Dendrite development - Essays answers for all previous questions on this topic PDF

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Dendrite development 2015 Write an essay on dendrite development. In 1988, Ramon y Cajal identified dendrites on the surface of Purkinje cells with thorns and short spines. Since then, dendrites have been defined as highly branched projections originating from the cell soma which transmit postsynaptic potentials from their dendritic spines. These projections are crucial for information processing following synaptic neurotransmission. A neuron can have thousands of dendritic spines which are small protrusions from the dendrites and only one axon. The dynamic of dendrites’ remodeling with neuronal activity underpins the ability that neurons have to constantly adapt and respond to external stimuli. The development of dendrites is based on the constant interactions with neurons and glia where the branching pattern and position of dendritic arbor determine how neurons receive and integrate inputs. The types of contacts between dendrites and presynaptic terminals are varied due to their sizes and orientation. Their size and orientation regulate how many synaptic inputs the neuron can receive and the types and number of sources from which it can receive synaptic connections respectively. During development, it is observed that neurons have a ‘top’ end from which apical dendrites emerge and a ‘bottom’ end from which basal dendrites emerge. These dendrites are found throughout the cortex but each has a specific morphology. Apical dendrites in pyramidal neurons are observed as a conical spray of longer dendrites, while basal dendrites appear as a cluster of shorter dendrites. As mentioned above, one of the key structures of dendrites are spines. Dendritic spines receive input from a single excitatory presynaptic terminal which is the case for most glutamatergic synapses. Because dendritic spines are the sites of connection between neurons and critical neurotransmitters for processing information, specific regulation is essential. A dendritic spine consists of three core parts; the spine base, neck and head. The development of dendritic spines progresses through a number of stages. First, dendrites typically develop without dendritic spines. Second, finger-like protrusions called filopodia emerge from along the dendrite during synaptogenesis. It is thought that filopodia recruit early axons and then develop into dendritic spines which are formed early in postnatal life. Dendritic arborization (branching) is a process by which neurons form new dendritic branches to create new synapses and is regulated by four critical mechanisms. First, genetic studies in the dendritic arborization of dopaminergic sensory neuron in Drosophila identified core transcriptional programs controlling

dendrite development. Four classes of dopaminergic neurons based their location and branching pattern were identified. Class 1 and 2 underline simple branching patterns with small dendritic fields, while class 3 and 4 underline complex branching patterns with large dendritic fields. This finding led to the discovery of transcription factors such as Cut which controls class-specific dendritic branching patterns of dopaminergic neurons. Class 3 and 4 are associated with higher levels of Cut, while class 1 and 2 are associated with no or low levels of Cut expression. Therefore, specific transcription factors establish the basic dendritic morphology of distinct neuronal classes. Second, important extracellular cues interact with signaling pathways to sculpt dendritic morphology. This second mechanism is in conjunction with the third mechanism which underlines the coordinate sculpting of axons and dendrites resulting in neuronal circuits formation. The dynamics of dendritic arborization requires global architectural modifications such as general growth and local structural changes such as sprouting/retraction of branches. Local branch dynamics can be observed using imaging techniques at short intervals (hours), however growth that contribute to global changes are seen at long intervals (day). Dendrite arborization is developed gradually following addition, retraction and extension of branches. However, altogether there are more branches that are added than maintained. Similarly to growth cones, the major components of dendritic spines’ cytoskeleton are actin and microtubules which can be affected by Rho GTPases such as Cdc42, Rec1 and RhoA. These Rho GTPases are activated by glutamatergic synaptic input which changes the cytoskeleton dynamics and directly alter the dendritic arbor development. Each of these GTPases has a specific role in dendritic arbor development and are active when GTP-bound but not when GDP-bound. RhoA controls the stabilization of microtubules and actin polymerization in order to regulate the extension of dendritic branches. Rac mediates actin and microtubule dynamics in order to regulate branch dynamics. Neurotrophic factors such as neurotrophin increase dendritic complexity of pyramidal neurons by binding to Trk (tyrosine kinase) receptors. However, some neurotrophins only affect arborization in specific areas as BDNF does not affect it in tectal neurons. The activation of Trk receptors results in regulation of MAP kinase and PI-3 kinase pathways, but also by regulating Rho GTPasemediated cytoskeletal dynamics. Morphogens such as Bone Morphogenetic proteins (BMPs) and Wnt also play a critical role in regulating denrite arbor development. BMP7 increases the growth and branching of cortical neuron dendrtites. Similarly Wnt7b controls the dendritic arborization of hippocampal neurons by binding to Frizzed receptors which activate the scaffold protein dischevelled (Dvl) which in turns activates Rac and Jnk. The activation of Jnk enhances dendritic development.

Fourth, electrical and synaptic activity play a critical role in arborization as synapse formation and dendritic growth occur simultaneously. Studies focused on glutamatergic synapse formation which is acquired after multiple stages. As the activity of NMDA increases, the number of AMPA receptors at the synapse increases too resulting in stabilization of branching. On the other hand, less activity results in less AMPA receptors and therefore the dendrites retract. Synapses containing both AMPA and NMDA receptors have an increase in calcium influx which enhances branch stabilization and addition. This demonstrates that dendritic development is an activity-dependent process.

They develop due to extracellular cues interacting with signaling pathways which sculpts different dendritic morphology. Morphological changes can occur rapidly in response to synaptic input or growth factors. Imaging studies have shown that short intervals display local branch dynamics and growth that contribute to global changes in dendritic architecture seen at long intervals. This indicates that dendrite arbor develops gradually due to addition, retraction, stabilisation and extension of branches. Dendritic spines have been associated with synaptic plasticity in the central nervous system similarly to glutamatergic neurotransmission. Indeed, there are a number of different dendritic spines found in the cortex which can change by altering their actin cytoskeleton. Spines maturity progresses from long, thin filopodia type structure to wideheaded mushroom spines and branched spines (more rarely).

Techniques such as golgi cox staining have been used to identify the dendritic branching of pyramidal neurons under an electron microscope. Dendrite pathology: Fragile X syndrome and Fmr1 KO - This study demonstrated the rationale behind studying the basic biological mechanisms that control dendrite development - Understanding the molecules that control the function and dysfunction of dendrites provides insghts into the pathology of neurodevelopmental disorders such as autism spectrum disorder

2015 Describe the molecular and cellular mechanisms involved in the development of dendrites during the development of the nervous system. Fragile X syndrome (FXS) is the most inherited form of autism and intellectual disability, and is caused by the expansion of a CGG trinucleotide repeat in the Fragile X mental retardation 1 (Fmr1) gene. FXS patients have 200 or more CGG repeats in the 5’UTR region leading to the hypermethylation and transcriptional silencing of the Fmr1 gene (no Fmr1 protein is translated). The general population has either short repeat sequence (...