within the PPTID metastases but not the pineal midline tumor harbored mutations in APC and TIMP2.While the majority of H3K27M mutations are found in pediatric midline gliomas, it is increasingly recognized that this mutation is present in a wider range of lesions with a varied morphological appearance. The present case appears to be the first description of H3K27M mutation in PPTID. Somatic mutations in H3F3A, FGFR1, and NF1 have been suggested to be driver mutations in pediatric midline gliomas. Their clonality and presence in over 80% of tumor cells in our patient's PPTID are consistent with similarly crucial roles in early tumorigenesis, with progression mediated by copy number variations and chromosomal aberrations involving known oncogenes and tumor suppressors. The roles of APC and TIMP2 mutations in progression and metastasis remain to be investigated.

5.
Front Cell Neurosci ; 13: 425, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616254

RESUMO

Background: ATP1A3 encodes the α3 subunit of the Na+/K+ ATPase, a fundamental ion-transporting enzyme. Primarily expressed in neurons, ATP1A3 is mutated in several autosomal dominant neurological diseases. To our knowledge, damaging recessive genotypes in ATP1A3 have never been associated with any human disease. Atp1a3 deficiency in zebrafish results in hydrocephalus; however, no known association exists between ATP1A3 and human congenital hydrocephalus (CH). Methods: We utilized whole-exome sequencing (WES), bioinformatics, and computational modeling to identify and characterize novel ATP1A3 mutations in a patient with CH. We performed immunohistochemical studies using mouse embryonic brain tissues to characterize Atp1a3 expression during brain development. Results: We identified two germline mutations in ATP1A3 (p. Arg19Cys and p.Arg463Cys), each of which was inherited from one of the patient's unaffected parents, in a single patient with severe obstructive CH due to aqueductal stenosis, along with open schizencephaly, type 1 Chiari malformation, and dysgenesis of the corpus callosum. Both mutations are predicted to be highly deleterious and impair protein stability. Immunohistochemical studies demonstrate robust Atp1a3 expression in neural stem cells (NSCs), differentiated neurons, and choroid plexus of the mouse embryonic brain. Conclusion: These data provide the first evidence of a recessive human phenotype associated with mutations in ATP1A3, and implicate impaired Na+/K+ ATPase function in the pathogenesis of CH.

6.
Transl Neurosci ; 10: 233-234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31497319

RESUMO

Timely dissemination of results from clinical studies is crucial for the advancement of knowledge and clinical decision making. A large body of research has shown that up to half of clinical trials do not publish their findings. In this study, we sought to determine whether clinical trial publication rates within neurology have increased over time. Focusing on neurology clinical trials completed between 2008 to 2014, we found that while the overall percentage of published trials has not changed (remaining at approximately 50%), time to publication has significantly decreased. Our findings suggest that clinical trials within neurology are being published in a more timely manner.

7.
Theranostics ; 9(17): 4959-4970, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410194

RESUMO

The strongest genetic risk factor for Alzheimer's disease (AD) is the Apolipoprotein E type 4 allele (ApoE ε4). The interaction between sex and ApoE ε4 carrier status on AD risk remains an area of intense investigation. We hypothesized that sex modulates the relationship between ApoE ε4 carrier status and brain tau deposition (a quantitative endophenotype in AD) in individuals with mild cognitive impairment (MCI). Methods: Preprocessed 18F-AV-1451 tau and 18F-AV-45 amyloid PET images, T1-weighted structural magnetic resonance imaging (MRI) scans, demographic information, and cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau) measurements from 108 MCI subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. After downloading pre-processed images from ADNI, an iterative reblurred Van Cittertiteration partial volume correction (PVC) method was applied to all PET images. MRIs were used for PET spatial normalization. Regions of interest (ROIs) were defined in standard space, and standardized uptake value ratio (SUVR) images relative to cerebellum were computed. ApoE ε4 by sex interaction analyses on 18F-AV-1451 and CSF tau (t-tau, p-tau) were assessed using generalized linear models. The association between 18F-AV-1451 SUVR and CSF tau (t-tau, p-tau) was assessed. Results: After applying PVC and controlling for age, education level and global cortical 18F-AV-45 SUVR, we found that the entorhinal cortex, amygdala, parahippocampal gyrus, posterior cingulate, and occipital ROIs exhibited a significant ApoE ε4 by sex interaction effect (false discovery rate P < 0.1) among MCI individuals. We also found a significant ApoE ε4 by sex interaction effect on CSF t-tau and p-tau. 18F-AV-1451 SUVR in the 5 ROIs with ApoE ε4 by sex interaction was significantly correlated with CSF p-tau and t-tau. Conclusions: Our findings suggest that women are more susceptible to ApoE ε4-associated accumulation of neurofibrillary tangles in MCI compared to males. Both CSF tau (p-tau, t-tau) and brain tau PET are robust quantitative biomarkers for studying ApoE ε4 by sex effects on brain tau deposition in MCI participants.

8.
Transl Neurosci ; 10: 195-199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31410303

RESUMO

Objective: To describe and assess the educational value of a functional neurosurgery clinical shadowing and research tutorial for pre-medical trainees. Design: Program participants observed functional neurosurgery procedures and conducted basic science and clinical research in neurosurgery fields. Former participants completed a brief online survey to evaluate their perspectives and experiences throughout the tutorial. Setting: Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Participants: 15 pre-medical and post-baccalaureate trainees participated in the tutorial. All former tutorial participants were emailed. Results: 11/15 former participants responded to the survey. Survey results suggest that the tutorial program increased participants' understanding of and interest in neurosurgery and related fields in neuroscience. Conclusions: The functional neurosurgery medical tutorial provides valuable clinical and research exposure in neurosurgery fields for pre-medical trainees. Our work is a preliminary step in addressing the crucial challenge of training the next generation of neurosurgeon-scientists by providing a pedagogical paradigm for development of formal experiences that integrate original scientific research with clinical neurosurgery exposure.

9.
Development ; 146(10)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31023879

RESUMO

Muscle precursors need to be correctly positioned during embryonic development for proper body movement. In zebrafish, a subset of hypaxial muscle precursors from the anterior somites undergo long-range migration, moving away from the trunk in three streams to form muscles in distal locations such as the fin. We mapped long-distance muscle precursor migrations with unprecedented resolution using live imaging. We identified conserved genes necessary for normal precursor motility (six1a, six1b, six4a, six4b and met). These genes are required for movement away from somites and later to partition two muscles within the fin bud. During normal development, the middle muscle precursor stream initially populates the fin bud, then the remainder of this stream contributes to the posterior hypaxial muscle. When we block fin bud development by impairing retinoic acid synthesis or Fgfr function, the entire stream contributes to the posterior hypaxial muscle indicating that muscle precursors are not committed to the fin during migration. Our findings demonstrate a conserved muscle precursor motility pathway, identify dynamic cell movements that generate posterior hypaxial and fin muscles, and demonstrate flexibility in muscle precursor fates.

10.
Trends Mol Med ; 25(6): 467-469, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30975633

RESUMO

Tripartite motif 71 (Trim71)/lineage defective 41 (lin-41) is the primary target of the ancient lethal 7 (let-7) miRNA that is essential for survival and development across animal phylogeny. Recent work identified Trim71 as a critical regulator of mammalian neural stem cell (NSC) fate and a bona fide human disease gene in congenital hydrocephalus (CH). Studying TRIM71 as a paradigm of NSC involvement in CH is a remarkable opportunity to better understand the mechanisms that regulate the timing of brain development and the pathogenesis of the most common pediatric neurosurgical disorder.

11.
J Clin Neurosci ; 62: 80-82, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30655234

RESUMO

We performed a retrospective study to characterize the timing and prevalence of revision and removal surgeries after spinal cord stimulator (SCS) implantation in patients with chronic pain. In our analysis of 100 patients who had SCS implants, we found that 34% of patients underwent revision surgery and 53% of patients had their implant removed. Of the patients who required revision surgeries, the majority (56%) eventually opted for removal of their SCS system. The median time to the first revision surgery was 16 months post implantation and the median time to removal was 39 months post implantation. Our findings demonstrate that most SCS systems are removed within a few years post implantation, highlighting the clinical need for a more complete understanding of SCS technology in order to refine patient selection criteria.


Assuntos
Reoperação/estatística & dados numéricos , Estimulação da Medula Espinal , Adulto , Idoso , Dor Crônica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Próteses e Implantes , Estudos Retrospectivos , Fatores de Tempo
12.
Front Neurosci ; 12: 652, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30297982

RESUMO

We conducted a knowledge, attitude, and practice (KAP) survey of fragile X-associated disorders (FXD) in Serbia in order to obtain baseline quantitative and qualitative KAP data on fragile X mental retardation 1 gene (FMR1) pre- and full mutations (PM, FM). The survey's 16-item questionnaire included a knowledge component (12/16), such as self-assessment knowledge (SAK) and factual knowledge (FK, 2/5 questions for PM, FXTAS and FXPOI). Education-directed attitudes in the FXD field and FMR1 DNA testing practices had 4/16 items, including brief case vignettes of FXTAS and FXPOI, respectively. The study's cohort consisted of primary care physicians (referred to as "physicians" in the rest of the text) throughout Serbia (n = 284, aged 26-64 years, 176/284, 62.2% in Belgrade, Serbia) and senior medical students (n = 245, aged 23-30 years; 33.5% males) at the Belgrade School of Medicine. Strikingly, half of the survey respondents indicated "not having any" knowledge for the fragile X gene premutation and FXD. Physicians were more likely to indicate "not having any" knowledge than students (41.2% of physicians vs. 13.1% of students, P < 0.05). Roughly half of the students had "minimal knowledge" (53.5 vs. 30.5% of physicians, P < 0.05). Low FK was common in the cohort, as few physicians had "all correct answers" (7.5 vs. 3.7% of students, P < 0.05; 16.5 vs. 9.5% of students for the 2/5 premutation-related questions). Statistical analyses identified physicians' practice setting and length of clinical experience as predictors of the lack of FK on questions related to FXD. Physicians were more likely than students to indicate "strongly agreed" to expand their knowledge of the gene premutation and FXD (90.9 vs. 66.7% of students, P < 0.01). However, students more frequently indicated that they are willing to recommend DNA testing in their future practices than physicians (93.5 vs. 64.8% of physicians, P < 0.001). In conclusion, there is a major gap in knowledge regarding fragile X gene PM and FXD among the study's participants in Serbia. The study's informative-educational survey serves as an initial step in the process of enhancing the KAP of medical professionals with regards to the fragile X gene premutation and FXD.

13.
Yale J Biol Med ; 91(3): 323-331, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30258319

RESUMO

Failed back surgery syndrome (FBBS) is characterized by chronic pain that persists following spine surgery. In this review, we discuss the use of spinal cord stimulation (SCS) for FBBS treatment and how the clinical use of SCS may be influenced by private manufacturers. While SCS therapy can be promising for the appropriate patient, there remain knowledge gaps in understanding the full potential of SCS technology for delivering optimal therapeutic benefit. We caution that the use of SCS without a complete understanding of the technology may create exploitative situations that private manufacturers can capitalize on while subjecting patients to potentially unnecessary health and financial burdens.


Assuntos
Síndrome Pós-Laminectomia/cirurgia , Síndrome Pós-Laminectomia/terapia , Humanos , Neurocirurgia , Estimulação da Medula Espinal
14.
J Biol Rhythms ; 32(6): 621-626, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29129126

RESUMO

Artificial light in modern society has led to the ubiquity of light exposure at night as individuals work night shifts and use light-emitting electronic devices before bedtime. These aberrant light conditions have detrimental consequences on cognitive and mental health, compelling the need to understand the mechanisms by which light affects brain functions. Although it was believed that aberrant light impairs health by first disrupting circadian rhythms and sleep, we showed that chronic exposure to a light cycle termed T7 (3.5 h of darkness, 3.5 h of light) caused mood and learning dysfunction in adult mice independent of sleep deprivation or circadian arrhythmicity, suggesting the direct effects of aberrant light on brain function. However, the mechanisms by which light directly causes mood and learning dysfunction remain poorly understood. In this study, we sought to determine whether exposure to the T7 cycle disrupts adult hippocampal neurogenesis, given that suppressed neurogenesis has been correlated with mood and learning dysfunction. After exposing adult mice to the T7 light cycle, we analyzed adult hippocampal neurogenesis by examining cellular proliferation and number of adult-born neurons. Contrary to our hypothesis that T7 would suppress neurogenesis, we found that adult mice exposed to 2 or 10 weeks of the T7 light cycle did not exhibit deficits in hippocampal neurogenesis. Our findings suggest that the direct effects of light on mood and learning do not depend on adult hippocampal neurogenesis.


Assuntos
Ritmo Circadiano , Hipocampo/fisiologia , Neurogênese , Fotoperíodo , Privação do Sono/fisiopatologia , Animais , Iluminação/efeitos adversos , Camundongos
15.
J Neurosci ; 37(48): 11559-11571, 2017 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-29061699

RESUMO

Motoneurons establish a critical link between the CNS and muscles. If motoneurons do not develop correctly, they cannot form the required connections, resulting in movement defects or paralysis. Compromised development can also lead to degeneration because the motoneuron is not set up to function properly. Little is known, however, regarding the mechanisms that control vertebrate motoneuron development, particularly the later stages of axon branch and dendrite formation. The motoneuron disease spinal muscular atrophy (SMA) is caused by low levels of the survival motor neuron (SMN) protein leading to defects in vertebrate motoneuron development and synapse formation. Here we show using zebrafish as a model system that SMN interacts with the RNA binding protein (RBP) HuD in motoneurons in vivo during formation of axonal branches and dendrites. To determine the function of HuD in motoneurons, we generated zebrafish HuD mutants and found that they exhibited decreased motor axon branches, dramatically fewer dendrites, and movement defects. These same phenotypes are present in animals expressing low levels of SMN, indicating that both proteins function in motoneuron development. HuD binds and transports mRNAs and one of its target mRNAs, Gap43, is involved in axonal outgrowth. We found that Gap43 was decreased in both HuD and SMN mutants. Importantly, transgenic expression of HuD in motoneurons of SMN mutants rescued the motoneuron defects, the movement defects, and Gap43 mRNA levels. These data support that the interaction between SMN and HuD is critical for motoneuron development and point to a role for RBPs in SMA.SIGNIFICANCE STATEMENT In zebrafish models of the motoneuron disease spinal muscular atrophy (SMA), motor axons fail to form the normal extent of axonal branches and dendrites leading to decreased motor function. SMA is caused by low levels of the survival motor neuron (SMN) protein. We show in motoneurons in vivo that SMN interacts with the RNA binding protein, HuD. Novel mutants reveal that HuD is also necessary for motor axonal branch and dendrite formation. Data also revealed that both SMN and HuD affect levels of an mRNA involved in axonal growth. Moreover, expressing HuD in SMN-deficient motoneurons can rescue the motoneuron development and motor defects caused by low levels of SMN. These data support that SMN:HuD complexes are essential for normal motoneuron development and indicate that mRNA handling is a critical component of SMA.


Assuntos
Proteína Semelhante a ELAV 4/genética , Proteína Semelhante a ELAV 4/metabolismo , Neurônios Motores/fisiologia , RNA Mensageiro/fisiologia , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Animais , Animais Geneticamente Modificados , Axônios/fisiologia , Dendritos/genética , Dendritos/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , Peixe-Zebra
16.
Transl Neurosci ; 8: 7-8, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28400977

RESUMO

Fragile X syndrome (FXS) is the leading genetic cause of autism spectrum disorder (ASD) and inherited intellectual disability (ID) worldwide. Preclinical successes in understanding the biology of FXS have led to numerous translational attempts in human clinical trials of therapeutics that target the excitatory/inhibitory neural signaling imbalances thought to underlie FXS. Despite the preclinical success story, the negative results of the human clinical trials have been deemed to be at least in part disappointing by the field. In this commentary, we contend that such negative studies results in clinical trials may actually propel the FXS field forward by serving as important lessons for designing and implementing improved future clinical trials such that can objectively assess the full range of responses to new therapeutics.

17.
Neuroscience ; 349: 118-127, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28238851

RESUMO

A seizure is a sustained increase in brain electrical activity that can result in loss of consciousness and injury. Understanding how the brain responds to seizures is important for development of new treatment strategies for epilepsy, a neurological condition characterized by recurrent and unprovoked seizures. Pharmacological induction of seizures in rodent models results in a myriad of cellular alterations, including inflammation, angiogenesis, and adult neurogenesis. The purpose of this study is to investigate the cellular responses to recurrent pentylenetetrazole seizures in the adult zebrafish brain. We subjected zebrafish to five once-daily pentylenetetrazole-induced seizures and characterized the cellular consequences of these seizures. In response to recurrent seizures, we found histologic evidence of vasodilatation, perivascular leukocyte egress and leukocyte proliferation suggesting seizure-induced acute CNS inflammation. We also found evidence of increased proliferation, neurogenesis, and reactive gliosis following pentylenetetrazole-induced seizures. Collectively, our results suggest that the cellular responses to seizures in the adult zebrafish brain are similar to those observed in mammalian brains.


Assuntos
Encéfalo/efeitos dos fármacos , Convulsivantes/farmacologia , Pentilenotetrazol/farmacologia , Convulsões/fisiopatologia , Animais , Comportamento Animal , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Convulsões/induzido quimicamente , Peixe-Zebra
20.
J Cell Biol ; 211(4): 807-14, 2015 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-26598617

RESUMO

Cell-cell recognition guides the assembly of the vertebrate brain during development. δ-Protocadherins comprise a family of neural adhesion molecules that are differentially expressed and have been implicated in a range of neurodevelopmental disorders. Here we show that the expression of δ-protocadherins partitions the zebrafish optic tectum into radial columns of neurons. Using in vivo two-photon imaging of bacterial artificial chromosome transgenic zebrafish, we show that pcdh19 is expressed in discrete columns of neurons, and that these columnar modules are derived from proliferative pcdh19(+) neuroepithelial precursors. Elimination of pcdh19 results in both a disruption of columnar organization and defects in visually guided behaviors. These results reveal a fundamental mechanism for organizing the developing nervous system: subdivision of the early neuroepithelium into precursors with distinct molecular identities guides the autonomous development of parallel neuronal units, organizing neural circuit formation and behavior.


Assuntos
Caderinas/fisiologia , Colículos Superiores/citologia , Proteínas de Peixe-Zebra/fisiologia , Animais , Sequência de Bases , Proliferação de Células , Técnicas de Inativação de Genes , Dados de Sequência Molecular , Neurônios/fisiologia , Colículos Superiores/metabolismo , Peixe-Zebra
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