Embryo 2nd lecture Flashcards
When and where does neurogenesis occur?
following formation of the neural tube. The process of cell proliferation in neurogenesis occurs in regions known as the VENTRICULAR ZONE that are the layer closest to the neural tube lumen/ventricles.
Describe the changes in nuclear position that occur during the cell cycle of neuronal precursors.
During S phase, nuclei are situated superficially. During M phase (mitosis), nuclei are situated most deep (adjacent to ventricle).
describe methods used to study neurogenesis
1) You label dividing cells with detectable DNA precursors (e.g. 3H-thymidine or bromodeoxyuridine). 2) C14 date (from nuclear testing) has also been used, since it has declined dramatically yet people were exposed to it.
what is meant by a neuron’s birthdate?
A cell’s birthdate is defined as the time it undergoes its last round of DNA synthesis (S phase).
Does a neuron’s birthdate influence its differentiation?
After it undergoes S phase, it divides. This is when it makes the decision to exit the cell cycle from M phase. If it does so, it is then considered a post-mitotic neuron and neuronal differentiation begins. Neurons born together end up in the same layer and follow similar programs of differentiation.
Which brain regions are areas of secondary neurogenesis?
1) external granule layer (EGL), which is impt for the development of granular neurons in our cerebellum postnatally. 2) subventricular zone (found near lateral ventricules, adjacent to ventricles), which give rise to olfactory bulb neurons. 3) dentate gyrus of hippocampus .
describe an asymmetric cell division
plane of cleavage of a progenitor cell influences whether daughter cells remain attached to the ventricular surface or whether they will differentiate. Perpendicular to ventricular surface = remain attached. Parallel to ventricular surface = one remains attached, and one does not and differentiates. 2 daughter cells are different, so its asymmetrical.
what factors/mechanisms determine when a cell stops dividing and begins differentiating?
1) plane of cleavage (determines inheritance of cytoplasmic proteins, mRNAs, other factors).
Where are the first-born cells found in the cerebral cortex with respect to the ventricular zone?
closer to the ventricular zone
where are first-born cells found in the retina with respect to the ventricular zone?
first-born cells (ganglion cells) are found farther from the ventricular zone.
Define preplate with respect to neuronal migration.
in the cerebral cortex, the first neurons to become postmitotic migrate a distance of several cell bodies and form a new region known as the preplate (forms at about 8-9 weeks of embryogenesis).
Define subplate with respect to neuronal migration.
A subdivision of the preplate that exists between the ventricular zone and the cortical plate. Importance –> these are among the earliest born neurons and play pioneering roles in circuit formation. They die and are thus transient.
What role do radial glia play in neuronal migration?
In the cerebral cortex — after a preplate is formed, radial glia are used as a guide during migration. This explains why cortical cells that serve similar functions are arranged in columns.
What are the 3 stages of neuronal migration in the cerebral cortex?
1) onset of migration 2) ongoing migration 3) migration stop
what genes play a role in neuronal migration in the cerebral cortex and which stages of migration do they affect?
onset of neuronal migration: filaminA (FLNA). migration process: LIS1, doublecortin (DCX). stopping migration: reeler, Dab1, Vldlr, and Apoer2.
Define radial, tangential and chain migration.
1) radial – use of radial glia. that mechanism. causes progeny of a single progenitor to be found in clusters. 2) tangential – neurons migrate from regions known as ganglionic eminences (medial, lateral, and caudal) upwards into cerebral cortex. **This causes cells from a single progenitor to be dispersed throughout a particular tissue. 3) chain migration – neuronal precursors move as chains in a pathway known as the rostral migratory stream. they migrate on top of each other.
What class of neurons undergoes radial, tangential, and chain migration, respectively?
radial migration accounts for majority of migration trajectories in the cerebral cortex, including glutamate containing neurons. tangential: inhibitory **GABA-containing cells in the cerebral cortex. chain migration = subventricular neurons that give rise to olfactory neurons.
What are neural crest cells?
These cells arise from the boundary region between the neurectoderm and epidermis. After neural tube closure, they constitute a mass of cell on top of the DORSAL tube.
What neuronal populations do neural crest cells give rise to?
peripheral nervous system, pigment cells, cartilage. derivatives of neural crest cells can be found in diverse locations, including the gut, skin, and sensory ganglia.
contrast migration of neural crest cells to radial migration in the cerebral cortex.
neural crest cells migrate really fast and don’t use cellular guides like radial glia. It’s their position along the rostro-caudal axis prior to migration that influences their fate. They follow 2 migratory paths in the trunk: dorsal stream and ventral stream. They are guided by permissive surface membrane proteins (laminin/fibronectin) and they express integrins which recognize surface membrane prtoeins. Other substrates are repulsive. When they reach their final destination, they express cadherins (adhesion molecules) and aggregate.
Compare and contrast apoptosis with necrosis.
1) necrosis: occurs in response to extreme changes in physiological conditions and leads to death via LOSS OF MEMBRANE INTEGRITY. Characterized by swelling of the ER and mitochondria. Associated with trauma and other external injury. 2) apoptosis: occurs under normal physiological conditions and the cell actively participates. cytoplasm and nucleus condenses and DNA fragments. cells are removed by phagocytosis, which protects neighboring cells. Predominant form of cell death in development.
Describe when cell death occurs in the nervous system. When is it most pronounced?
prenatally and postnatally. It is more pronounced for the neurons that are generated during adulthood, well after birth and the perinatal period.
What are neurotrophins?
several classes of molecules that promote cell survival. also regulate development and function in the CNS.
What role do neurotrophins play in neuronal development?
1) inhibit apoptotic cell death programs. 2) induce programs of differentiation required for process formation. they play a “permissive” role, ie. they allow cells to extend processes. 3) involved in synapse elimination 4) modify synaptic transmission (modulate efficacy and promote structural changes that later alter patterns of connectivity) 5) mediate some of the long-term consequences of conditions involving abnormal brain function.
Provide examples of long-range and short-range axon guidance molecules and identify which are attractive or repulsive.
LONG-RANGE (diffusible): netrins (attractive), semaphorins, netrins (repulsive). SHORT-RANGE (contact-dependent): cadherins, CAMs, (on cell surface) collagen/laminin/fibronectin/proteoglycans on ECM (attractive); semaphorins, ephrins (cell surface), teanscin (ECM): repulsive.
What factors influence the ability of axons to regenerate?.
1) ability of axons to grow 2) the presence of molecules that promote growth 3) the presence of molecules and receptors that inhibit growth (Nogo)
