Midbrain GABAergic neurons control several aspects of behavior, but regulation their development and diversity is poorly understood. Here, we further refine the midbrain regions active in neurogenesis show correlation with expression transcription factor Gata2. Using tissue-specific inactivation ectopic expression, that Gata2 regulates neuron mouse midbrain, not rhombomere 1, where it needed serotonergic lineage. Without Gata2, all precursors embryonic fail to activate neuron-specific gene...

Local inhibitory GABAergic and excitatory glutamatergic neurons are important for midbrain dopaminergic hindbrain serotonergic pathways controlling motivation, mood, voluntary movements. Such reside both within the nuclei, in adjacent brain structures, including rostromedial laterodorsal tegmental nuclei. Compared to monoaminergic neurons, development, heterogeneity, molecular characteristics of these regulatory poorly understood. We show here that different subgroups associated with nuclei...

Oncofetal fibronectin (FN-EDB) and tenascin-C C domain (TNC-C) are nearly absent in extracellular matrix of normal adult tissues but upregulated malignant tissues. Both FN-EDB TNC-C developed as targets antibody-based therapies. Here we used peptide phage biopanning to identify a novel targeting (PL1, sequence: PPRRGLIKLKTS) that interacts with both TNC-C. Systemic PL1-functionalized model nanoscale payloads [iron oxide nanoworms (NWs) metallic silver nanoparticles] homed glioblastoma (GBM)...

Abstract In vivo phage display is widely used for identification of organ- or disease-specific homing peptides. However, the current in biopanning approaches fail to assess biodistribution specific peptide phages across tissues during screen, thus necessitating laborious and time-consuming post-screening validation studies on individual phages. Here, we adopted bioinformatics tools RNA sequencing analysis high-throughput (HTS) data estimate representation peptides vivo. The from screen were...

Abstract Glioblastoma is considered one of the most aggressive malignancies in adult and pediatric patients. Despite decades research no curative treatment available it thus remains associated with a very dismal prognosis. Although recent pre-clinical clinical studies have demonstrated feasibility chimeric antigen receptors (CAR) T cell immunotherapeutic approach glioblastoma, tumor heterogeneity loss remain among important challenges to be addressed. In this study, we identify...

Abstract Gata2 has essential roles in the development of many organs. During mouse inner ear morphogenesis, it is expressed otic vesicle and surrounding periotic mesenchyme from early on, but no defects null mice have been observed before lethality at embryonic day (E) 10.5. Here, we used conditional gene targeting to reveal role later stages development. We show that critically required E14.5–E15.5 onward for vestibular morphogenesis. Without semicircular ducts fail grow their normal size...

Inner ear develops from an induced surface ectoderm placode that invaginates and closes to form the otic vesicle, which then undergoes a complex morphogenetic process membranous labyrinth. morphogenesis is severely affected in Gata3 deficient mouse embryos, but onset basis of phenotype has not been known. We show here deficiency leads severe unique abnormalities during invagination. The invagination problems are accompanied often by formation morphological boundary between dorsal ventral cup...

Serotonergic and glutamatergic neurons of the dorsal raphe regulate many brain functions are important for mental health. Their functional diversity is based on molecularly distinct subtypes; however, development this heterogeneity poorly understood. We show that ventral neuroepithelium mouse anterior hindbrain divided into specific subdomains giving rise to serotonergic as well other types glia. The newly born precursors segregated subpopulations expressing vesicular glutamate transporter 3...

Netrin 1 plays key roles in axon guidance and neuronal migration during central nervous system (CNS) development. Outside the CNS, has been shown to be involved epithelial morphogenesis of various organs. We have that is essential for inner ear semicircular duct formation, but involvement receptors this process remained unknown. include members Deleted colorectal cancer (Dcc), Unc5-homologue integrin families. Here we analysed expression these receptor genes development verified phenotypes...

Targeted therapies have increased the treatment options for triple-negative breast cancer patients. However, paucity of targetable biomarkers and tumor heterogeneity limited ability precision-guided interventions to live up their full potential. As affinity-targeting ligands, aptamers show high selectivity toward target molecules. Compared with antibodies, lower molecular weight, stability during transportation, reduced immunogenicity, tissue uptake. Recently, we reported discovery GreenB1...

Disease-specific changes in tumors and other diseased tissues are an important target of research because they provide clues about the pathophysiology disease as well uncover potentially useful markers for diagnosis treatment. Here, we report a new cyclic peptide, CESPLLSEC (CES), that specifically accumulated (homed) intracranial U87MG WT-GBM model glioblastoma (GBM) from intravenous (IV) injection, associated with vasculature. Affinity chromatography tumor extracts on insolubilized CES...

Choroidal neovascularization (CNV) is a common ocular pathology that may be associated in variety of eye diseases. Although intravitreal injection treatment anti-vascular endothelial growth factor (anti-VEGF) drugs shows significant clinical benefits CNV treatment, the limitations current therapy need to addressed. The aim our study was investigate potential utility three C-end Rule (CendR) peptides (RPARPAR, PL3, iRGD) for targeting and evaluate efficacy treating experimental mice. We...

Abstract The inner ear is a complex sensory organ with hearing and balance functions. Gata3 Gata2 are expressed in the ear, to gain more insight into their roles otic development, we made detailed expression analysis chicken embryos. At early stages, was highly overlapping. later became prominent vestibular cochlear nonsensory epithelia. In contrast , mainly developing epithelia, reflecting importance of this factor sensory–neural development ear. While patterns both were conserved between...

Report6 November 2017Open Access Transparent process A complex genomic locus drives mtDNA replicase POLG expression to its disease-related nervous system regions Joni Nikkanen Research Programs Unit, Molecular Neurology, University of Helsinki, Finland Search for more papers by this author Juan Cruz Landoni Diego Balboa Biomedicum Stem Cell Center, Maarja Haugas Department Biosciences, Juha Partanen Anders Paetau HUSLAB and Pathology, Helsinki Hospital, Pirjo Isohanni Pediatric Children's...

Ectothermal reptiles have internal pigmentation, which is not seen in endothermal birds and mammals. Here we show that the development of dorsal neural tube-derived melanoblasts turtle Trachemys scripta regulated by similar mechanisms as other amniotes, but significantly later development, during second phase trunk crest emigration. The coincided with a morphological change tube between stages mature G15 G16. delaminated gathered carapacial staging area above at G16, differentiated into...

Abstract To achieve precision and selectivity, anticancer compounds nanoparticles (NPs) can be targeted with affinity ligands that engage malignancy-associated molecules in the blood vessels. While tumor-penetrating C-end Rule (CendR) peptides hold promise for tumor delivery, C-terminally exposed CendR accumulate undesirably non-malignant tissues expressing neuropilin-1 (NRP-1), such as lungs. One example of promiscuous is PL3 (sequence: AGRGRLVR), a peptide engages NRP-1 through its...

Disease-specific changes in tumors and other diseased tissues are an important target of research because they provide clues on the pathophysiology disease as well uncovering potentially useful markers for diagnosis treatment. Here, we report a new cyclic peptide, CESPLLSEC (CES), that specifically accumulated (homed) intracranial U87MG WT-GBM model glioblastoma from intravenous (IV) injection, associating with vasculature. Affinity chromatography tumor extracts insolubilized CES peptide...

ABSTRACT In vivo phage display is widely used for identification of organ- or disease-specific homing peptides. However, the current in biopanning approaches fail to assess biodistribution specific peptide phages across tissues during screen, thus necessitating laborious and time-consuming post-screening validation studies on individual phages. Here, we adopted bioinformatics tools RNA sequencing analysis high throughput (HTS) data estimate representation peptides . The from screen were...

ABSTRACT Targeted therapies have increased the treatment options for triple-negative breast cancer patients. However, paucity of targetable biomarkers and tumour heterogeneity limited ability precision-guided interventions to live up their full potential. As affinity targeting ligands, aptamers show high selectivity towards target molecules. Compared antibodies, lower molecular weight, stability during transportation, reduced immunogenicity, tissue uptake. Recently, we reported discovery...