BIO 127 study gude STUDY GUIDE FOR EXAM III I. Stem Cells and Ectoderm Neural Crest and Axons. The Big Picture: Location, Location, Location! => Stem Niches - Where you are located along with what signals you receive will dictate what you will become. A. What is a Stem Cell? Niches? Why are they important? 1. Roles a.) Involved in development of germ layers and inducing organogenesis. b.) Response to replenishing sources or injury/stress. 2. Types a) Mesenchyme: Degree of differentiation plasticity. Found in niches of both embyo and adults. b.)Adult stem cells are committed with limited potential. c.) Embryonic- formation of trophoblast or inner cell mass for ex. 3. Microenvironments a.) Differentiate and move on or stay the same and hang back? b.) Paracrine signals + cell interactions (ie: delta notch) 4. How stem cells divide in Drosophila – Cadherins holding on to 1st centrosome close to hub. 5. Too little or too much is bad. Aging and cancers/diseases. Help with concept of differentiation: “Living with the parents” concept – do you change and move out based on the house rules (signals) received. Or be obedient follow the signals and stay the same. - Change arises from being kicked out of the house B. Neurulation/Neurons 1. Define: Neurulation, Competence, Specification, Determination, Differentiation. How are they different? 2. Structure-Process-Structure 3. 1st Organ system developed- CNS (verts) Who's controlling? a.) 2 Major Steps i. Neural Tube Formation -Primary= folding of neural plate into tube directly. -Secondary= Mesenchymal Coalescence followed by 1 BIO 127 study gude hollowing out into a tube. ii. Neuron DIfferentiation 4. Location and type of signaling. a.) What to become? i. Primary Mechanism = Inhibition ii. Signaling from BMP and Wnt at different aspects of ectoderm determine structures. 5. Neural Tube a.) Primary and Secondary Neurulation. i. Hindge at Neural plate. -What happens when fail to close? Results: Spina Bifida, anencephaly, or cranioachischisis - Folate Supplements decrease defect rates (folate binding protein in neural fold during closure) ii. Coalescence of the Neural tubes b.) Differentiation of Neural Tube. i. What is occurring at gross, tissue, cellular levels - Early brain development Forebrain: Telencephalon, Diencephalon Midbrain: Mesencephalon Hindbrain: Metencephalon, Myelencephalon -All resultant of bulges and constrictions ii. Brain size resultant of osmotic Na+ gradient into ventricle -Stretching leads to increase neuronal division -Like filling a water balloon. Volume increase as well as neurons iii. Axes Development: What dictates? Location. Gradient. - Hox, TGF-Beta,, Shh A to P : Hox D to V: BMP and Shh 6. Differentiation of Neurons in the Brain. a.) a layer of stem cells give rise to Neuroepithelium that further gives rise to Ependymal, Neurons, & Glia cells. b.) Neuron i. Structure: growth cone, axons, and dendrites -synaptic partners. Myelination= incr. Speed. No ion exchange c.) Neural stem cell- formation of germinal epithelium i. Neuron Birthdays ii. Formation of the spinal cord d.) Differentiation of Cerebellum & Cerebral Cortex i. Cerebellum → coordinates phys./ motor function ii. Neocortex & 6 layers = complex reasoning iii. Neuron migration mechanism 7. Formation of Sensory System 2 BIO 127 study gude a). Cranial placode competency i. Olfactory ii. Eye 1. Optic cup, Delta Notch signal, Homeobox 2. Crystallin: from lens; terminal differentiation peptide 3. Expression of Retinal Homeobox - failure for expression = no occular material 4. Differentiation, Iris formation 5. Stem cells in the Eye (2): -Epithelial cells in front of lens and Neural crest cells of the cornea. 6. SHH: too little? too much? -cyclopism or eyeless. iii. Reciprocal induction 8. Epidermis and Cutaneous Appendages a.) Ectoderm forms Neural tube, Neural Crest, Epidermis b.) What is the Epidermis? What is included? c.) Layers i. Inner vs. Outer layers: Basal Lamina vs. daughters 1. Do you have contact with Notch? ii. Daughter cells migrate towards the surface Iii. Keratinocytes → Cornified Keratinocytes -dies to protect; “taking one for the team” iv. Basal Cells 1. express delta (jagged) while distal sisters (notch) - keratinocyte differentiation v. Reciprocal Induction for Hair Follicles- Mechanism 1. Dermal Fibroblasts → Dermal Papilla Dermal Papilla → Hair shaft, sebocytes, root sheath -Evagination by epidermis forms hair shaft 2. Hair = Keratinocytes + Melanin 3. Bulge= Stem cell niche for melanocytes - Supplies: sebaceous gland, dermal papilla, or epidermis - Stem cell migration mechanism -laser surgery = destroy bulge 4. Wnt + Dickkopf – placode controls spacing II. Neural Crest + Axonal Specification A. Neural Crest Fates 1. Neural Migration a) Neural crest cells can migrate from dorsal to lateral, to ventral. b.) Where you start out SPECIFIES your fate choices. The 3 BIO 127 study gude further down the road pathway, the signals received down that path more DETERMINED to a cell type. Help with Specificity/Determination Concept Ie: Making sandwich. All start out with bread and meat-specifies your fate choice, the sandwich. Choice of ingredients (Signals) during sandwich making process determines if you become a Italian sandwich(Pepperoni/Tomatoes) or Greek (Feta/Olives) sandwich. c.) Cell is dependent on the pathway and the signals it receives → dictates fate. d.) Cardiac Neural Crest i. CNS derived cardiac cells are resistant to atherosclerosis ii. Neural crest cardiac cells will Invade, destroy, and replace mesodermal derived cardiac cells. e.) Trunk Neural Crest i. Can migrate two directions: Dorsal & Ventral Pathway ii. Lateral & Ventral becomes Sympathetic ganglia, adrenal medulla, Schwann cells, etc. (Diversity) iii. Ventrolateral cell migration thru Anterior Sclerotome 1. somites dictate Ventral Lateral crest 2. Anterior Posterior Periodicity in Neural Crest Dorsal → ephrin → - Neural Crest→ migrate Anterior 3. Ephrin gene in posterior part of somites. Repelling biochemistry. f.) Vagal-Sacral- Parasympathetic neurons of the gut i. Migrating: Cell bodies (PNS) set up ganglia out in the tissue (distant). Cell bodies (CNS) are in spinal column. g.) Plasticity Experiment: Quail neural crest replaced with duck neural crest = quail with duck beak. i. Pre-determined cells will force surrounding cells to adopt fate. ie: pharyngeal endoderm implant = 2 beaks B. Neuronal Specification and Axonal Specificity 1. Induction and patterning of brain region 2. Birth and migration of neurons and glia 3. Specification of cell fates a.) combination of signals received further determines your cell type. b.) birthday + Vit. A determines pathway: column terni, medial, or lateral motor columns. Concentration of Retinoic acid (Vit. A) 4 BIO 127 study gude i. Each one requires appropriate signal as you traverse + position and time of birth. 4. Guidance of axons to specific targets a.) cells toward a specific pathway are signal specific. One signal will have affinity to attract a cell, while another will repel. This will ensure cells will follow the right pathway to become hamstring vs. quadriceps. b.) muscle like neurons must make the correct synapsis or die. i. Target + molecule = guide toward position ii. Without correct neuron synapsis at muscle, neuron dies as well as muscle. c.)Ephrins and semaphorins can cause the growth cone to collapse d.) Chemoattractants secretion signals/guides axon towards target site. Ie: Netrin & BMP 5. Formation of synaptic connections a.) Reciprocal Induction: Synaptic connection develops postsynaptic junction- induce clustering of Acetylcholine receptors i. Requires synaptic transmission 6. Competitive rearrangement of synapses a.) First induction creates competition for final innervation. i. Myelination follows. 7. Survival and final differentiation by signal. a.) Apoptosis is dominant influence. >50% neurons die b.) Neurotrophic factors block default apoptosis c.) Disease i. Huntington’s' Corea – loss of protein – brain-derived neurotrophic factor that allows survival of striatum neurons. ii. Parkinson’s – death of dopaminergic neurons for glialderived neurotrophic factor and conserved dopamine neurotrophic factor. 8. Continued plasticity throughout life a.) Can alter synaptic connections throughout life but decrease with age. 5