Guidepost cells | |
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Anatomical terminology |
Guidepost cells are cells which assist in the subcellular organization of both neural axon growth and migration. [1] They act as intermediate targets for long and complex axonal growths by creating short and easy pathways, leading axon growth cones towards their target area. [2] [3]
In 1976, guideposts cells were identified in both grasshopper embryos and Drosophila . [4] [5] [6] [7] Single guidepost cells, acting like "stepping-stones" for the extension of Ti1 pioneer growth cones to the CNS, were first discovered in grasshopper limb bud. [4] [6] However, guidepost cells can also act as a group. [4] There is a band of epithelial cells, called floor-plate cells, present in the neural tube of Drosophila available for the binding of growing axons. [4] These studies have defined guidepost cells as non-continuous landmarks located on future paths of growing axons by providing high-affinity substrates to bind to for navigation. [2]
Guidepost cells are typically immature glial cells and neuron cells, that have yet to grown an axon. [2] [4] [8] They can either be labeled as short range cells or axon dependent cells. [2]
To qualify as a guidepost cell, neurons hypothesized to be influenced by a guidance cell are examined during development. [9] To test the guidance cell in question, neural axon growth and migration is first examined in the presence of the guidance cell. [9] Then, the guidance cell is destroyed to further examine neural axon growth and migration in the absence of the guidance cell. [10] [9] If the neuronal axon extends towards the path in the presence of the guidance cell and loses its path in the absence of the guidance cell, it is qualified as a guidepost cell. [9] Ti1 pioneer neurons is a common example neurons that require guidepost cells to reach its final destination. [6] [9] They have to come in contact with three guidepost neurons to reach the CNS: Fe1, Tr1, and Cx1. [6] [9] When Cx1 is destroyed, the Ti1 pioneer is unable to reach the CNS. [6] [9]
The lateral olfactory tract (LOT) is the first system where guideposts cells were proposed to play a role in axonal guidance. [2] In this migrational pathway, olfactory neurons move from the nasal cavities to the mitral cells in the olfactory bulb. [2] The mitral primary axons extend and form a bundle of axons, called the LOT, towards higher olfactory centers: anterior olfactory nucleus, olfactory tubercle, piriform cortexr, entorhinal cortex, and cortical nuclei of the amygdala. [2] "Lot cells", the first neurons to appear in the telencephalon, are considered to be guideposts because they have cellular substrates to attract LOX axons. [2] To test their role in guidance, scientists ablated lot cells with a toxin called 6-OHDA. [2] As a result, LOT axons were stalled in the areas where lot cells were destroyed, which confirmed lot cells as guidepost cells. [2]
Cajal-Retzius cells [11] are the first cells to cover the cortical sheet and hippocampal primordium, and regulate cortical lamination by Reelin. [2] In order to make connections with GABAergic neurons in different regions of the hippocampus (stratum oriens, stratum radiatum, and inner molecular layer), pioneer entorhinal neurons make synaptic contacts with Cajal-Retzius cells. [2] To test their role in guidance, scientists (Del Rio and colleagues) ablated Cajal-Retzius cells with 6-OHDA. [2] As a result, entorhinal axons did not grow in the hippocampus and ruled Cajal-Retzius cells as guidepost cells. [2]
Perirecular cells (or internal capsule cells) are neuronal guidepost cells located along the path of creating the internal capsule. [2] They provide a scaffold for corticothalamic and thalamocortical axons (TCAs) to send messages to the thalamus. [2] There are transcription factors associated with perirecular cells: Mash1, Lhx2, and Emx2. When guidepost cells are mutated with knock out expressions of these factors, the guidance of TCAs are defected. [2]
Corridor cells are another set of guidepost cells present for TCA guidance. [2] These GABAergic neurons migrate to form a "corridor" between proliferation zones of the medial ganglionic eminence and globus pallidus. [2] Corridor cells provide TCA growth through MGE-derived regions.[ clarification needed ] However, the Neurgulin1 signaling pathway needs to be activated, with the expression of ErbB4 receptors on the surface of TCAs, for the connection to occur between corridor cells and TCAs. [2]
There are subpopulations of glial cells that provide guidance cues for axonal growth. [2] The first set of cells, called the "mid-line glial zipper", regulate the midline fusion and guidance of pioneer axons to the septum towards the contralateral hemisphere. [2] [7] The "glial sling" is a second set, located at the corticoseptal boundary, which provide cellular substrates for callosal axon migration across the dorsal midline. [2] [7] The "glial wedge" is made up of radial fibers, secreting repellent cues to prevent axons from entering the septum and positioning them towards the corpus callosum. [2] [7] The last set of glial cells, located in the induseum griseum, control the positioning of pioneer cingulate neurons in the corpus callosum region. [2]
An axon or nerve fiber is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.
Within a nervous system, a neuron, neurone, or nerve cell is an electrically excitable cell that fires electric signals called action potentials across a neural network. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.
The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.
Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately is an area of ongoing research.
Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word "netr", which means "one who guides". Netrins are genetically conserved across nematode worms, fruit flies, frogs, mice, and humans. Structurally, netrin resembles the extracellular matrix protein laminin.
The rostral migratory stream (RMS) is a specialized migratory route found in the brain of some animals along which neuronal precursors that originated in the subventricular zone (SVZ) of the brain migrate to reach the main olfactory bulb (OB). The importance of the RMS lies in its ability to refine and even change an animal's sensitivity to smells, which explains its importance and larger size in the rodent brain as compared to the human brain, as our olfactory sense is not as developed. This pathway has been studied in the rodent, rabbit, and both the squirrel monkey and rhesus monkey. When the neurons reach the OB they differentiate into GABAergic interneurons as they are integrated into either the granule cell layer or periglomerular layer.
A pioneer neuron is a cell that is a derivative of the preplate in the early stages of corticogenesis of the brain. Pioneer neurons settle in the marginal zone of the cortex and project to sub-cortical levels. In the rat, pioneer neurons are only present in prenatal brains. Unlike Cajal-Retzius cells, these neurons are reelin-negative.
The floor plate is a structure integral to the developing nervous system of vertebrate organisms. Located on the ventral midline of the embryonic neural tube, the floor plate is a specialized glial structure that spans the anteroposterior axis from the midbrain to the tail regions. It has been shown that the floor plate is conserved among vertebrates, such as zebrafish and mice, with homologous structures in invertebrates such as the fruit fly Drosophila and the nematode C. elegans. Functionally, the structure serves as an organizer to ventralize tissues in the embryo as well as to guide neuronal positioning and differentiation along the dorsoventral axis of the neural tube.
Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and oligodendrocytes. Their cell bodies (somata) reside in the embryonic ventricular zone, which lies next to the developing ventricular system.
Neuroregeneration involves the regrowth or repair of nervous tissues, cells or cell products. Neuroregenerative mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.
Pioneer axon is the classification given to axons that are the first to grow in a particular region. They originate from pioneer neurons, and have the main function of laying down the initial growing path that subsequent growing axons, dubbed follower axons, from other neurons will eventually follow.
A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.
The development of the nervous system in humans, or neural development, or neurodevelopment involves the studies of embryology, developmental biology, and neuroscience. These describe the cellular and molecular mechanisms by which the complex nervous system forms in humans, develops during prenatal development, and continues to develop postnatally.
The ganglionic eminence (GE) is a transitory structure in the development of the nervous system that guides cell and axon migration. It is present in the embryonic and fetal stages of neural development found between the thalamus and caudate nucleus.
Olfactory ensheathing cells (OECs), also known as olfactory ensheathing glia or olfactory ensheathing glial cells, are a type of macroglia found in the nervous system. They are also known as olfactory Schwann cells, because they ensheath the non-myelinated axons of olfactory neurons in a similar way to which Schwann cells ensheath non-myelinated peripheral neurons. They also share the property of assisting axonal regeneration.
Endogenous regeneration in the brain is the ability of cells to engage in the repair and regeneration process. While the brain has a limited capacity for regeneration, endogenous neural stem cells, as well as numerous pro-regenerative molecules, can participate in replacing and repairing damaged or diseased neurons and glial cells. Another benefit that can be achieved by using endogenous regeneration could be avoiding an immune response from the host.
Cellular adhesions can be defined as proteins or protein aggregates that form mechanical and chemical linkages between the intracellular and extracellular space. Adhesions serve several critical processes including cell migration, signal transduction, tissue development and repair. Due to this functionality, adhesions and adhesion molecules have been a topic of study within the scientific community. Specifically, it has been found that adhesions are involved in tissue development, plasticity, and memory formation within the central nervous system (CNS), and may prove vital in the generation of CNS-specific therapeutics.
The development of the cerebral cortex, known as corticogenesis is the process during which the cerebral cortex of the brain is formed as part of the development of the nervous system of mammals including its development in humans. The cortex is the outer layer of the brain and is composed of up to six layers. Neurons formed in the ventricular zone migrate to their final locations in one of the six layers of the cortex. The process occurs from embryonic day 10 to 17 in mice and between gestational weeks seven to 18 in humans.
A follower neuron is a nerve cell that arises in the developmental stage of the brain and which growth and orientation is intrinsically related to pioneer neurons. These neurons can also be called later development neurons or follower cells. In the early stages of brain development, pioneer neurons define axonal trajectories that are later used as scaffolds by follower neurons, which project their growth cones and fasciculate with pioneer axons, forming a fiber tract and demonstrating a preference for axon-guided growth. It is thought that these neurons can read very accurate cues of direction and fasciculate or defasciculate in order to reach their target, even in a highly dense axon bundle.
Jeffrey D. Macklis is an American neuroscientist. He is the Max and Anne Wien Professor of Life Sciences in the Department of Stem Cell and Regenerative Biology and Center for Brain Science at Harvard University, Professor of Neurology [Neuroscience] at Harvard Medical School, and on the Executive Committee and a Member of the Principal Faculty of the Neuroscience / Nervous System Diseases Program at the Harvard Stem Cell Institute.
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