The paper, Pain
Most recent blogposts:
Most recent blogposts:
Part 14: Side trip out to the periphery! Part 14b: Prevention of pain neurotags is WAY easier than cure Part 14c: PW Nathan was an interesting pain researcher
SEE ALL PREVIOUS BLOGPOSTS IN THIS SERIES LISTED AT THE END
Foggy island resting spot
As promised, a brief interlude to deepen understanding information about glia and such.
Brain glia are not from neural crest
I found out something important (important to me, at least, because I sustained a mild case of cognitive dissonance-itis over it...) yesterday as I dug through books and papers. I used to think astroglia and oligodendrocytes, etc., in the brain, came from neural crest, because, when you look at a list of neural crest derivatives, you see the word "glia."
For example, from Bhatt et al,
"Cranial NCCs differentiate primarily into bone, cartilage, and connective tissues, but they also generate neurons and glia. In contrast, trunk NCCs give rise primarily to sensory neurons and glia that are central to formation of the peripheral nervous system."
My bold, which is what my confirmation bias had picked up on, ran with for years, and why I subsequently found myself confused.
It turns out brain glia (e.g., astrocytes) don't come from neural crest, they come from neuroectoderm. It might not seem like that big a deal, but it's important to me, because it means they likely are less related to neural crest than teeth are. It means that teeth and face bones and throat cartilage and brain meninges are probably more related to the peripheral sensory afferent and autonomic efferent nervous system than central nervous system glia are. Presuming cellular relatedness matters. So I stand corrected.
According to Kessaris et al (full access),
"All the neurons and glial cells of the central nervous system are generated from the neuroepithelial cells in the walls of the embryonic neural tube, the ‘embryonic neural stem cells’. The stem cells seem to be equivalent to the so-called ‘radial glial cells’, which for many years had been regarded as a specialized type of glial cell. These radial cells generate different classes of neurons in a position-dependent manner. They then switch to producing glial cells (oligodendrocytes and astrocytes). It is not known what drives the neuron–glial switch, although downregulation of pro-neural basic helix–loop–helix transcription factors is one important step. This drives the stem cells from a neurogenic towards a gliogenic mode. The stem cells then choose between developing as oligodendrocytes or astrocytes, of which there might be intrinsically different subclasses. This review focuses on the different extracellular signals and intracellular responses that influence glial generation and the choice between oligodendrocyte and astrocyte fates."
Nicoletta Kessaris, Nigel Pringle, William D Richardson; Specification of CNS glia from neural stem cells in the embryonic neuroepithelium. Phil. Trans. R. Soc. B 12 January 2008 vol. 363 no. 1489 71-85
|From Facebook, today.|
All the other books and papers I cracked yesterday said the same thing. Once that neural tube closes, that's it. Anything cranial that is tagged "neural crest" mostly ends up as meninges or bone or teeth or cartilage in the throat. Some of it gets into the brain, but doesn't turn into glia; it contributes to ganglia for certain (sensory) cranial nerves.
See more references at the end of the blogpost.
Wave after wave
Anyway, here's the cool way it all unfolds, according to Bhatt et al..
"During normal mammalian embryogenesis, neural crest cell induction and delamination begin at the level of the midbrain and continue as a wave that extends progressively caudal toward the tail."
"Waves" of neural crest cells detach and travel toward targets attracted by morphogens which set up irresistible chemo-gradients. Remember Peggy Mason? Here is what she says about morphogens (in a teeny sidebar):
"Morphogens are substances that spread by diffusion from a localized source and govern the embryological development and patterning of organs and body parts. Their effects depend on their concentrations - often so that high and low concentrations exert opposite effects. Among several morphogens involved in the patterning of the human nervous system, the protein sonic hedgehog plays an important role at very early stages. For example sonic hedgehog is expressed by the notochord when the dorsal-ventral differentiation of the neural tube begins. It also acts at later stages to guide axonal growth, attracting outgrowing axons in low concentrations, and repelling them in high concentrations (as shown for retinal ganglion cell axons growing from the eye toward the brain)."
There are scads more of those, and scads of info about them, but we need to move along, pick up where we left off - I choose to pick up the story of astrocytes, because of all the very very cool research recently on those particular glia, and how they might be connected to pain. So, next post will be about astrocytes.