Biology subjects

Core, N.

Publications and source records attributed to Core, N..

3 recordsLinked to original sources

bioRxiv2025

Integrated 3D Light-Sheet and 2D Multiplex Imaging for Deep Histological Profiling of a Somatic Mouse Glioblastoma Model

Glioblastoma is a devastating brain cancer. Despite intense research, patient survival has not significantly increased over the past decades and efficient treatment is currently not available. Therefore, the fundamental understanding of the disease, based on the development of relevant animal models, combined with the development of efficient tools for their deep analysis, represents a priority. Neural Stem cells in the subventricular zone of the forebrain have been identified as cells of origin for glioblastoma, leading to the development of new somatic lineage models based on in vivo brain electroporation. While such models have been characterized in depths by sequencing approaches, systematic histological analyses are currently scarce. Here we present the multimodal histological characterization of a transgenesis independent somatic glioblastoma model in mice. Using 3D light sheet imaging we demonstrate that the model is highly reproducible, allowing quantitative evaluation of tumor growth over large cohorts. Using multiplex imaging by MICS technology we systematically characterize the cellular landscape and molecular composition of the induced tumors, as well as their micro- and macro-environments, and provide a resource of mouse compatible antibodies for cancer research. Finally, we use the model to show that tissue clearing and 3D light sheet microscopy of whole brains can be combined with subsequent multiplex imaging, allowing deep spatial characterization of the tumor proteome in pre-identified brain regions.

cancer biology↗

bioRxiv2020

Regulatory interactions between Vax1, Pax6, and miR-7 regionalize the lateral Ventricular-Subventricular Zone during post-natal Olfactory Bulb neurogenesis in mice

Several subtypes of interneurons destined for the olfactory bulb are continuously generated after birth by neural stem cells located in the ventricular-subventricular zones of the lateral ventricles. Future neuronal identity depends on the positioning of pre-determined neural stem cells along the ventricle walls, which, in turn, depends on delimited expression domains of transcription factors and their cross regulatory interactions. However, mechanisms underlying positional identity of neural stem cells are still poorly understood. Here we show that the transcription factor Vax1 controls the production of two specific neuronal sub-types. First, it is directly necessary to generate Calbindin expressing interneurons from ventro-lateral progenitors. Second, it represses the generation of dopaminergic neurons by dorso-lateral progenitors through inhibiting Pax6 expression in the dorso-lateral wall. We provide evidence that this repression occurs via activation of microRNA miR-7, targeting Pax6 mRNA.

neuroscience↗

bioRxiv2018

Neuronal integration in the adult olfactory bulb is a non-selective addition process

Adult neurogenesis is considered a competition in which neurons scramble during a critical period for integration and survival. Moreover, newborn neurons are thought to replace preexisting ones that die. Despite a wealth of evidence supporting this model, systematic in vivo observations of the process are still scarce. We used 2-photon imaging to study neuronal integration and survival directly in the olfactory bulb (OB) of living mice. Long-term tracking of over 1400 neurons demonstrated that cell-loss in the OB is virtually absent. Neuronal death resembling a critical period was induced by standard doses of BrdU or EdU, but disappeared when low doses of EdU were used, demonstrating toxicity. Finally, we demonstrate that the OB grows throughout life. This shows that neuronal selection during OB-neurogenesis does not occur during integration and argues against the existence of a critical period. Moreover, the OB is not a \"turnover\" system but shows lifelong neuronal addition.

neuroscience↗