Prader-Willi is caused by either deletions, failure in imprinting, or monosomy/disomy 15 from the father’s side. The genes involved are known to include, but are not known to be limited to SNRPN and NDN. NDN odes for the protein Necdin, which, in rodents, interacts with neurotrophin receptors in a way that is not completely understood to promote normal cognitive development. SNRPN codes for several products, including small nucleolar RNAs, a splicing factor involved in RNA processing, and a polypeptide known as SNURF. The precise role of this gene is unknown.
. Embryonic stem cells have been identified by scientist as a type of stem cell that can advance regenerative medicine. The potential of regenerative medicine ranges from allowing pancreatic cells to produce insulin for diabetics to reconnecting the nerves in severed spinal cords. However, the greatest potential embryonic stem cells presents are its ability to change into any of the more than 200 different cell types in the body. This ability to change into any cell type can produce cures for Alzheimer’s disease, Parkinson’s disease, or any of the other conditions that stem cell therapy might help therefore improving the lives of those who live with these
How are medially-positioned progenitors affected by diffusible signals? The number of neurons belonging to populations found near or at the centre of the dorsoventral axis of the cord is influenced by signal levels, including Shh and BMPs. A moderate concentration of BMP signaling is needed to generate the correct number of medial interneurons. In zebrafish mutants in which a particular BMP protein is functionally reduced, there was a resulting increase in Lim1+ interneurons (medial interneurons) post-mitotically (Nguyen et al., 2000). Interestingly, further BMP reduction decreases medial interneuron counts, illustrating the fine balance of BMP levels that is needed to establish appropriate medial interneuron expression. Perturbing natural
During embryogenesis, MeCP2 levels are relatively low in the brain, however, in the postnatal period of neural development, a progressive increase in expression is seen from deep cortical layers to the superficial layers of the brain (Sala & Pizzorusso, 2013). MeCP2’s ability to bind DNA sequences methylated at cytosine 5’CpG and its high affinity for AT-rich DNA sequences allows it to compact chromatin and impact the ability of other nuclear proteins to interact with DNA (Pohodich & Zoghbi, 2015). Accordingly, MeCP2 function has been shown as a primary regulator of neurogenesis modulation and synaptic development, as well as intricately involved in neuronal function and maintenance (Jin, et al., 2017). In various MeCP2-deficient models, neurons displayed a decreased quantity of axons and dendrites along with reduced cortical neurite complexity (Jin, et al., 2017). Likewise, in vitro, MeCP2-deficient stem cells exhibited impaired neural differentiation and more rapid senescence compared to controls, thereby confirming the crucial role of MeCP2 in corticogenesis and neuronal maturation (Jin, et al., 2017). Almost all cases (99.5%) of RTT result from a de novo mutation of the MeCP2 gene which is located within Xq28 (Pohodich & Zoghbi, 2015). The remaining 0.5% of cases are familial where the mutation is inherited from the mother with germline mosaicism or favorable X-chromosome inactivation that results in her being
Stem cell lines were derived from Mus musculus castaneus x Mus musculus (C57Black6) F1 embryos, because polymorphism between these strains allow for the examination of mono-allelic patterns of epigenetic marks and gene expression within loci is regulated by genomic imprinting. Cells were grown on Mytomycin C treated feeder mouse fibroblast layer, then moved to a feeder free system. Embryonic stem cells (ES) were used to test the stability of the candidate gene during differentiation, Trophectoderm stem cells (TS) were used to test ethanol exposure on placentation, and Neurosphere stem cells were used to model neuroblast migration from their germinal zones to colonize brain development in in vitro. Cells were cultured to an 80% confluence and dissociated with 1xTrypsin. All cells, except control group, were cultures with ethanol at varying concentrations of: 60mg/dL, 120mg/dL, and 320mg/dL. Cells were extracted at each stage of neurosphere differentiation. Total RNA was isolated using the Trizol method for 4 independent experimental replicates. The samples were then DNased using DNaseI and made into 4 independent cDNA reactions using the reverse-transcription kit, SuperScriptII, and random hexamer oligonucleotides. Quantitative real-time PCR was performed using DyNAmo Flash SYBR Green qPCR Mastermix on a 7500 Fast Real-Time PCR System from Applied Biosystems in 3 independent reactions measuring the candidate genes in duplicates. The data was then
Studies on nerve fibers’ longitudinal growth, axons’ regeneration and structural plasticity of axons and dendrites illustrated that they are restricted to short distances and limited spatial dimensions in the CNS. Scientists recognized that neural repair required plasticity, sprouting, and regeneration, which was limited within the adult CNS. However, once adult CNS axons from multiple areas successfully regenerated into peripheral nerve grafts in the spinal cord, brain, or optic nerve, scientists discovered the key role of local tissue microenvironment in determining the extent of growth. Scientists discovered neurite growth inhibitor factors enriched in myelin such as Nogo-A, myelin proteins, MAG and OMgp, semaphorins and ephrins, and chondroitin sulphate
In the first part of the present thesis, by doing gain and loss of function studies Irene demonstrates that high levels of Shh and Smad1-5 signaling pathway activation regulate progenitor and stem cell proliferative mode of division, while the loss of function studies promoted to neuronal differentiation. In addition to this, Irene also reports the involvement of the midline signal Shh in the zebrafish neurulation; she discovered that Shh signal is sufficient to duplicate or change lumen position.
Emerging evidence implicates microglial play critical roles to the CNS development of the brain. Microglial are unique population arise from immature yolk-sac macrophages that migrate and colonize the developing brain (Ginhoux et al.,
Scientists have discovered that interneurons are responsible for the majority of new brain growth. They hope that the discovery that neurons can grow in the adult brain will allow for advancements in neuroplasticity research, such as determining the conditions necessary for this growth to occur. Dr. Nedivi, one of the scientists on the project, stated, “If we can identify what aspect of this location allows growth in an otherwise stable brain, we can perhaps use it to coax growth in cells and regions that are normally unable to repair or adjust to a changing
The development of the cortex is a delicate balance between proliferation, differentiation and migration of neural progenitors (NPs). Throughout developmental process, various cellular mechanisms ensure that NPs are differentiating into the correct cell subtypes, migrating to their correct regions, and forming the correct cortical and sub-cortical layers. The cortex is comprised of both excitatory and inhibitory neurons, which interact within neuronal circuits to mediate cortical functions. Though both types of neurons reside in the cortex, they arise from different embryonic brain regions, and from different neural progenitors. Excitatory neurons are generated from neural progenitors residing in the ventricular zone (VZ)/subventricular
Glial cells are the most numerous cells in the brain, outnumbering neurons nearly 3:1, although smaller and some lacking axonal and dendritic projections. Once thought to play a subpar role to neurons, glial cells are now recognized as responsible for much greater functions. There are many types of glial cells, including: oligodendrocytes, microglia, and astrocytes. Oligodendrocytes form the myelin sheath in the CNS, by wrapping themselves around the axons of neurons. Their PNS counterpart, Schwann cells, are also considered glial cells. This sheath insulates the axon and increases the speed of transmission, analogous to the coating on electrical wires. Microglia are considered to be “immune system-like”; removing viruses, fungi, and other wastes that are present. Astrocytes, however, are considered to be the most prominent. Their functions span throughout the brain, including, but not limited to: the synchronization of axonal transmission via G-protein-coupled receptors, blood flow regulation via the dilation of blood vessels, and the performance of reactive gliosis in conjunction with microglia. Both astrocytes and oligodendrocytes develop from neuroepithelial cells. Other types of glial cells include Radial glia, which direct immature neuron migration during development.
The Role of Angioneurins in Neurodegeneration, adapted from the original table by Zacchigna et al, 2008 (28)
In addition, we wanted to assess whether astrocytes, the main ECM producers in the brain, become reactive already during this early stage of AD-like disease, thereby possibly contributing to the observed ECM alterations. Our preliminary results suggest no change in the expression of basigin, a downregulation of versican and tenascin-R, and an upregulation of HAPLN1 and glial fibrillary acidic protein (GFAP) in the hippocampus of APP/PS1 mice at 3 months (early AD). Although these changes are not completely in line with previously reported ECM alterations, we do find changes in hippocampal ECM in 3 months old APP/PS1 mice that may contribute to alterations in cell communication, neuronal survival, and synaptic function and plasticity. In addition, the observed increase in GFAP expression in the hippocampus of 3 months old APP/PS1 mice and in isolated hippocampal astrocytes in vitro suggests that astrogliosis precedes amyloid plaque deposition, thus astrocytes possibly play a role in early ECM
In this essay, the role of Chordin in the Spemann’s organiser will be examined, as well as an outline of the Spemann Organiser’s discovery and formation in neural tissue. Chordin has a role in antagonising BMP, forming the dorsal-ventral axis, but it can be controlled if excess Chordin activation occurs. These aspects of Chordin will be examined throughout the following essay.