Zebrafish as an Orthotopic Tumor Model for Retinoblastoma Mimicking Routes of Human Metastasis.

BACKGROUND: Retinoblastoma (RB) is the most common eye cancer in children that has a high mortality rate when left untreated. Mouse models for retinoblastoma have been established but are time- and cost-intensive. The aim of this work was to evaluate an orthotopic transplantation model of retinoblastoma in zebrafish that also allows for tracking migratory routes and to explore advantages and disadvantages with respect to drug testing. METHODS: Three fluorescence-labeled retinoblastoma cell lines (RB355, WERI-RB-1, Y79) were injected into the left eye of two-day-old zebrafish, while the un-injected right eye served as control. The migratory trajectories of injected retinoblastoma cells were observed until 8 days post injection (dpi), both in lateral and dorsal view, and measuring fluorescence intensity of injected cells was done for RB355 cells. RESULTS: Time until the onset of migration and routes for all three retinoblastoma cell lines were comparable and resulted in migration into the brain and ventricles of the forebrain, midbrain and hindbrain. Involvement of the optic nerve was observed in 10% of injections with the RB355 cell line, 15% with Y79 cells and 5% with WERI-RB-1 cells. Fluorescence intensity of injected RB355 cells showed an initial increase until five dpi, but then decreased with high variability until the end of observation. CONCLUSION: The zebrafish eye is well suited for the analysis of migratory routes in retinoblastoma and closely mirrors patterns of retinoblastoma metastases in humans.

H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion.

Increase in the size of human neocortex­acquired in evolution­accounts for the unique cognitive capacity of humans. This expansion reflects the evolutionarily enhanced proliferative ability of basal progenitors (BPs), including the basal radial glia and basal intermediate progenitors (bIPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, how the epigenome in BPs differs across species is not known. Here, we report that histone H3 acetylation is a key epigenetic regulation in bIP amplification and cortical expansion. Through epigenetic profiling of sorted bIPs, we show that histone H3 lysine 9 acetylation (H3K9ac) is low in murine bIPs and high in human bIPs. Elevated H3K9ac preferentially increases bIP proliferation, increasing the size and folding of the normally smooth mouse neocortex. H3K9ac drives bIP amplification by increasing expression of the evolutionarily regulated gene, Trnp1, in developing cortex. Our findings demonstrate a previously unknown mechanism that controls cortical architecture.

The Hinrichsen Embryology Collection: Digitization of Historical Histological Human Embryonic Slides and MRI of Whole Fetuses.

The number of human embryology collections is very limited worldwide. Some of these comprise the Carnegie Collection, Kyoto Collection, and the Blechschmidt Collection. One further embryonic collection is the Hinrichsen Collection of the Ruhr University Bochum, Germany, which also contains very well-preserved embryos/fetuses, along with approximately 16,000 histological sections. The digitization of this collection is indispensable to enable conservation of the collection for the future and to provide a large group of embryologists, researchers, and physicians access to these histological slides. A small selection of these scans is available at the website of the Digital Embryology Consortium [https://-human-embryology.org/wiki/Main_Page].

Developmental myosin heavy chain mRNA in masseter after orthognathic surgery: a preliminary study.

INTRODUCTION: A microarray study showed an increase of developmental myosin heavy chain (MyHC) mRNA in the masseter muscle after surgery. The aim of the study was to determine the expression of the embryonic MYH3 and perinatal MYH8 for use as potential marker for muscle adaptation after orthognathic surgery. MATERIAL AND METHODS: 24 adult patients with a prognathic (11) or retrognathic (13) mandible were involved in the study. 192 biopsies were taken from two parts of the muscles presurgically and 6 months following. The expression of MYH3 and MYH8 were quantified using real-time polymerase chain reaction (RT-PCR). Absolute quantification was done by CT-values. RESULTS: MYH3 was up-regulated in prognathia (8.5, P<0.001) and in retrognathia (2.8, P<0.043). MYH8 was up-regulated in retrognathia only (4.0, P<0.063) and down-regulated in prognathia (-1.6). MYH3 values correlated in retrognathic patients (P<0.005) before and after surgery. CONCLUSION: MYH3 and MYH8 could play a role in functional adaptation after orthognathic surgery and orofacial orthopaedics.

MGF- and myostatin-mRNA regulation in masseter muscle after orthognathic surgery.

Patients with prognathism and retrognathism show extensive morphologic changes after orthognathic surgery. The inability of muscles to adapt adequately might be one reason for observed relapses. The aim of this prospective study was to analyze the regulation of functional genes after surgery and changes in myosin heavy chain (MyHC) isoform expression, a potential molecular marker profile for inadequate muscle adaptation. 29 adult patients with prognathic and retrognathic mandibles were involved. A total of 232 muscle biopsies were taken from both masseter muscles presurgically and 6 months later. The mRNA expression of "mechano growth factor" (MGF), myostatin, and 3 MyHC isoforms were quantified by real-time polymerase chain reaction. The MGF mRNA was significantly up-regulated (P < .005), whereas myostatin mRNA showed no significant regulation. There was a shift in MyHC isoform expression. The MyHC-I mRNA was decreased (P < .005), whereas MyHC-IIa mRNA was increased (P < .005). The coherence of increased MGF expression and MyHC isoform shift 6 months after orthognatic surgery indicates an adequate muscle adaptation and higher mastication activity.