All courses · elective
Developmental Neuroscience
An elective that follows Cell Signaling. It starts with a sheet of embryonic cells and ends with a working, wired brain: how tissue becomes neural, how neurons are made and move, how axons find their targets, why half the neurons die, and how experience refines what the genes began.
11 units · 51 lessons
Unit 1 · The problem and the tools
- Unit 1: The problem and the tools The Wiring Problem: How a Brain Gets Built About 20,000 genes, about 86 billion neurons. How does the smaller number wire the larger one?
- Unit 1: The problem and the tools Seeing Neurons: Golgi, Cajal and the Neuron Doctrine Two men looked at the same stained brain and saw two different organs. Who was right, and how could anyone tell?
- Unit 1: The problem and the tools Harrison's Living Axon and the Growth Cone In 1907 a scrap of frog embryo in a drop of lymph settled how a nerve fibre is made.
- Unit 1: The problem and the tools Tools for Following Cells and Genes A neuron has no label saying when it was born or where it came from. So how do you find out?
Unit 2 · Becoming neural
- Unit 2: Becoming neural The Organizer: Spemann and Mangold How can a small graft make its host build a second spinal cord from cells meant for skin?
- Unit 2: Becoming neural Neural Induction: The Default Model Pull a square of frog skin-to-be apart into single cells, and it becomes neural. Why?
- Unit 2: Becoming neural Neurulation and Neural Tube Defects In a human embryo the neural tube has closed by the end of about the fourth week after fertilization. What happens if it doesn't close?
Unit 3 · Coordinates: patterning the tube
- Unit 3: Coordinates: patterning the tube Head to Tail: Hox Genes, Retinoic Acid and Rhombomeres How does a vitamin A drug taken for acne reach the part of an embryo that builds the face?
- Unit 3: Coordinates: patterning the tube Local Organizers: The Midbrain-Hindbrain Boundary How does one protein on a bead make a second midbrain grow, built back to front?
- Unit 3: Coordinates: patterning the tube Ventral to Dorsal: Sonic Hedgehog and BMP in the Neural Tube Graft a second notochord beside a chick neural tube, and the tube grows a second floor.
- Unit 3: Coordinates: patterning the tube Transcription Factor Codes: Building a Motor Neuron Two transcription factors, two cell types: swap one partner and the same protein builds an interneuron instead.
- Unit 3: Coordinates: patterning the tube Mapping the Cortex: Areas and Arealization Add one secreted protein to the back of a mouse embryo's cortex and a second whisker map can appear there.
Unit 4 · Making neurons
- Unit 4: Making neurons The Ventricular Zone: Radial Glia as Stem Cells Why does a progenitor copy its DNA in one place and divide in another?
- Unit 4: Making neurons Proneural Genes and Lateral Inhibition Every cell in the cluster could become the neuron. Why does only one?
- Unit 4: Making neurons Asymmetric Division: Numb and the Neuroblast How does one cell divide into two sisters that are different from the moment they are born?
- Unit 4: Making neurons Birth Order and Fate: Temporal Identity and the Inside-Out Cortex In the mouse cortex, the first neurons born end up deepest. Why do the latecomers climb past them?
Unit 5 · Cells on the move
- Unit 5: Cells on the move Radial Migration: Climbing the Glial Ladder A newborn neuron can keep reaching forward while its nucleus stays behind. What pulls the nucleus?
- Unit 5: Cells on the move Reelin and the Reeler Mouse Why does a mouse that cannot walk straight have its cortex built in the wrong order?
- Unit 5: Cells on the move Tangential Migration: Interneurons and the Long Way Round In a mouse embryo, most of the neurons that will inhibit the cortex are born outside it.
- Unit 5: Cells on the move The Neural Crest: Cells That Leave Home Why can one mutation leave a child with a nerveless colon, a white forelock and deafness?
Unit 6 · Axons find their way
- Unit 6: Axons find their way One Axon, Many Dendrites: Neuronal Polarity Cut a neuron's axon close to the cell body and one of its dendrites can become a new axon.
- Unit 6: Axons find their way Pioneers, Guideposts and the Logic of Guidance Cues Kill a guidepost cell on a grasshopper embryo's leg, and the first axons to grow past it lose their way.
- Unit 6: Axons find their way Netrin and DCC: One Cue, Two Answers The same protein pulls one axon toward the midline and pushes another away. What decides?
- Unit 6: Axons find their way Crossing the Midline Once: Slit, Robo and Comm An axon is pulled toward the midline, crosses it, and then treats it as forbidden ground. What changed?
- Unit 6: Axons find their way Semaphorins and Repulsion A protein that makes growth cones fold up and stop at about ten picomolar: what is it for?
- Unit 6: Axons find their way Topographic Maps: Sperry's Eye and Eph Gradients Turn a newt's eye upside down, let the nerve regrow, and it turns its head down toward a lure held above it. Why does it not learn?
- Unit 6: Axons find their way Choosing a Partner: Layers, Self-Avoidance and Smell A fly gene can make 38,016 different proteins. Why would one neuron need its own face?
Unit 7 · Survival and competition
- Unit 7: Survival and competition Too Many Neurons: Naturally Occurring Cell Death A chick embryo makes about 20,000 motor neurons for its legs, and about 40% of them die within a week. Why?
- Unit 7: Survival and competition The Neurotrophic Hypothesis Tested Neutralize one protein in a newborn mouse and its sympathetic ganglia waste away. Does that protein decide how many neurons there are?
- Unit 7: Survival and competition Neurotrophins, Trk Receptors and p75 How can one growth factor keep one neuron alive and kill another?
- Unit 7: Survival and competition The Death Machinery in Neurons Stop a starving neuron from making new proteins, and it lives longer. Why?
- Unit 7: Survival and competition Competition: How a Target Picks Its Neurons If the target makes too little NGF for every neuron, which neurons get to live?
- Unit 7: Survival and competition The Signal from the Target Travels Home A neuron hears its survival signal at the far end of its axon. How does the message get home?
- Unit 7: Survival and competition Pruning Without Dying: Axons That Cut Themselves Back How does a neuron cut off a whole axon branch with the same enzymes that could kill it?
Unit 8 · Building synapses
- Unit 8: Building synapses Building the Neuromuscular Junction: Agrin, Lrp4 and MuSK A mouse without the muscle kinase MuSK dies at birth: its motor axons reach the muscle, but no junction forms.
- Unit 8: Building synapses Synapses in the Brain: Adhesion, Scaffolds and Astrocytes A kidney cell that makes one neuronal protein can persuade an axon to build a nerve terminal on it.
- Unit 8: Building synapses Synapse Elimination: One Muscle Fiber, One Axon A newborn rat muscle fiber has two or more motor axons on one synapse. Where do the extra ones go?
Unit 9 · Experience refines the wiring
- Unit 9: Experience refines the wiring Activity Before Experience: Spontaneous Retinal Waves Weeks before vision begins, the retina already fires in waves. What are they for?
- Unit 9: Experience refines the wiring Ocular Dominance and the Critical Period Why does closing one eye of a kitten for a week rewire its cortex, when closing both eyes does much less?
- Unit 9: Experience refines the wiring Opening and Closing a Critical Period A mouse that lacks one enzyme for making GABA keeps its critical period waiting for months. One drug starts it.
- Unit 9: Experience refines the wiring Microglia and Complement Prune Synapses Why would a developing neuron make the first protein of an immune cascade that marks bacteria for destruction?
- Unit 9: Experience refines the wiring Sensitive Periods in Behavior: Song, Language and Sight A young songbird that never hears an adult sing grows up singing a simple, abnormal song. Why can't it catch up later?
Unit 10 · Glia
- Unit 10: Glia Where Glia Come From The brain's own immune cells were born outside the embryo, in the yolk sac.
- Unit 10: Glia Myelination: Wrapping the Axon A mouse called shiverer has all its nerve cells. What makes it tremble is one missing protein in the wrapping.
- Unit 10: Glia Feeding the Axon: Glia as Metabolic Partners The brain is about 2 percent of your weight and uses about 20 percent of your resting energy. Who delivers the fuel to the far end of an axon?
Unit 11 · Rebuilding, evolving, and going wrong
- Unit 11: Rebuilding, evolving, and going wrong Injury and Regeneration: Why the Brain Does Not Regrow Cut a mouse nerve and the stump falls apart in about a day. In one strain of mouse it lasts for weeks. Why?
- Unit 11: Rebuilding, evolving, and going wrong New Neurons in the Adult Brain Your cortical neurons are as old as you are. How do we know, and is the hippocampus different?
- Unit 11: Rebuilding, evolving, and going wrong When Building Goes Wrong: Microcephaly, Zika and Lissencephaly Why does the same doublecortin mutation give a boy a smooth brain and his mother a second band of cortex?
- Unit 11: Rebuilding, evolving, and going wrong Disorders of the Synapse: Fragile X, Rett Syndrome and Autism If a circuit was built without a protein, can switching the protein on in an adult undo the effects?
- Unit 11: Rebuilding, evolving, and going wrong What Makes the Human Brain Big Your cortex is only about twice as thick as a mouse's. Why is its surface roughly a thousand times larger?
- Unit 11: Rebuilding, evolving, and going wrong Brains in a Dish: Stem Cells and Organoids Can a few weeks in a spinning flask turn a person's skin cells into a model of their early cortex?