Communication between neurons and glia in Drosophila

The glia cells of Drosophila are easily studied at all developmental levels as they contain many markers that allow for the manipulation of the cell subtypes. Drosophila gliaa are very similar to the mammalian equivalents in developmental, morphological, functional and quite possibly their molecular criteria. Glia are nonneural.

There are three types of glia that communicate with the neurons are:

1. Cortex glia (structurally similar to the astrocytes in mammals) and are in close contact with the neurons.

2. Neuropil glia (similar to oligodendrocytes)

3. Peripheral glia (similar to Schwann cells)

Signalling in Developing Neurons and Glia

Clusters of ectodermal cells that have proneural genes promote the formation of neuroblasts. The cell interactions are regulated by ligand-receptor signalling called Delta and Notch respectively so that only one cell becomes a neuroblast (control of cell sibling fate along with the Numb protein). They function on the MP2 precursor. Neuroblasts are the equivalent of neural stem cells in higher organisms.

Neuroblasts can divide asymmetrically to give a series of ganglion mother cells.Each of these can then give rise to two neurons or glia.

      N.B. What is Delta Notch Signaling?

       Cells that express Delta, Jagged or Serrate proteins in their cell membranes  can activate neighbouring cells that contain the Notch receptor protein in their membrane. Notch is a transmembrane protein and when complexed to one of these ligands it undergoes a conformational change that allows a protease to cut it. The cleaved part an now enter the nucleus and bind to a dormant transcription factor that will now become activated and activate the target genes.

Delta-Notch signaling

Delta-Notch signaling

Notch regulates cell fate, proliferation and death in many organs and cell types. It plays a significant role in the fate of sibling cells in the CNS by activating differential gene expression in the sibling cells that result from asymmetric cell division.

In Drosophila, Notch signaling plays a major role in  neurogenesis:

1. It is critical in the phase where the neuroblasts are taken fro the neuroectoderm

2. Functions along with asymmetric cell division to regulate cell fate of sibling cells.

Notch serves as a repressor to most equally potent cells in the ectoderm that can become neuroblasts, forcing most to become ectodermal cells instead by repression of the proneural genes.

The MP2 precursor divides asymmetrically to give a larger dorsal neuron dMP2, and a small ventral neuron, vMP2. Without Delta-Notch signalling, the vMP2 will become another dMP2.

The colocalization of Notch-Delta as “dots” on the ectoderm, mesoderm,, neuroblasts and dMP2 and vMP2 neurons may represent internal clearing of the elta-Notch protein. Both dMP2 and vMP2 neurons show the Notch receptor and adjacent cells show the Delta ligand. The Numb protein can interfere with the cell fate of vMP2 which shows that the cell fate of vMP2 is determined by extrinsic Delta-Notch signalling rather than lateral signaling which is usually associated with groups of cells that show Delta-Notch signaling.

Communication among Glial cells and between Glial and Neurons.

Two way communication between the neurons and glia is necessary for the normal functioning of the nervous system of Drosophila. Signals between neurons and glia include: ion fluxes, neurotransmitters, cell adhesion and specialized signaling molecules.

Glial cells communicate with each other using intracellular waves of Ca2+ via other chemical messengers.

This signaling allows glia to regulate synapse formation and control the synaptic strength.

Cortex glia – Cortex glia Communication

These communicate via gap junctions which allow ions and small molecules to pass freely between the cells. These gap junctions work with the extracellular signaling methods to allow fro the rapid propagation of signals.

Large amounts of extracellular glutamate ( a neurotransmitter) signals the Cortex glia that a large signal is being transmitted by the neuron. This changes the levels of Ca2+ in the glia cytoplasm and ATP is also secreted (mechanism unknown). This ATP will then go to neighbouring cortex glia and activate their P2Y receptors which generate an increase in intracellular Ca2+ levels that will spread to neighbouring Cortex glia via the gap junctions allowing the signal to resonate rapidly through the brain.

GLIAL REGULATION AND STRENGTH

The cortex glia releases glutamate via membrane specific associated channels or transporters which are synthesized from precursors molecules such as N-acetylaspartylglutamate. It involves neurotransmitters such as GABA and proteins/ polypeptide chains may play a key role in neuron-glial signaling. An example may be that Serine that the astrocytes release may stimulate NMDA receptors found on the postsynaptic membrane of neurons to activate the glycine found on the surface on the NMDA . As such the serine may be an ligand that acts as a regulatory device for the NMDA receptors of postsynaptic neurons.

GLIAL- NEURON COMMUNICATIONS

When signaling pathways are activated by the calcium it dictates the transcription of genes that are involved in regulation and variation of peripheral glia This process of communication between the axon and glial cells aid in terminating the division of peripheral glia until their in an active and functional nervous system
The glia as such have an important role in setting up the framework of the brain. When neurons interact with specific cell adhesion molecules exclusively found on the on the membrane of the glial , the neurons subsequently move along glial processes and they extend axons and dendrites using glia to aid in forming a synapse as well as transmission.

Astrocytes communicate with adjacent astrocytes via gap junctions (GJ) and with distant astrocytes via extracellular ATP. The rise in Ca2+ causes release of glutamate from astrocytes, and ATP is released via an unknown mechanism, which propagates ATP signaling to adjacent cells. Astrocytes may also regulate synaptic transmission by uptake of glutamate from the synaptic cleft via membrane transporters (green arrow) or the release of glutamate upon reversal of the transporter induced by elevated intracellular Na+

Cortex glia communicate with adjacent glia through gap junctions  and with
distant ones by extracellular ATP. The rise in Ca2+ causes release of glutamate from
cortex glia, and ATP is released via an unknown mechanism, which propagates ATP signaling
to adjacent cells. Cortex glia may also regulate synaptic transmission by uptake of glutamate
from the synaptic cleft via membrane transporters (green arrow) or the release of glutamate
upon reversal of the transporter induced by elevated intracellular Na+ (the red arrow)

References and Further Reading:

http://faculty.washington.edu/chudler/glia.html

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1226318/

http://shahamlab.rockefeller.edu/pdf/CTDB_69_C_69003.pdf

http://www.neuro.uoregon.edu/doelab/pdfs/Spana,Doe-Neuron96.pdf

http://www.hindawi.com/journals/jnd/2013/234572/fig1/

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