Guidepost cells are cells which assist in the subcellular organization of both neural

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

growth and migration. They act as intermediate targets for long and complex axonal growths by creating short and easy pathways, leading axon

growth cone A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago ...

s towards their target area.

Identification

In 1976, guideposts cells were identified in both grasshopper embryos and ''

Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...

''. 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. However, guidepost cells can also act as a group. There is a band of

epithelial cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

, called floor-plate cells, present in the

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, ...

of Drosophila available for the binding of growing axons. 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. Guidepost cells are typically immature

glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...

and neuron cells, that have yet to grown an axon.Colón-Ramos DA, Shen K, 200
Cellular Conductors: Glial Cells as Guideposts during Neural Circuit Development.
PLoS Biol 6(4): e112. They can either be labeled as short range cells or axon dependent cells. To qualify as a guidepost cell,

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s hypothesized to be influenced by a guidance cell are examined during development. To test the guidance cell in question, neural axon growth and migration is first examined in the presence of the guidance cell. Then, the guidance cell is destroyed to further examine neural axon growth and migration in the absence of the guidance cell. 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. Ti1

pioneer neuron 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 ...

s is a common example neurons that require guidepost cells to reach its final destination. They have to come in contact with three guidepost neurons to reach the CNS: Fe1, Tr1, and Cx1. When Cx1 is destroyed, the Ti1 pioneer is unable to reach the CNS.

Roles in formation

Lateral olfactory tract

The lateral olfactory tract (LOT) is the first system where guideposts cells were proposed to play a role in axonal guidance. In this migrational pathway, olfactory neurons move from the nasal cavities to the mitral cells in the

olfactory bulb The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OF ...

. The mitral primary axons extend and form a bundle of axons, called the LOT, towards higher olfactory centers:

anterior olfactory nucleus The anterior olfactory nucleus (AON) also called the anterior olfactory cortex, is a major early processing area for olfaction located behind the olfactory bulb, and in the olfactory tract (olfactory peduncle). The AON connects the olfactory pro ...

olfactory tubercle The olfactory tubercle (OT), also known as the tuberculum olfactorium, is a multi-sensory processing center that is contained within the olfactory cortex and ventral striatum and plays a role in reward cognition. The OT has also been shown to ...

piriform cortex The piriform cortex, or pyriform cortex, is a region in the brain, part of the rhinencephalon situated in the cerebrum. The function of the piriform cortex relates to the sense of smell. Structure The piriform cortex is part of the rhinencephal ...

entorhinal cortex The entorhinal cortex (EC) is an area of the brain's allocortex, located in the medial temporal lobe, whose functions include being a widespread network hub for memory, navigation, and the perception of time.Integrating time from experience in t ...

, and cortical nuclei of the

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

. "Lot cells", the first neurons to appear in the

telencephalon The cerebrum (: cerebra), telencephalon or endbrain is the largest part of the brain, containing the cerebral cortex (of the two cerebral hemispheres) as well as several subcortical structures, including the hippocampus, basal ganglia, and olf ...

, are considered to be guideposts because they have cellular substrates to attract LOX axons. To test their role in guidance, scientists ablated lot cells with a toxin called 6-OHDA. As a result, LOT axons were stalled in the areas where lot cells were destroyed, which confirmed lot cells as guidepost cells.

Entorhinal projections

Cajal-Retzius cells are the first cells to cover the cortical sheet and hippocampal primordium, and regulate cortical lamination by

Reelin Reelin, encoded by the ''RELN'' gene, is a large secreted extracellular matrix glycoprotein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this importa ...

. In order to make connections with GABAergic neurons in different regions of the

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

(

stratum oriens Hippocampus anatomy describes the physical aspects and properties of the hippocampus, a neural structure in the medial temporal lobe of each cerebral hemisphere of the brain. It has a distinctive, curved shape that has been likened to the se ...

, stratum radiatum, and inner molecular layer), pioneer entorhinal neurons make synaptic contacts with Cajal-Retzius cells. To test their role in guidance, scientists (Del Rio and colleagues) ablated Cajal-Retzius cells with 6-OHDA. As a result, entorhinal axons did not grow in the hippocampus and ruled Cajal-Retzius cells as guidepost cells.

Thalamocortical connections

Perirecular cells (or internal capsule cells) are neuronal guidepost cells located along the path of creating the

internal capsule The internal capsule is a paired white matter structure, as a two-way nerve tract, tract, carrying afferent nerve fiber, ascending and efferent nerve fiber, descending axon, fibers, to and from the cerebral cortex. The internal capsule is situate ...

. They provide a scaffold for corticothalamic and thalamocortical axons (TCAs) to send messages to the

thalamus The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...

. There are

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

s 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. Corridor cells are another set of guidepost cells present for TCA guidance. These GABAergic neurons migrate to form a "corridor" between proliferation zones of the medial ganglionic eminence and

globus pallidus The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a major component of the Cerebral cortex, subcortical basal ganglia in the brain. It consists of two adjacent segments, one external (or lateral), known in rodents simpl ...

. Corridor cells provide TCA growth through MGE-derived regions. 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.

Corpus callosum

There are subpopulations of

that provide guidance cues for axonal growth. The first set of cells, called the "mid-line glial zipper", regulate the midline fusion and guidance of

pioneer axon 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 foll ...

s to the septum towards the contralateral hemisphere. The "glial sling" is a second set, located at the corticoseptal boundary, which provide cellular substrates for callosal axon migration across the dorsal midline. The "glial wedge" is made up of radial fibers, secreting repellent cues to prevent axons from entering the

septum In biology, a septum (Latin language, Latin for ''something that encloses''; septa) is a wall, dividing a Body cavity, cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate. Examples Hum ...

and positioning them towards the

corpus callosum The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental ...

. The last set of glial cells, located in the induseum griseum, control the positioning of pioneer cingulate neurons in the

region.

References

External links

COPE entry on guidepost cells
{{DEFAULTSORT:Guidepost Cells Developmental neuroscience