Reading NEUROSCIENCE: 5 th ed, pp. 477-506 NEUROSCIENCE: 4 th ed, pp. 545-575 Bio 3411 Wednesday 2 Summary from Lecture II Biology Understanding the brain is THE major question in biology and science. Is it possible for the brain to understand itself? The brain like any organ has functions: input, output, thought, communication. Brain Diseases Interfere with brain functions as heart disease interferes with the circulation. Many diseases have a strong genetic component. Prevalence is high: 15-30% of the population. Cost is high: >> $2+ Trillion/year in care, lost income, social services, etc., in the US. Impact (personal, family, societal) is persistent, pervasive, enormous, incalculable. 3 4 Issues for thought Neurons (=nerve cells) 100 Billion [the number of stars in our galaxy the Milky Way!!] Synapses (=clasp) 1/1,000,000 th of all stars & planets in the universe/person [less than the total of human synapses of people living in the St.L area!!] vs Genes 50% of 20,000-25,000 genes in the human genome are expressed only in Brain [70% of the balance are also expressed in the nervous system; the total is 85% of the genome] Developmental Neurobiology Major scientific challenge. To understand the normal construction and operation of the embryonic (and adult) nervous system. To understand human neuronal diseases, and possible ways to repair and renew the nervous system. To understand neuronal plasticity, and learning and memory. To understand the evolutionary diversification of nervous systems. 5 6 1
Major Questions 1. Origins: Where do neurons come from? 2. Identity: How does a cell become a neuron? Development proceeds by progressive developmental restrictions pluripotent, stem cell 3. Specificity: How does a neuron make the right connections? 4. Plasticity: Does experience modulate the above? differentiated 7 8 Developmental Restrictions may be: 1) Genetic (programmed by genes) or 2) Epigenetic (determined by environment) pluripotent, stem cell EGG Proliferate Constructing a Nervous System Sort genetic Shape Specify BRAIN environmental differentiated Axons & Synapses Cell Death & Life Experiences 9 10 Egg Blastula Germ bands and cell types. Body axes. Folding, involutions and morphogenic movements. Origin, migration and differentiation of neurons. Vertebrate (Frog) An oocyte contains positional information (cytoplasmic determinants) contributed maternally. Some maternal RNAs are not uniformly distributed throughout the egg. The first informational axis is intrinsic to oocyte! 11 12 2
Fertilization triggers an influx of calcium, that sweeps across the egg. This causes rapid release of cortical granules to form the fertilization envelope, blocking polyspermy. The point of entry of the sperm determines a second positional axis, ventral (entry point) and dorsal (opposite to entry point). Sperm entry point Sperm entry point Cortical granules Ca +2 Cortical Rotation mixes cytoplasmic determinants and creates the dorsal-ventral axis. Ventral Dorsal Gray Crescent (future blastopore) 13 future Nieuwkoop Center 14 Gray Crescent Formation in Xenopus Cortical Rotation redistributes maternal cytosolic determinants that are partitioned in different dividing embryonic cells Gray Crescent Courtesy of Jeffrey Hardin University of Wisconsin Nieuwkoop Center 15 16 Early Cell Divisions in Amphibians Generate a Blastula Fate Mapping the Blastula: 3 Major Spatial Axes Formed by Gradients of Signaling Molecules () blastomere blastocoel Blastula (Ventral) Site of sperm entry future (Dorsal) (Vegetal) 1. /Vegetal (Maternal Determinants) 2. Dorsal/Ventral (Sperm Entry, Cortical Rotation) 17 18 3
Bio 3411 Fate Mapping the Blastula: 3 Major Spatial Axes Formed by Gradients of Signaling Molecules; Nieuwkoop Center Induces the Spemann Organizer (Anterior) Fate Map of the Blastula: 3 Principle Germ Bands (Layers) Generated Ectoderm (Skin, Neurons) (Anterior) () (Posterior) (Posterior) (Ventral) Spemann Organizer (Dorsal) Mesoderm Nieuwkoop Center (Notocord, Muscle, Kidney, Bone, Blood) (Vegetal) 1. /Vegetal (Maternal Determinants) 2. Dorsal/Ventral (Sperm Entry, Cortical Rotation) Endoderm (Lining of Gut, Lungs, Placenta in Mammals) 3. Anterior/Posterior (Spemann Organizer) 19 Gastrulation of the Amphibian Blastula A & B: 20 Gastrulation of the Amphibian Blastula C & D: tissue origami by large-scale cellular migrations and morphogenesis 21 tissue origami by large-scale cellular migrations and morphogenesis 22 Gastrulation of Xenopus Blastula: 3-D Microscopic (Confocal) Reconstruction Gastrulation of the Amphibian Blastula E & F: tissue origami by large-scale cellular migrations and morphogenesis (Ewald, et al., 2004) 23 24 4
Gastrulation and neurulation in Xenopus (Courtesy of Jeffrey Hardin, University of Wisconsin) Endoderm and Mesoderm Involute with Gastrulation Mesoderm underlies (Neuro)Ectoderm, And induces the neural plate Neural plate (apposition of different germbands/ layers) and yolk plug 25 26 Early cell divisions in the Zebrafish embryo (Courtesy of Paul Myers, University of Minnesota) Neurulation Ant Closure of the neural tube. Post 27 28 Neurulation Origin of Floor Plate and Neural Crest Formation of Neural Crest Cells (makes PNS, endocrine cells, pigment cells, connective tissue). Neural Crest D V 29 30 5
Origin of Floor Plate and Neural Crest Cephalization and Segmentation of the Neural Tube Neural Crest 31 32 Cortical Development: Laminar structure of the cortex is constructed from the inside-out Labeling of Single Precusors Reveal Shared Clonal Origins of Radial Glia and Neurons; and Direct Visualization of Radial and Tangential Migrations Neurons are born in the ventricular layer and migrate radially along glia to their differentiated adult cortical layer. The earliest born neurons are found closest to the ventricular surface (thymidine pulse-chase labeling of dividing cells). (Rakic, 1974) (Cepko and Sanes Labs, 1991) (Nadarajah, et al., 2002) (Nector, et al., 2001) 33 34 The amount of yolk determines the symmetry of early cleavages and the shape of the blastula 1. Isolecithal eggs (protochordates, mammals): 2. Mesolecithal eggs (amphibians): Mammalian eggs have no yolk, so early divisions resemble isolecithal eggs (protochordate-like). However, later stages resemble the blastodisc of telolecithal eggs (reptile/bird/fish-like) (epiboly) 3. Telolecithal eggs (reptiles, birds, fish): a) Blastula flattens into the inner cell mass. b) Endodermal cells form the trophoblast and placental structures. (blastodisc) 35 36 6
What this Lecture was About 1. Three germbands (layers), ectoderm (skin and neurons), mesoderm (muscle, blood and internal organs) and endoderm (lining of the gut). 2. Development proceeds from pleuripotency (stem cells) to the differentiated state (adult neuron). 3. Neuronal induction requires specific contact between groups of cells; embryonic morphogenesis allows this to occur. 4. Positional information is created early by asymmetric distribution of molecules. These form axes (/Veg, D/V, Ant/Post) that guide the movement of embryonic cells. What this Lecture was About (cont): 5. Guideposts: a) Fertilization/Cortical Rotation. b) Blastula (hollow ball of cells). c) Gastrulation (inside-out involution of surface cells to the interior, through the blastopore). d) Neurulation (neural tube formation). e) Segmentation/Cephalization. f) Birth of neurons from the ventricular zone. Radial, then tangential migration to final destination. 37 38 Central Aspects of Embryogenesis 1. Oocyte possess maternal cytoplasmic determinants. 2. Fertilization triggers calcium influx, and creates dorsal-ventral axis by cortical rotation. 3. Cell divisions, synchronous at first, then asynchronous. 4. Blastula created. ( Hollow ball of cells) 6. Germ bands (ectoderm, mesoderm, endoderm) created by molecular signals along the /Vegetal axis. 5. Gastulation. (Involution of superficial cells through the blastopore). Embryogenesis (cont.): 7. Apposition of future mesoderm with neuroectoderm induces the neural plate. 8. Neurulation. (Lateral neural folds bend over the midline and fuse into the neural tube.) 9. Neural crest cells derived from leading edge of neural folds, migrate into somites to form the PNS. 10. Segmentation, anterior enlargement (cephalization), cortical development and spinal specification. 6. Anterior-posterior axis created by Spemann organizer. 39 40 END 7