Differentiation of Neurons and Glial Cells Flashcards
Past Review* What is the process of Grastrulation?
Embryo transforms from blastula (single layer of cells) to germ layers (ectoderm, mesoderm, and endoderm)
Past Review* What is the process Neurulation?
Cells within ectoderm form the neural plate which happens depending on the formation of the notochord (Mesoderm)
Past Review* What does the Neural Plate form?
Floorplate, roofplate, and neural crest
Past Review* What happens after Neural Tube formation?
Mesoderm forms somites, acting as precursors of axial musculature and skeleton
Past Review* What populates the Neural tube?
Multipotent neural precursor cells and radial cells
Inductive Signals* What is Retinoic acid (RA) and where does it come from?
- lipophilic / drives cellular different ion of neural stem cells, neuronal pattering and axonal growth in early embryogenesis
- released by roofplate, notochord, floorplate
- RA binds to retinoids receptors, interacting with transcription co-factors that modulates gene expression
Inductive Signals* What does neural tube malformation cause?
Vitamin A (metabolic precursor of RA) in excess or deficiency can cause birth defects
Inductive Signals* What are the superfamilies of peptide hormones?
- Fibroblast Growth Factors (FGF) —> 23 ligands
- bone morphogenetic proteins (BMPs) —> 6 ligands
- Transforming Growth Factors (TGIβ)
Inductive Signals* What is the role of FGFs?
FGFs are secreted into extra cellular matrix, binding to receptor tyrosine kinases, activating raw-MAP kinase pathway
- FGF8 —> forebrain and hindbrain development, inducing gene expression
Inductive Signals* What is the role of BMPs?
BMPs are released by roofplate for bone development and differentiation of dorsal spinal cord, hindbrain, and cerebral cortex. Also plays a role in induction of neural ectoderm
- If BMPs are expressed, cells will form the epidermis; If BMP is blocked by noggin/chordin (endogenous antagonists), will form neuroectoderm
Inductive Signals* What is the role of Wnts in the Canonical Pathway?
Wnts (19 ligands) act on 2 distinct pathways;
Canonical Pathway:
- activation of Frizzled receptor and stabilization of β-catenin, translocating to nucleus and interacts with transcription factors inducing gene expression
Inductive Signals* What is the role of Wnts in the Non-Canonical Pathway?
Non-Canonical Pathway:
- regulates cell movement (migration) and fate to lengthening of plate/tube from interaction with Frizzled, changes to intracellular Ca2+ and Protein kinase c
- can lead to the activation of JUN kinase (JNK), regulating cell shape and polarity
Inductive Signals* What is the role of Sonic Hedgehog (Shh)?
- Acts on patched and smoothed surface receptors to translocate Gil1 and/or Gil2 into nucleus
- If no Shh, inhibition occurs and only Gil3 is active to repress expression of target genes
- Shh is important for differentiation of neurons within ventral spinal cord (motor neurons)
Inductive Signals* What is the role of signals working together?
- Create gradients of effects to regulate neural tube formation and differentiation during different phase
- Specifically, signals in the spinal cord can act to induce or inhibit gene expression by direct and indirect signalling —> expressing different levels of gene expression
Stem Cells* What is a Stem cell and its purpose?
- a stem cell is an example of manipulating the change in identity of a cell, specifically from Blastocyst, to become any other cell
Shinya Yamanaka:
- discovered mature cells can be reprogrammed into Induced Pluripotent Stem (iPS) cells
- 3/4 factors in fibroblasts (Oct3/4, Sox2, Klf4) can create iPS cells
Inductive Signals* What is the role and process of Delta and Notch?
- Must be neighbouring cells —> Delta: transmembrane ligands, Notch; surface receptors
- Once bound, notch Intracellular domain (NICD) is cleaved, translocating to the nucleus, which is then binding to transcription factors that induce expression of neural fate (basic helix-loop-helix (bHLH))
- Delta-Notch signalling can lead to downregulation of Delta in some cells and upregulation in others
- Relative Notch and bHLH regulate the generation of glial cells (oligodendrocytes and astrocytes) —> balance of factors
Inductive Signal* What is the step by step process of Inductive signals forming cells
- Neural Induction: where ectoderm forms into neuroectoderm through the act of Noggin/chordin blocking BMPs
- Organizer Centers: where neuroectoderm form into neural tube
- Neural patterning: where activation of TGF-βs forms the roof plate and where activation of Shh horns the floor plate
- Neurogenesis; where activation of bHLH genes and inactivation of Notch forms neuronal precursors, which form into neurons
- Oligodendrogenesis:
Where activation of Olig1/2 and Nixon2.1and the inactivation of Proneural bHLHs, which forms oligodendrocytes precursors, leading to forming oligodendrocytes - Astrogliogenesis:
- Epidermiya
Inductive Signals* What are Macroglia cells derived from and regulated by?
Macroglia (astrocytes and oligodendrocytes) derived from neural progenitors (radial glial cells) —> regulated by inductive factors and gene expression following neurogenesis
Inductive Signals* What is something to remember about Differentiation of factors?
- same precursor can lead to differentiation of factors but at different times of development
- gradients of inductive signals determine dorsal - ventral / rostrum - caudal neural differentiation
- these gradients help to understand that the time point can be different and these factors involved can be doing different things
Inductive Signals* Discuss the importance and process of a Migratory Path.
- migratory path of cells helps to regulate final position and identity of postmiotic cells
- migratory path of neural crest cells are first influenced by anterior (rostral) - posterior (caudal) position in neural tube
Inductive Signals* Describe the migratory pathway for Neural Crest cells (NCCs).
- NCCs start as neuroectodermal cells, undergoing an epithelial to migratory transition
- NCCs upregulate Snail 1 and 2 to inhibit protein expression and cellular adhesion
- NCCs are attracted in the periphery (mesodermal layer) by somites
- NCCs follow distinct paths to help distinguish finial position and identity
Inductive Signals* What are the neuronal population that are specialized?
Unipolar sensory neurons —> dorsal root ganglia of peripheral nervous system
Chromaffin cells —> adrenal medulla of the adrenal gland
Autonomic neurons —> cranial nerves, sympathetic chain, and autonomic ganglia
Inductive Signals* What is considered the “small brain”?
Neural crest —> enteric nervous system —> regulating gut motility, digestion, and immune function
- disrupts migration of NCCs —> digestive syndromes (Hirshprung’s disease)
