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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Drosophila. . . . Drosophila

Poor little fruit fly

Lives a mere fourteen days unless

I choose thee to kill

(A Haiku by me on Drosophila melanogaster)

So here we are, blogging again even those I hoped to never have to actually us this page for academic purposes again, but as life would have it, Here I am again.

So the model organism I have chosen is Drosophila melanogaster.

What type  of cell am I?

I am a sensory neuron (or afferent neuron) and I belong to the peripheral nervous system of my organism. I am an important cell type for the survival of the fruit fly (whatever that means to the organism, I mean, how do they view time? Is it as seen in the movie Epic where humans are seen as large slow bumbling fools? How long does this few week life span actually seem to them? Ah, I digress; this is what stems from watching too much Doctor Who. I apologise).

So, a sensory neuron like any other cell of this organism starts life as a humble undifferentiated cell found in the embryo. This embryo undergoes roughly 13 cell divisions before things start getting complicated. The syncytial blastoderm is the insect embryo. This holds all the replicate nuclei in a single common cytoplasm before cleavage and specialisation.It is from this that the sensory neuron develops..

We begin our specialisation at stage 13, and we quickly develop our receptors and accessory cells that allow us to detect stimuli. By the end of stage 17 of embryonic development, we are fully formed and the embryo now proceeds to the development of the rest of the larval body.

Sensory neurons are bipolar ( has two extensions) or multipolar (meaning that they have many dendrites to associate with sensory organs but still have just one axon).  The cell body which houses the nucleus and all other organelles is found to middle of the sensory neuron.

 

Sensory neurons can be bipolar or multipolar

 

There are 15 sensory neurons that are multidendritic and are classed as dendritic arborization (da) neurons. The are classed from I-V based on the size of their receptive fields and complexity at the mature larval stage. Five of the six da neurons found in a particular segment of adult Drosophila were found to be those that persisted from the larval stage.

The sensory neurons of Drosophila m. are associated with the sense organs and the receptors and carry information to the CNS. These receptors can be found in the thorax where  six pairs of thoracic ganglia (a ganglion is a dense cluster of connected neurons that process sensory information and motor responses) control the leg and wing movement. Sensory neuron’s associated with the abdominal muscles help with control of those muscles while those found on the insects back end help with the control of the fly’s genitalia and anus.

FBim0000091

The 13th cell cycle when the sensory neurons start to differentiate

FBim0000114

After the 17th cell cycle, the sensory neurons are fully developed

 

The various ganglia that the sensory rectors and thus the sensory neurons are associated with.

 

More in-depth formation of the peripheral nervous system

References and Further reading:

http://flybase.org/.bin/fbimage?FBdv:00005289|FBbt:00000137

http://groups.molbiosci.northwestern.edu/holmgren/Glossary/Definitions/Def-S/syncytial_blastoderm.html

http://www.sdbonline.org/fly/atlas/12-13pns.htm

https://dgrc.cgb.indiana.edu/cells/store/catalog.html

http://honorsbiologyp6.wikispaces.com/P6+Insects+Sensory+Systems

http://www.cals.ncsu.edu/course/ent425/tutorial/nerves.html

http://www.neuraldevelopment.com/content/4/1/37

http://www.ivy-rose.co.uk/HumanBody/Nerves/Neurons.php

 

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Model Organisms

What is a model organism?

These are organisms on whom much data is already collected and thus their biological processes can be easily described. They are also simple in structure and features.

Used in research because:

1. They are readily available

2. develop rapidly and have short life spans/cycles

3. have a small (physical) adult size (housing them is made easier)

4. easy to manage groups of them.

Used in teaching because:

1. studying many problems in specific organisms is convenient

2.  scientific concepts are more easily visualized by students in using a model

3. these organisms can respon quickly to changes in the environment

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Namárië (Farewell)

I think this is my farewell post. I was going to do more, but it’s late and I’m tired. I really wanted to do one on the workings of Joker Venom, but that required a lot of reading. However, I take comfort in knowing that Joker venom is feasible and clearly, Joker was a bit of a Biochemist (albeit a crazy one).

This blog was an experience. Forced us to be creative ( I think I did rather poorly in that area), helped to revise what was done in class, made us research more and learn more, so this blog was a wonderful idea. Most of us may not get the full 10% but I think we’ll take anything above 6%

So farewell, for now wordpress. If I decide to blog via this site again, it will be using a new page. 🙂

To all the Biochemians:

Alámenë

Nai anár caluva tiellanna

Go with a blessing

And may the sun shine on your path

 

Now, the Doctor is calling

 

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Nucleic Acids

Nucleic acid wordle

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Biochemistry of the T-Virus

So the Hokage said to make our blog “pop”. So yes, I am very serious when I say I’m gonna do the Biochem of the T-virus (or as much of it as I possibly can)

This will be short though, since it has more to do with genetics, but I’ll try to relate it to Biochemistry as much as possible.

The T-virus, known to all us gamers and movie fans as the cause of the zombie epidemic in the Resident Evil series, works like any other virus; i.e. it invades the host’s cells, destroys them when they are done replicating and then starts the process all over again.

The virus however, also destroys the mitochondria and uses a replica of itself to produce energy.

Bad move T-virus. We know that the majority of our ATP is produced by the Electron Transport Chain in the mitochondria and without it, you’re just gonna get 2ATP from glycolysis(which takes place in the cytosol), and that’s not nearly enough to power the brain and all the basic bodily functions. Thus the living subject loses all higher brain function, leaving just the cerebellum working which allows for (rather poor) movement. The hormones of the hypothalamus are also not regulated and floods the blood stream leading to rage and hunger.

This also explains why zombies still bleed. The virus doesn’t target erythrocytes because they have no organelles to allow them to reproduce, and they also have no mitochondria to destroy since they get all their energy from glycolysis which is kept going due to the production of lactate which regenerates the NAD+ needed.

In other words, if the Umbrella Cooperation had engineered the virus to leave the mitochondria alone, they might have made a very powerful viral weapon, and could have possibly made more controllable subjects.

 

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Effects of Rotenone and Cyanide on the ETC

The Electron Transport Chain

 

Rotenone and Cyanide are both inhibitors of the ETC that prevent the production of the proton mtive force (PMF) that allows for the formation of ATP from ADP and an inorganic Phosphate group.

Cyanide binds to the Iron(III) in the Heme group of the Cytochrom oxidase C which is associated with Complex IV. The binding of cyanie prevents the oxidation reaction from taking place so no energy is released to allow the Complex to pump the Hydrogen ions out. Thus, the PMF does not build up and there is not enough energy to allow the H ions to return via ATP synthase and be coupled to the formation of ATP.

Rotenone works in a similar manner but affects Complex I instead.

Rotenone prevents the use of NAH as a substrate so oxidation of the NADH to NAD+ does not take place. No oxidation = no energy to pump the H ions into the intermembrane space leading to a weak PMF that does is not enough to drive the H+ back into the matrix and be coupled to ATP formation.

 

Therefore, to answer the question posed to us in the tutorial:

Cyanide affects Complex IV

Rotenone affects Complex I

And they both result in your death in high enough doses
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