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PubMed1981

In situ transcription analysis of chromatin template activity of the S-chromosome of Drosophila following high molar NaCl treatment.

The chromatin template activity of the polytene chromosomes in larval salivary glands of Drosophila hydei has been assayed by in situ transcription, on the fixed chromatin using E. coli RNA polymerase holoenzyme and 3H-UTP as the monitoring substrate, both with optimal salt and high salt concentration (1 M NaCl). Results reveal an increase in the net transcription of all chromosomes in the high salt treatment series in comparison with the control. The X-chromosomes of the male larval gland also shows an increase in the labelling following the high salt treatment, but the increase is significantly less than that of the autosomes of the same nucleus. On the basis of these findings it has been suggested that the X-chromosomal hyperactivity of the male, as normally known to exist, might be guided by an inherent modulation of the structure of the X-chromatin.

Animals↗

PubMed2004

MicroRNAs guide asymmetric DNA modifications guiding asymmetric organs.

In plants and animals, microRNAs have been shown to regulate target genes by inhibiting translation or altering target mRNA stability. In this issue of Developmental Cell, Bao et al. extend the known mechanisms of action of microRNAs to RNA-directed DNA methylation, a mechanism previously associated only with siRNA-mediated gene silencing.

Arabidopsis↗

PubMed2001

Long-term benefit of genotypic-guided therapy and prevalence of multinucleoside resistance in an Italian group of antiretroviral multiexperienced patients.

Multiple nucleoside resistance involves specific genetic changes in the HIV-1 reverse transcriptase gene, such as Q151M mutation and an insertion of two serine aminoacids at RT codon 69. Among 432 patients failing antiretroviral therapy, five (1.15%) harboured viruses with Q151M mutation into the RT gene and no viruses were identified harbouring insertion at codon 69. Also we have studied the long-term benefit of HIV genotypic testing with the failure to reach a viral load below 50 copies/ml within 1 year of antiretroviral therapy using as the primary end-point. A group of 64 HIV-positive antiretroviral multiexperienced patients were examined, all of them failing the current ART. HIV-RNA changed -0.8 log at month 4 and +0.1 log and -0.5 log at months 8 and 12, respectively. The proportion of patients with viral load below 50 copies/ml was 19.3, 32.8, and 28.1% at months 4, 8, and 12, respectively. In multidrug-experienced patients, genotype-guided therapy is not in fact able to achieve complete viral suppression in more than 30% of patients after 1 year of ART. The development of more precise resistance tests and interpretations are needed for better control of HIV replication. Other metabolic/pharmacokinetics factors of poor drug adherence should also be assessed.

Acquired Immunodeficiency Syndrome↗

PubMed2026

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy↗

PubMed2004

Experimental RNomics: a global approach to identifying small nuclear RNAs and their targets in different model organisms.

Non-messenger RNAs (nmRNAs) play a wide and essential role in cellular functions. Computational identification of novel nmRNAs in genomes of model organisms is severely restricted owing to their lack of an open reading frame. Hence, we describe experimental approaches for their identification by generating cDNA libraries derived from nmRNAs for which we coined the term experimental RNomics. Two different procedures are introduced for cDNA library construction. First, we describe the construction of a general purpose cDNA library from sized RNA fractions. Second, we introduce a more specialized RNomics strategy employing this approach to generate a cDNA library from a specific abundant class of nmRNAs. This is illustrated using as a paradigm the two families of small nucleolar RNAs that guide modification of nucleotides in rRNAs or spliceosomal RNAs small nuclear RNAs (snRNAs) by short antisense elements complementary to the modification site. Following the identification of novel members from the class of small nuclear RNAs by experimental RNomics, we demonstrate how their target sequences in rRNAs or snRNAs can be identified.

Base Sequence↗

PubMed1986

Characterization of the intron in the phage T4 thymidylate synthase gene and evidence for its self-excision from the primary transcript.

The td gene contains a 735 bp open reading frame within its 1017 bp intron. A 12 nucleotide stretch may form a stable secondary structure with the putative Shine-Dalgarno sequence of the intron open reading frame and thus impair its translation. SP6 RNA polymerase transcripts of the td gene synthesized in vitro at 40 degrees C encompass a 2.7 kb primary transcript, a 1.7 kb mRNA, and a 1 kb intron RNA. The excised intron RNA consisted of linear and cyclized forms. RNAase H studies and resistance of the cyclized intron to linearization by HeLa cell debranching enzyme suggest it to be circular. Self-splicing of isolated td primary transcript occurred only marginally at 28 degrees C, but increased progressively to 50 degrees C, and required the presence of both Mg++ and a guanosine cofactor. An internal guide sequence is evident which may align the 5' splice site with the 3' end, presumably for precise exon ligation.

Base Sequence↗

PubMed2026

YIPFα1A expression is regulated by multilayered molecular mechanisms.

Yip domain family (YIPF) proteins are five-pass transmembrane proteins that localize primarily to the Golgi apparatus. These proteins assemble into higher-order complexes with each α-subunit pairing specifically with a β-subunit to form a dimer which then assemble into complexes with two to four dimers. Notably, β-subunit expression depends on the corresponding α-subunit partner, and conventional transient overexpression of α-subunits has been extremely inefficient, hindering deeper analysis of YIPF complexes. To identify the cause of poor exogenous expression, we examined YIPF gene features and found two properties correlated with low expression: (i) rare-codon enrichment in the CDS and (ii) extended 3' UTRs. Experimental analyses focusing on YIPFα1A revealed that rare-codon enrichment suppresses expression mainly at the mRNA level, consistent with translation-coupled mRNA decay, whereas inclusion of the native 3' UTR enhances expression by increasing mRNA abundance. Deletion mapping further showed that a proximal 3' UTR segment (51-150) is necessary and sufficient for mRNA stabilization, thereby elevating both mRNA and protein levels. Conversely, a distal 3' UTR fragment (1116-2230) increased mRNA but not protein levels, suggesting translational repression resulting in a reduced protein-to-mRNA ratio. Together, these findings explain the discrepancy between endogenous and exogenous YIPFα1A expression and propose a multilayered regulatory model in which rare codons decrease mRNA, the proximal 3' UTR stabilizes mRNA, and the distal 3' UTR reduces translation. Impact statement Our work advances YIPF biology and identifies post‑transcriptional mechanisms governing multi‑pass membrane proteins. We show rare‑codon and 3' UTR‑based control of trafficking proteins-an area largely unexplored-and introduce a new paradigm for membrane‑traffic regulation that will guide future studies of complex assembly, localization, and homeostasis.

3' Untranslated Regions↗

PubMed2026

Multiomics Integration Identifies a Molecular Subtype of Intrahepatic Cholangiocarcinoma With Enhanced Benefit From Adjuvant Therapy.

Intrahepatic cholangiocarcinoma (iCCA) is a molecularly heterogeneous liver cancer with a poor prognosis. Improved stratification is needed to guide postoperative therapy. In this study, we applied integrative multiomics analysis to classify iCCA and identify biomarkers predictive of adjuvant treatment benefit. Using publicly available datasets (including whole exome sequencing, RNA sequencing, proteomics, and phosphoproteomics from FU-iCCA cohort and a transcriptomic cohort GSE244807), we defined 3 robust molecular subtypes of iCCA. These subtypes exhibited distinct genomic alterations, pathway activation, and immune microenvironments, with significant differences in overall survival (OS). Through protein-protein interaction network analysis and consensus feature selection using 10 clustering algorithms, we prioritized 8 marker genes distinguishing the subtypes. A Cox proportional-hazards model constructed from these markers stratified patients into high- and low-risk groups. High-risk iCCA, characterized by elevated expression of markers such as CLDN18, MUC1, and MUC5AC, had significantly worse OS in the absence of adjuvant therapy. Notably, in an independent validation of 174 patients with iCCA who underwent resection (single-center cohort), high expression of any of these 3 markers were associated with markedly prolonged OS in patients who received adjuvant chemotherapy or chemoembolization, compared with those who did not. In contrast, marker-negative patients showed no clear benefit from adjuvant therapy. In conclusion, our multiomics approach identified a high-risk, mucin-enriched subtype of iCCA. CLDN18, MUC1, and MUC5AC emerge as candidate predictive biomarkers for adjuvant chemotherapy benefit in iCCA, warranting prospective validation to improve personalized postoperative management.

Humans↗

PubMed1996

Two structurally different RNA molecules are bound by the spliceosomal protein U1A using the same recognition strategy.

BACKGROUND: Human U1A protein binds to hairpin II of U1 small nuclear RNA (snRNA) and, together with other proteins, forms the U1 snRNP essential in pre-mRNA splicing. U1A protein also binds to the 3' untranslated region (3'UTR) of its own pre-mRNA, inhibiting polyadenylation of the 3'end and thereby downregulating its own expression. The 3'UTR folds into an evolutionarily conserved secondary structure with two internal loops; one loop contains the sequence AUUGCAC and the other its variant AUUGUAC. The sequence AUUGCAC is also found in hairpin II of U1 snRNA; hence, U1A protein recognizes the same heptanucleotide sequence in two different structural contexts. In order to better understand the control mechanism of the polyadenylation process, we have built a model of the U1A protein-3'UTR complex based on the crystal structure of the U1A protein-hairpin II RNA complex which we determined previously. RESULTS: In the crystal structure of the U1A protein-hairpin II RNA complex the AUUGCAC sequence fits tightly into a groove on the surface of U1A protein. The conservation of the heptanucleotide in the 3'UTR strongly suggests that U1A protein forms identical sequence-specific contacts with the heptanucleotide sequence when complexed with the 3'UTR. The crystal structure of the hairpin II complex and the twofold symmetry in the 3'UTR RNA provide sufficient information to restrict the conformation of the 3'UTR RNA and have enabled us to build a model of the 3'UTR complex. CONCLUSIONS: In the U1A-3'UTR complex, sequence-specific interactions are made entirely by the conserved heptanucleotide and the last base pair (C:G) of the stem. The structure is stabilized by protein-protein contacts and by electrostatic interactions between basic amino acids of the protein and the phosphate backbone of the RNA stem regions. The formation of a protein dimer necessary for the inhibition of poly(A) polymerase requires a conformational change of the C termini of the proteins upon RNA binding. This mechanism could prevent the inhibition of poly(A) polymerase by free U1A protein. The model is consistent with biochemical data, and the protein-protein interactions within the 3'UTR complex account for the cooperativity of U1A protein binding to the 3'UTR. The model also serves as an important structural guide for designing further experiments to understand the interaction between the U1A-3'UTR complex and poly(A) polymerase.

Base Sequence↗

PubMed1991

Modification of Trypanosoma brucei mitochondrial rRNA by posttranscriptional 3' polyuridine tail formation.

Trypanosoma brucei mitochondrial transcripts can be posttranscriptionally processed by uridine addition or deletion. With editing of mRNAs, uridine addition and deletion create precisely altered reading frames. The addition of nonencoded uridines to mitochondrial guide RNAs results in a less precise modification. Although uridines are specifically added to the 3' termini, their number varies, which results in heterogeneous oligo(U) tails on guide RNAs. In this paper, we show that the mitochondrial 9S and 12S rRNAs are also modified by uridine addition. These modifications appear to have aspects in common with both RNA editing and oligo(U) tail formation. Metabolic labeling studies with intact mitochondria and [alpha-32P]UTP, in the absence of transcription, demonstrated the posttranscriptional timing of the event. T1 RNase comparison analyses of cytidine 3',5'-[5'-32P]biphosphate 3'-end-labeled and [alpha-32P]UTP metabolically labeled rRNAs, along with direct RNA sequencing of the 3' termini, identified the site of uridine addition and revealed the creation of an oligo(U) tail for both rRNAs. 12S and 9S rRNAs hybrid selected from total cell RNA exhibited the same modification, demonstrating the presence of this processing in vivo. Moreover, only 3'-poly(U)-tailed 9S and 12S rRNAs were detected in total cellular and mitochondrial RNAs, which suggests that they are the most abundant and probable mature forms. The 12S and 9S rRNA oligo(U) tails differed significantly from each other, with the 12S having a heterogeneous tail of 2 to 17 uridines and the 9S having a tail of precisely 11 uridines. The mechanism of formation and the function of the rRNA poly(U) tails remain to be determined.

Animals↗

PubMed2005

An algorithmic framework for genome-wide modeling and analysis of translation networks.

The sequencing of genomes of several organisms and advances in high throughput technologies for transcriptome and proteome analysis has allowed detailed mechanistic studies of transcription and translation using mathematical frameworks that allow integration of both sequence-specific and kinetic properties of these fundamental cellular processes. To understand how perturbations in mRNA levels affect the synthesis of individual proteins within a large protein synthesis network, we consider here a genome-scale codon-wide model of the translation machinery with explicit description of the processes of initiation, elongation, and termination. The mechanistic codon-wide description of the translation process and the large number of mRNAs competing for resources, such as ribosomes, requires the use of novel efficient algorithmic approaches. We have developed such an efficient algorithmic framework for genome-scale models of protein synthesis. The mathematical and computational framework was applied to the analysis of the sensitivity of a translation network to perturbation in the rate constants and in the mRNA levels in the system. Our studies suggest that the highest specific protein synthesis rate (protein synthesis rate per mRNA molecule) is achieved when translation is elongation-limited. We find that the mRNA species with the highest number of actively translating ribosomes exerts maximum control on the synthesis of every protein, and the response of protein synthesis rates to mRNA expression variation is a function of the strength of initiation of translation at different mRNA species. Such quantitative understanding of the sensitivity of protein synthesis to the variation of mRNA expression can provide insights into cellular robustness mechanisms and guide the design of protein production systems.

Algorithms↗

PubMed2006

In vitro antiviral activity of SCH446211 (SCH6), a novel inhibitor of the hepatitis C virus NS3 serine protease.

BACKGROUND: Current hepatitis C virus (HCV) therapies may cure approximately 60% of infections. They are often contraindicated or poorly tolerated, underscoring the need for safer and more effective drugs. A novel, alpha-ketoamide-derived, substrate-based inhibitor of the HCV serine protease (SCH446211) was developed. Compared with earlier reported inhibitors of similar chemical class, it has a P1'-P2' extension which provides extended interaction with the protease active site. The aim of this study was to evaluate the in vitro antiviral activity of SCH446211. METHODS: Binding constant of SCH446211 to HCV NS3 protease was measured with the chromogenic substrate in vitro cleavage assay. Cell-based activity of SCH446211 was evaluated in replicon cells, which are Huh-7 hepatoma cells stably transfected with a subgenomic HCV RNA as reported previously. After 72 h of incubation with SCH446211, viral transcription and protein expression were measured by real-time RT-PCR (TaqMan), quantitative in situ hybridization, immunoblot and indirect immunofluorescence. RESULTS: The binding constant of SCH446211 to HCV NS3 protease was 3.8 +/- 0.4 nM. HCV replication and protein expression were inhibited by SCH446211 in replicon cells as consistently shown by four techniques. In particular, based on quantitative real-time RT-PCR measurements, the IC50 and IC90 of SCH446211 were estimated to be 40 +/- 20 and 100 +/- 20 nM (n = 17), respectively. Long-term culture of replicon cells with SCH446211 reduced replicon RNA to <0.1 copy per cell. SCH446211 did not show cellular toxicity at concentrations up to 50 microM. CONCLUSIONS: SCH446211 is a potent inhibitor of HCV protease in vitro. Its extended interaction with the HCV NS3 protease active site is associated with potent in vitro antiviral activity. This observation is potentially a useful guide for development of future potent inhibitors against HCV NS3 protease.

Antiviral Agents↗

PubMedDate not supplied

Association between HLA class II antigens and hepatitis C virus infection.

The aim was to confirm the influence of HLA Class II antigens on the progression of HCV infection and to assess the relationship between these antigens and histological damage, HCV viral load and HCV genotype. 143 patients were enrolled and divided into three groups. Group A included 34 anti-HCV positive, HCV-RNA negative patients with ALT persistently normal; group B included 39 patients with HCV-RNA positive and abnormal ALT level; group C included 70 normal subjects. Serological HCL typing was performed with lymphocytotoxicity test by Terasaky and McClelland, using lymphobeads HLC class II. The frequency of HLA DR11 (5) was significantly higher in the control group (52.9%) and in group A (64.7%), than in group B (28.2%). Allele HLA DR6 was demonstrated in a similar proportion (26%) among control group and group B, while HLA DR14 (6) was less frequent among controls (18% vs 1.4%). In group A the frequency of HLA DR14 (6) was 3% compared to group B, HLA DR17 (3) was prevalent (15.4%) in group B. Liver damage was associated with the detection of HLA DR14 (6) and HLD DR17 (3) antigens. Significantly lower levels of HCV-RNA were measured in subjects with HLA DR11 (5) than in these with either DR6 or DR17 (3). HLA class II antigens appear crucial for resolution or progression of HCV hepatitis. The punctual identification of these genetic factors may, therefore, prove to be useful in predicting disease evolution, in guiding the appropriate therapy for patients with poor prognosis, and in encouraging the development of now therapeutic strategies.

Adult↗

PubMed1988

Deletion of nonconserved helices near the 3' end of the rRNA intron of Tetrahymena thermophila alters self-splicing but not core catalytic activity.

The self-splicing rRNA intron of Tetrahymena thermophila contains two stem-loop structures (P9.1 and P9.2) near its 3' end that are not conserved among group I introns. As a step toward deriving the smallest active self-splicing RNA, 78 nucleotides encompassing P9.1 and P9.2 have been deleted. This deletion has no effect on the core catalytic activity of the intron, as judged by its ability to catalyze poly(C) polymerization and other related reactions. In contrast, reactions at the 3' splice site of the rRNA precursor--exon ligation and intermolecular exon ligation--take place with reduced efficiency, and exon ligation becomes rate-limiting for self-splicing. Moreover, intermolecular exon ligation with pentaribocytidylic acid is inaccurate, occurring primarily at a cryptic site in the 3' exon. A deletion of 79 nucleotides that disrupts P9, as well as removing P9.1 and P9.2, has more severe effects on both the first and second steps of splicing. P9, a conserved helix at the 5' edge of the deletion point, can form stable alternative structures in the deletion mutants. This aberrant folding may be responsible for the reduced activity and accuracy of reactions with mutant precursors. Analysis of the cryptic site suggests that choice of the 3' splice site may not only depend on sequence but also on proximity to P9. In the course of these studies, evidence has been obtained for an alternative 5' exon-binding site distinct from the normal site in the internal guide sequence.

Animals↗

PubMed2002

Advanced diagnostic methods in oral and maxillofacial pathology. Part II: immunohistochemical and immunofluorescent methods.

The practice of pathology is currently undergoing significant change, in large part due to advances in the analysis of DNA, RNA, and proteins in tissues. These advances have permitted improved biologic insights into many developmental, inflammatory, metabolic, infectious, and neoplastic diseases. Moreover, molecular analysis has also led to improvements in the accuracy of disease diagnosis and classification. It is likely that, in the future, these methods will increasingly enter into the day-to-day diagnosis and management of patients. The pathologist will continue to play a fundamental role in diagnosis and will likely be in a pivotal position to guide the implementation and interpretation of these tests as they move from the research laboratory into diagnostic pathology. The purpose of this 2-part series is to provide an overview of the principles and applications of current molecular biologic and immunologic tests. In Part I, the biologic fundamentals of DNA, RNA, and proteins and methods that are currently available or likely to become available to the pathologist in the next several years for their isolation and analysis in tissue biopsies were discussed. In Part II, advances in immunohistochemistry and immunofluorescence methods and their application to modern diagnostic pathology are reviewed.

Antigens, Neoplasm↗

PubMed2005

In vitro construction of effective M1GS ribozymes targeting HCMV UL54 RNA segments.

Seven sequence-specific ribozymes (M1GS RNAs) derived in vitro from the catalytic RNA subunit of Escherichia coli RNase P and targeting the mRNAs transcribed by the UL54 gene encoding the DNA polymerase of human cytomegalovirus were screened from 11 ribozymes that were designed based on four rules: (1) the NCCA-3' terminal must be unpaired with the substrate; (2) the guide sequence (GS) must be at least 12 nt in length; (3) the eighth nucleotide must be U, counting from the site -1; and (4) around the cleavage site, the sites -1/+1/+2 must be U/G/C or C/G/C. Further investigation of the factors affecting the cleavage effect and the optimal ratio for M1GS/substrate was carried out. It was determined that the optimal ratio for M1GS/substrate was 2:1 and too much M1GS led to substrate degrading. As indicated above, several M1GS that cleaved HCMV UL54 RNA segments in vitro were successfully designed and constructed. Our studies support the use of ribozyme M1GS as antisense molecules to silence HCMV mRNA in vitro, and using the selection procedure as a general approach for the engineering of RNase P ribozymes.

Cloning, Molecular↗

PubMed1993

RNA editing in kinetoplastid mitochondria.

RNA editing in the mitochondrion of kinetoplastid protozoa results in the posttranscriptional addition and deletion of uridine residues in mRNAs. Editing of mRNAs can lead to the formation of initiation codons for mitochondrial translation, the correction of frame-shifted genes at the RNA level, and in extensively edited mRNAs, the formation of complete reading frames. Kinetoplastid RNA editing requires that genetic information from two or more separately transcribed genes be brought together to form the mature, edited mRNA. The information necessary for the proper insertion or deletion of uridines in the mRNA is present in small mitochondrial transcripts termed guide RNAs (gRNAs). Editing of mRNAs appears to be associated with a high molecular weight complex, called the editosome, containing specific gRNAs, unedited mRNAs, and proteins. Editing is likely a two-step process involving first the breakage of a phosphodiester bond at the editing site and formation of a chimeric molecule with a gRNA covalently joined to the 5' end of the 3' portion of an mRNA. The chimera is resolved by the rejoining of the 5' end of the mRNA to the 3' portion of the mRNA with the addition or deletion of a uridine at the junction point. Two models are proposed for the biochemical mechanism of RNA editing. The first is an enzymatic cascade of cleavage and ligation while the other supports successive rounds of transesterification. The obvious functional necessity for editing in kinetoplastid mitochondria is the formation of translatable mRNAs. Far less clear is the evolutionary origin of editing and the role editing plays in regulating mitochondrial gene expression.

Animals↗

PubMed2006

Drosophila Eph receptor guides specific axon branches of mushroom body neurons.

The conserved Eph receptors and their Ephrin ligands regulate a number of developmental processes, including axon guidance. In contrast to the large vertebrate Eph/Ephrin family, Drosophila has a single Eph receptor and a single Ephrin ligand, both of which are expressed within the developing nervous system. Here, we show that Eph and Ephrin can act as a functional receptor-ligand pair in vivo. Surprisingly, and in contrast to previous results using RNA-interference techniques, embryos completely lacking Eph function show no obvious axon guidance defects. However, Eph/Ephrin signaling is required for proper development of the mushroom body. In wild type, mushroom body neurons bifurcate and extend distinct branches to different target areas. In Eph mutants, these neurons bifurcate normally, but in many cases the dorsal branch fails to project to its appropriate target area. Thus, Eph/Ephrin signaling acts to guide a subset of mushroom body branches to their correct synaptic targets.

Animals↗