Guidepost cells are cells which assist in the subcellular organization of both neural axon growth and migration. 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.

Identification

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

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species ...

''. 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 one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

, called floor-plate cells, present in the neural tube 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 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, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

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 neurons 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 Mitral cells are neurons that are part of the olfactory system. They are located in the olfactory bulb in the mammalian central nervous system. They receive information from the axons of olfactory receptor neurons, forming synapses in neuropils ...

in the

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

. 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 portion of the forebrain of vertebrates. It is involved in olfaction and has supposedly strong influence on other olfactory areas like the olfactory bulb and the ...

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 cortexr,

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 the ...

, and cortical nuclei of the

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...

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

telencephalon The cerebrum, 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 olfactory bulb. In ...

, 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 Oxidopamine, also known as 6-hydroxydopamine (6-OHDA) or 2,4,5-trihydroxyphenethylamine, is a neurotoxic synthetic organic compound used by researchers to selectively destroy dopaminergic and noradrenergic neurons in the brain. The main use for ...

. 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 import ...

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

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

(

stratum oriens Hippocampus anatomy describes the physical aspects and properties of the hippocampus, a neural structure in the medial temporal lobe of the brain. It has a distinctive, curved shape that has been likened to the sea-horse monster of Greek mythol ...

stratum radiatum In geology and related fields, a stratum ( : strata) is a layer of rock or sediment characterized by certain lithologic properties or attributes that distinguish it from adjacent layers from which it is separated by visible surfaces known as ei ...

, and

inner molecular layer Interior may refer to: Arts and media * ''Interior'' (Degas) (also known as ''The Rape''), painting by Edgar Degas * ''Interior'' (play), 1895 play by Belgian playwright Maurice Maeterlinck * ''The Interior'' (novel), by Lisa See * Interior de ...

), 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

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

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...

. 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 of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

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 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 nuc ...

and

globus pallidus The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a subcortical structure of the brain. It consists of two adjacent segments, one external, known in rodents simply as the globus pallidus, and one internal, known in rod ...

. 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 glial cells 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 follo ...

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 for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate. Examples Human anatomy * Interatri ...

and positioning them towards the corpus callosum. The last set of glial cells, located in the induseum griseum, control the positioning of pioneer cingulate neurons in the corpus callosum region.

References

External links

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