Search results for " mammalia"
showing 10 items of 126 documents
Loss of desmoglein 2 suggests essential functions for early embryonic development and proliferation of embryonal stem cells.
2002
Summary Desmoglein 2 (Dsg2) is a Ca 2+ -dependent adhesion molecule of desmosomes and is synthesized in all desmosome-bearing tissues from their earliest appearance onward. To examine the function of Dsg2, its gene was inactivated by homologous recombination in embryonal stem (ES) cells for the generation of knockout mice. DSG2 −/− mice and a considerable number of DSG2 +/− mice died at or shortly after implantation. On the other hand, DSG2 −/− blastocysts developed an apparently normal trophectoderm layer, the first tissue known to produce desmosomes, and hatched properly. Immunofluorescence analyses of these blastocysts showed, however, that the distribution of the desmosomal plaque prote…
A protein quality control pathway regulated by linear ubiquitination.
2019
Neurodegenerative diseases are characterized by the accumulation of misfolded proteins in the brain. Insights into protein quality control mechanisms to prevent neuronal dysfunction and cell death are crucial in developing causal therapies. Here, we report that various disease-associated protein aggregates are modified by the linear ubiquitin chain assembly complex (LUBAC). HOIP, the catalytic component of LUBAC, is recruited to misfolded Huntingtin in a p97/VCP-dependent manner, resulting in the assembly of linear polyubiquitin. As a consequence, the interactive surface of misfolded Huntingtin species is shielded from unwanted interactions, for example with the low complexity sequence doma…
PBX1 acts as terminal selector for olfactory bulb dopaminergic neurons
2020
15 páginas, 8 figuras. Supplementary information available online at http://dev.biologists.org/lookup/doi/10.1242/dev.186841.supplemental
Low Density Lipoprotein Receptor-related Protein 1 (LRP1) Modulates N-Methyl-d-aspartate (NMDA) Receptor-dependent Intracellular Signaling and NMDA-i…
2013
The lipoprotein receptor LRP1 is essential in neurons of the central nervous system, as was revealed by the analysis of conditional Lrp1-deficient mouse models. The molecular basis of its neuronal functions, however, is still incompletely understood. Here we show by immunocytochemistry, electron microscopy, and postsynaptic density preparation that LRP1 is located postsynaptically. Basal and NMDA-induced phosphorylation of the transcription factor cAMP-response element-binding protein (CREB) as well as NMDA target gene transcription are reduced in LRP1-deficient neurons. In control neurons, NMDA promotes γ-secretase-dependent release of the LRP1 intracellular domain (LRP1-ICD). However, pul…
PSCDGs of mouse multipotent adult germline stem cells can enter and progress through meiosis to form haploid male germ cells in vitro
2010
Spermatogonial stem cells (SSCs) provide the basis for spermatogenesis throughout adult life by undergoing self-renewal and differentiation into sperm. SSC-derived cell lines called multipotent adult germline stem cells (maGSCs) were recently shown to be pluripotent and to have the same potential as embryonic stem cells (ESCs). In a differentiation protocol using retinoic acid (RA) and based on a double selection strategy, we have shown that ESCs are able to undergo meiosis and produce haploid male germ cells in vitro. Using this differentiation protocol we have now succeeded to generate haploid male germ cells from maGSCs in vitro. maGSCs derived from a Stra8-EGFP transgenic mouse line wer…
The Cannabinoid Receptor CB1 Interacts with the WAVE1 Complex and Plays a Role in Actin Dynamics and Structural Plasticity in Neurons.
2015
The molecular composition of the cannabinoid type 1 (CB1) receptor complex beyond the classical G-protein signaling components is not known. Using proteomics on mouse cortex in vivo, we pulled down proteins interacting with CB1 in neurons and show that the CB1 receptor assembles with multiple members of the WAVE1 complex and the RhoGTPase Rac1 and modulates their activity. Activation levels of CB1 receptor directly impacted on actin polymerization and stability via WAVE1 in growth cones of developing neurons, leading to their collapse, as well as in synaptic spines of mature neurons, leading to their retraction. In adult mice, CB1 receptor agonists attenuated activity-dependent remodeling o…
Thyroid hormone deficiency disrupts rat eye neurodevelopment
2010
Clinical and experimental studies have highlighted the role played by thyroid hormones (TH) in neural and neuro-sensorial development. However, knowledge on TH mechanisms on the developing visual system is still incomplete. To uncover TH actions on the eyes and vision we carried out a microscopical study on the role of TH in the developing retina and optic nerve, in a rat model of controlled TH deficiency (THD). Morphometric and stereological analyses of the retina and optic nerve showed a reduction in the volume of the eye (p<0.001) and optic nerve cross-sectional area (p<0.001), and thinning of the retinal layers (p<0.001). Glial development and myelination was significantly delayed in th…
A critical period for experience-dependent remodeling of adult-born neuron connectivity.
2015
Neurogenesis in the dentate gyrus (DG) of the adult hippocampus is a process regulated by experience. To understand whether experience also modifies the connectivity of new neurons, we systematically investigated changes in their innervation following environmental enrichment (EE). We found that EE exposure between 2-6 weeks following neuron birth, rather than merely increasing the number of new neurons, profoundly affected their pattern of monosynaptic inputs. Both local innervation by interneurons and to even greater degree long-distance innervation by cortical neurons were markedly enhanced. Furthermore, following EE, new neurons received inputs from CA3 and CA1 inhibitory neurons that w…
Increase in Bcl-2 phosphorylation and reduced levels of BH3-only Bcl-2 family proteins in kainic acid-mediated neuronal death in the rat brain.
2003
Kainic acid induces excitotoxicity and nerve cell degeneration in vulnerable regions of rat brain, most markedly in hippocampus and amygdala. Part of the cell death following kainic acid is apoptotic as shown by caspase 3 activation and chromatin condensation. Here we have studied the regulation of pro- and anti-apoptotic proteins belonging to the Bcl-2 family in rat hippocampus and amygdala by kainic acid in relationship to ensuing neuronal death. The pro-apoptotic protein Bax was up-regulated in hippocampus 6 h after kainic acid administration. The increase in Bax was followed by the appearance of TdT-mediated dUTP nick end labelling-positive cells which were prominent at 24 h. Immunohist…
Fetuin-B, a liver-derived plasma protein is essential for fertilization.
2013
SummaryThe zona pellucida (ZP) is a glycoprotein matrix surrounding mammalian oocytes. Upon fertilization, ZP hardening prevents sperm from binding to and penetrating the ZP. Here, we report that targeted gene deletion of the liver-derived plasma protein fetuin-B causes premature ZP hardening and, consequently, female infertility. Transplanting fetuin-B-deficient ovaries into wild-type recipients restores fertility, indicating that plasma fetuin-B is necessary and sufficient for fertilization. In vitro fertilization of oocytes from fetuin-B-deficient mice only worked after rendering the ZP penetrable by laser perforation. Mechanistically, fetuin-B sustains fertility by inhibiting ovastacin,…