Lecture 1 - Intro + Neural Development Flashcards
How much of the overall bodily energy does the brain use?
20% - a selfish organ
(liver will even break itself down to give the brain energy)
Can we tell what exactly every neuron in the nervous system can do?
with the exception of the retina - no we cannot
How many total human genes are in the genome? How many are ubiquitous? How many are only in the brain and how many are not expressed in the brain?
Total - 20,000 genes
Brain - 6,000 genes
Ubiquitous - 8,000 genes
Not in brain - 6,000 genes
What are the ionic concentration of the sea (high sodium, low potassium and high calcium) similar to?
our blood or ecf
Where did calcium come from in our blood?
limestone deposits brought calcium into the sea
Why is calcium concentration low in our cells?
-calcium in the cell is cytotoxic because it can form precipitates with phosphates and that is why nature made us have low conc. and exploits this to make calcium a secondary messenger
What is the soma of a neuron?
cell body or control center
What is the dendrite of a neuron?
signal input
What is the axon of a neuron?
specialized for long range electrical trasnfer
What is the synapse of a neuron?
output - transfer elec info into chemical and back into elec
What are some of the key experimental organisms and techniques used in molecular neuroscience?
model systems - drosophilia, worms, rodents
genetics - drosophilia
-development - frog xenpus oocyte and chick embryo because they are very malleable
What are the developmental axes?
the rostral-caudal axis
What are the three germ layers and at what stage of development are we at when they are present?
ectoderm, mesoderm, endoderm
-later than a blastocyst 5-10 days after conception
What does the ectoderm form?
forms the nervous system, exoskeleton, skin, CNS and PNS
What does the mesoderm form?
develops into organs and muscles, connective tissue and vascular system
What does the endoderm form?
the inner lining or organs; such as the digestive tract from the mouth to the anus; lung, pancreas, liver
What are the three primary model systems in development and why?
-chick embryos - have a three week development cycle so can take the embryo out manipulate it and put in
-xenopus frog oocyte - cheap, translucent and easy to manipulate
-mice (later in genetics)
In human development when do you have the nervous system?
-within a month
Humans and flies look similar in what stages of development?
in the earlier stages (up to stage 18 or 19) and then they diverge
When does nervous system development occur in mice and humans?
mice - the first and second week
humans - first and second month
At one month in a human or 2 weeks in a mouse what two flexures are present and what do they become?
-cephalic flexure - forebrain, midbrain, and part of the hindbrain
-cervical flexure - remaining hindbrain and psinal cord
If you stain for a ubiquitous nervous system gene where will you see regionalization occur?
in the ectoderm
What are the key events that underlie morphogenesis of the nervous system early in development?
-the regionalization of the neural tube
What does the ectoderm give rise to and what is it a precursor of?
neural plate - precursor of the CNS and PNS
What does the neural plate do to form the neural groove?
invaginate
What does the neural plate once it has invaginated to form the neural groove do to form the neural tube?
-buckles at its midline to form the neural tube
What folds close to form the neural tube?
the dorsal neural folds
What does the neural tube lie over and what does it do?
the notochord - forms the vertebral column or bones of spinal cord -send Shh signals to differentiate dorsal versus ventral neurons
What is the neural tube flanked by?
somites - they are mesodermal cells which give ruse to muscle and cartilage - send signals to differentiate anterior and posterior
What gives rise to three vesicles in the neural tube and when do you see this in mice?
-differences in the rate of cell proliferation
-one week in mice
What are the three vesicles the neural tube gives rise to?
-proencephalon - forebrain
-mesencephlon - midbrain
-rhombencephalon - hindbrain
At what stage in mice does the three vesicle neural tube give rise to five vesicles?
2 weeks in mice
What does the forebrain become during the five vesicle stage?
diencephalon and telencephalon
What does the midbrain become during the five vesicle stage?
remains as the mesencephalon or midbrain
What does the hindbrain become during the five vesicle stage?
metencephalon (pons and cerebellum)
myelencephalon (medulla)
What drives the progressive patterning and subdivision of cells and tissues in the brain?
many secreted molecules; every cell is drive to become something by default - how do you interrupt the default program and cause it to become something else
-the default is female but signals secrete to become male
What is the yin and yang of life or biology and how do you interrupt it?
all biological processes are programmed by default to do or become something
-can inhibit an activator or inhibit and inhibitor
What is the organizer region?
-plays an instructive role early in differentiation
-dorsal ectoderm; causes nervous system differentiation
If you take from a donor embryo of a frog xenopus oocyte and organizer region from the dorsal ectoderm what will happen to the receiving transplanted embryo?
two neural tubes will be developed so the organizer region is important in playing a role of the early nervous system organization
What are ectodermal cells supposed to be if there is nothing present?
neural tissue
If BMP is secreted from the ventral mesoderm then what to ectodermal cells become?
epidermal cells or skin cells
If BMP inhibitors are being secreted from the organizer region or dorsal ectoderm what do the ectodermal cells become even if BMP is being secreted from the ventral mesoderm?
neurons again
What are BMPs or bone morphogenetic proteins?
BMPs: group of growth factors and they play key role in morphogenetic signaling
-secreted proteins that are secreted out of cells and they signal active properties to other cell
-the first cells that were cloned were found to induce bond formation and a mutation that lead to constitutively active BMP lead random cells to be constantly instructed to become bone
What is mediated by peptide growth factors (BMPs) and their inhibitors (follistatin, chordin, nogin)?
neurons
What is the organizer region generating?
BMP inhibitors
What do ventral mesodermal cells and the ectoderm secrete?
BMP
What do the cells become in the presence of BMP?
skin cells
What do the cells become in the presence of BMP inhibitors or no BMP?
neurons
What is the default program of all ectodermal cells?
neurons
If BMP is present what do ectodermal cells become?
skin cells
If BMP inhibitors are present what do the cells become?
neurons
What turns on the secretion of BMPs from part of the ectoderm and ventral mesoderm?
Transcription factors
How do BMP inhibitors work and what are some examples of them?
they are secreted from the organizer region of the dorsal ectoderm and bind to BMP and block the ability of ectodermal cells to become skin
-chordin, noggin, follistatin
What promotes epidermal cell fate?
BMPs
If you take the ectoderm that is not the organizing region and leave those cells in a petri dish what do they become?
skin cells
If you take the ectoderm that is not the organizing region and leave those cells in a petri dish what do they become then add BMP inhibitors what do they become?
neurons
If you dissociate the cells what do they become and why?
neurons because the BMP concentration is not high enough when they are not close together to make them skin cells
