Biology subjects

Baumgart, J.

Publications and source records attributed to Baumgart, J..

4 recordsLinked to original sources

bioRxiv2022

Less is more - loss of EGFL7 improves memory by upregulation of VEGF-D

Neural stem cells reside in a specialized neurogenic niche of the hippocampus termed the subgranular zone. Throughout life, they give rise to adult-born neurons in the dentate gyrus thereby contributing to learning and memory. Here, we report that neurons together with neural stem and precursor cells secrete the neurovascular protein epidermal growth factor-like protein 7 (EGFL7) to shape this niche. EGFL7 knock-out in vivo promoted adult neurogenesis generating neurons forming additional spines which permanently integrated into the neural circuit until old age. RNA-sequencing identified the cytokine VEGF-D as a major molecular driver of this process in vivo. In behavioral studies EGFL7 knock-out mice displayed stronger maintenance of memory suggesting longer-lasting spatial memory and improved memory consolidation in the hippocampus by modulation of pattern separation in young and aged mice. Taken together, EGFL7 is an upstream regulator of the VEGF-D in adult neurogenesis and a key regulator of learning and memory.

neuroscience↗

bioRxiv2021

NECAB2 orchestrates an endosomal pathway of mitochondrial quality control at striatal synapses

Synaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control and repair. We found that global knockout of the neuronal calcium-binding protein 2 (NECAB2) in the mouse causes loss of striatal synapses and behavioral phenotypes related to striatal dysfunction such as reduced motivation and altered sensory gating. Striatal mitochondria from Necab2 knockout mice are more abundant and smaller. They are characterized by increased respiration and superoxide production resulting in oxidative stress. This accumulation of dysfunctional mitochondria is caused by a defective assembly of mitochondria with early endosomes in a pathway that involves the small GTPase Rab5 and its guanine nucleotide exchange factor Alsin/ALS2. NECAB2 therefore participates in an endosomal pathway of mitochondrial stress response and repair important for striatal function.

neuroscience↗

bioRxiv2019

Soluble tubulin is locally enriched at mitotic centrosomes in C. elegans

During mitosis, the centrosome expands its capacity to nucleate microtubules. Understanding the mechanisms of centrosomal microtubule nucleation is, however, constrained by a lack of knowledge of the amount of soluble and polymer tubulin at mitotic centrosomes. Here we combined light microscopy and serial-section electron tomography to measure the amount of dimer and polymer at mitotic centrosomes in early C. elegans embryos. We show that a C. elegans one-cell stage centrosome at metaphase contains more than ten thousand microtubules with a total polymer concentration of 230 M. Centrosomes concentrate soluble /{beta} tubulin by about tenfold over the cytoplasm, reaching peak values of 470 M, giving a combined total monomer and polymer tubulin concentration at centrosomes of up to 660 M. These findings support in vitro data suggesting that microtubule nucleation in C. elegans centrosomes is driven in part by concentrating soluble tubulin.

cell biology↗

bioRxiv2018

Mutant Plasticity Related Gene 1 (PRG1) acts as a potential modifier in SCN1A related epilepsy

Plasticity related gene 1 encodes a cerebral neuron-specific synaptic transmembrane protein that modulates hippocampal excitatory transmission on glutamatergic neurons. In mice, homozygous Prg1-deficiency results in juvenile epilepsy. Screening a cohort of 18 patients with infantile spasms (West syndrome), we identified one patient with a heterozygous mutation in the highly conserved third extracellular phosphatase domain (p.T299S). The functional relevance of this mutation was verified by in-utero electroporation of a mutant Prg1 construct into neurons of Prg1-knockout embryos, and the subsequent inability of hippocampal neurons to rescue the knockout phenotype on the single cell level. Whole exome sequencing revealed the index patient to additionally harbor a novel heterozygous SCN1A variant (p.N541S) that was inherited from her healthy mother. Only the affected child carried both heterozygous PRG1 and SCN1A mutations. The aggravating effect of Prg1-haploinsufficiency on the epileptic phenotype was verified using the kainate-model of epilepsy. Double heterozygous Prg1-/+|Scn1awt/p.R1648Hmice exhibited higher seizure susceptibility than either wildtype, Prg1-/+, or Scn1awt/p.R1648H littermates. Our study provides evidence that PRG1-mutations have a potential modifying influence on SCN1A-related epilepsy in humans.

neuroscience↗