ORGANOGENESIS Organs and Organogenesis - General 1. Uniqueness a. Origin - germ layer(s) b. Position c. Structure d. Function 2. Organ primordia form from a specific germ layer (sometimes layers), usually in the region of the body where the organ will be located. 3. Differentiation ===> Histogenesis ===> Function Organogenesis - general 4. Organogenesis involves a. inductions b. migration of cells in some instances c. shape change (at both cellular and tissue levels) d. changes in cellular gene activity differentiation/histogenesis e. growth - organ size, cell number f. in some cases, cell death 5. All these factors work in concert to “mold” the primordium into a functional organ. ORGANOGENESIS - ECTODERM P. 234, Carlson Neurulation (human embryo) http://courses.temple.edu/neuroanatomy/lab/embryo/ntube.htm Neural Crest Cells 1. Multipotent cells that arise from the edges of the forming neural plate 2. Migrate throughout body to form many different tissues/structures. 3. Two paths of migration a. Dorsolateral (superficial pathway) b. Ventral (deep pathway, between and through the somites) http://www.erin.utoronto.ca/~w3bio380/lecture16.htm Neural Crest Cells 4. Neural crest cells from cranial region form: a. Sensory components of cranial nerves V, IX, X b. Schwann cells c. Contribute to branchial cartilages d. Contribute to membranous bones of skull e. Dentin of teeth f. Contribute to head mesenchyme g. Cranial parasympathetic ganglia h. Ciliary muscles of eye http://www.nlm.nih.gov/medlineplus/ency/imagepages/19080.htm i. Meninges of CNS (dura mater, arachnoid, pia mater) http://vanat.cvm.umn.edu/neurHistAtls/pages/men1.html Neural Crest Cells 5. Neural crest cells from truck region form: a. Parasympathetic and sympathetic ganglia b. Dorsal root ganglia c. Meninges of CNS (dura mater, arachnoid, pia mater) d. Schwann cells e. Adrenal medulla 6. How can they become so many different things? 7. Multiple inductions along their paths of migration. Neural crest cell migration in the chick hindbrain. Neural crest cells leave from near the midbrain (m), midbrain/hindbrain boundary (m/h) and rostral rhombomeres (r1 and r2) and spread out to cover a wide region adjacent to the neural tube. Duration: 7 hrs Time interval between images: 3 min http://authors.library.caltech.edu/12902/ https://embryology.med.unsw.edu.au/embryology/index.php/Chicken_Neural_Crest_Migration_Movie_1 Cranial Nerves & Ganglia Mnemonic “On Old Olympus’ Towering Top A Finn And German Vault And Hop” Olfactory (I) Optic (II) Oculomotor (III) Trochlear(IV) Trigeminal (V) Abducens (VI), Facial (VII) Acoustic (VIII) Glossopharyngeal (IX) Vagus (X) Accessory (spinal accessory) (XI) Hypoglossal (XII) Cranial Nerves & Ganglia vestibulo-acoustic petrosal (distal) Froriep’s ganglion is temporary group of nerve cells associated with the hypoglossal nerve (CN XII) of the embryo. It does not persist into the adult stage. Origin of the Cranial Ganglia Origin of the Cranial Ganglia Neural crest contribute sensory neurons to the ganglia of CN V, IX, and X Neural crest Dorsolateral placode The dorsolateral placodes contribute to the “special” sense organs (olfactory, optic (lens), otic). Epibranchial placode Contribute sensory neurons to the ganglia of cranial nerves V, VII, IX and X. Know the cranial ganglia, their origins, and the nerves they are associated with. geniculate superior (proximal) neural crest (superior) & petrosal (distal) & epibranchial placode (petrosal) jugular (proximal) & nodose (distal) Froiep’s ganglion Froriep’s The Neural Tube (primordium of the CNS) Shape change of cells as the neural plate forms P. 236, Carlson Central nervous system development Shape change in cells P. 239, Carlson Central nervous system development http://courses.temple.edu/neuroanatomy/lab/embryo/histo.htm Later cell division in the neural tube Establishes cells the ependymal, mantle and layers marginal Establishes the ependymal, mantle and marginal layers Outside Establishment of ependymal, mantle and marginal layers in spinal cord Similar to P. 439, Carlson PATHFINDING BY AXONS A. General neuron structure Myelination In CNS - oligodendrocytes In PNS - Schwann cells B. Neurons and synapses Mauthner neuron Initiates tail-flick escape response by activating groups of motor neurons in the spinal cord. Hibbard, 1965 - pathfinding by axons in amphibian and fish hindbrain (medulla). Anterior Anterior Posterior Posterior Hibbard, 1965 - pathfinding by axons in amphibian and fish hindbrain (medulla). Anterior Anterior Posterior Posterior Hibbard, 1965 - pathfinding by axons in amphibian and fish hindbrain (medulla). REVERSED ORIENTATION Anterior Anterior Posterior Posterior Anterior Anterior Posterior Posterior Mechanisms for axon pathfinding 1. 2. Stereotropism (contact guidance) a. Singer et al., 1979 - stereotropic pathfinding in neuroepithelial matrix of a newt embryo (amphibian) b. Silver and Sidman, 1980 - stereotropic pathfinding in mouse retina Differential adhesion (integrins, cadherins) a. Letoureau, 1975 - diff. Adhesive pathfinding in vitro. 3. Galvanotropism a. Patel et al., 1984 - pathfinding along charge differential pathways in vitro. 4. Chemotropism (netrin, connectin, nerve growth factor) a. Gunderson & Barrett, 1979, 1980 - pathfinding in response to chemical signals in vitro. Axon Pathfinding - chemotropism http://web.sfn.org/content/Publications/BrainBriefings/ axon.html#fullsize Blue - attractant molecules Orange - repellent molecules “Axons locate their target tissues by using chemical attractants (blue) and repellants (orange)” Either diffusable substances released by cells or molecules embedded in the plasmalemma Surfaces of target tissue cells can also display attractant or repellent molecules. Illustration by Lydia Kibiuk, Copyright © 1995 Lydia Kibiuk. The Growth Cone http://journal.frontiersin.org/article/10.3389/fnana.2011.00062/full The growth cone Axons that extend from the retina to the tectum of the midbrain. http://www.anat.cam.ac.uk/pages/staff/academic/holt/images.html Optic chiasma As growth cones reach a point in axon growth where a decision must be made, they change shape and speed of growth and become more active. Filopodia appear to be searching for the right signal. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=0mVzBEg1E X_YMkzpc2FN_TNTHWJTpj89DoajBTA4 (Optic chiasma) (Optic chiasma) One possible signal at the optic chiasma is a glycoprotein called CD44. If CD44 is not expressed or if the cells that express it are eliminated, the growing axons from the sensory retina ganglion cells do not cross the chiasma. http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=0mVzBEg1EX_YMkzpc2FN_TNTHWJTpj89DoajBTA 4 Examples of the effect of molecular signals on growth cone progress - Research by David Sretavan M.D., Ph.D., Doctor of Opthalmology University of California, San Francisco Growth of retinal axons in mice in response to specific retinal proteins Eph (Ephrin) type proteins - can modulate axon pathfinding. Have attractive, repulsive and other effects on axon growth. “The following QuickTime movies show retinal axon growth cones responding to gradients of Eph type proteins. Videos presented at 420 times normal axon growth rate.” i.e., 1.5 min = about 10 hr http://ucsfeye.net/dsretavanresearch.shtml The human brain By the sixth prenatal month, nearly all of the billions of neurons (nerve cells) that populate the mature brain have been created, with new neurons having been generated at an average rate of more than 250,000 per minute. http://www.futureofchildren.org/information2827/information_show.htm?doc_id=79339 The human brain At birth - 100 billion neurons in brain = 100,000,000,000 1000 billion glial cells = 1,000,000,000,000 However, the wiring of the brain is not yet complete at birth. As a baby starts to experience life, connections are made between neurons - the more connections there are, the more the brain can do. Much of the brain’s growth after birth is due to the development of numerous dendrites that receive synaptic connections from growing axons. A baby's brain develops so fast that by age two a child who is developing normally has the same number of connections as an adult. By age three, a child has TWICE as many brain connections as an adult. http://www.preschoolrainbow.org/brain-growth.htm Adult - an average of 10,000 synapses per cortical neuron Very rough estimate, 10,000 synapses/neuron X 100,000,000,000 neurons = 1,000,000,000,000,000 synapses = 1000 trillion synapses in the adult brain How big is 1000 trillion? There is nowhere near enough information in your DNA to code for the specific locations of all these synapses. Much of this “wiring” is completed after birth and results from the child’s interactions with his/her environment. Developing coordination By age three, a child has TWICE as many brain connections as an adult = 2000 trillion Use it or lose it! Synaptic connections are winnowed as children grow. Those not used are lost while those that are used are retained. (Neurotrophic factors produced by the cell that grew the axon are necessary to maintain the synapse). The more you do something, the better you get (e.g., practice improves your hand-eye coordination). Practice makes perfect. This is true for young children and also, to a certain extent, when you get older (however, a child’s brain has much more “plasticity”). Does this apply to other aspects of nervous development? Influence of Inheritance and Environment on ability Environmentally determined outcome Virtuoso Totally incompetent Genetically set limits WHY IS THIS IMPORTANT? BECAUSE YOU WANT YOUR CHILDREN TO BE ALL THAT THEY CAN BE!!!!! Inductions in the peripheral nervous system Inductions in the peripheral nervous system Olfactory epithelium 1. Formation of olfactory placode a. Induction #1 - presumptive head endoderm b. Induction #2 - presumptive head mesoderm c. Induction #3 - telencephalon - seals fate 2. Cells of olfactory epithelium form stem cells, neurons and supportive cells 3. Olfactory neurons extend axons to regions in the developing telencephalon that will form the olfactory lobes. 4. Pathfinding by axons 5. Synapse on other neurons in olfactory lobes 6. Neurons in the olfactory epithelium have a life-span of about 1 month 7. Must be replaced from stem cells 8. Axons are constantly extending from these new neurons into the olfactory lobes where new synapses are formed. Inductions in the peripheral nervous system Otic vesicle/inner ear 1.Induction #1 - Chordamesoderm passes near presumptive otic placode tissue 2. Induction #2 - nearby paraxial (somitomere) mesoderm further conditions cells 3. Induction #3 - Lateral wall of myelencephalon seals fate and causes placode to form and invaginate - forming the otic vesicle Utricle - semi-circular canals, utriculus Saccule - cochlea, sacculus DEVELOPMENT OF THE EYE Lens placode Lens placode Human - 7 - 8 wks Choroid fissure choroid fissure Human ~ 10 wks opticoel posterior chamber iridica (muscles) vitreous body pars iridica ciliary body (muscles) lens ligament opticoel optic stalk (optic nerve) ora serrata pars caeca retinae pars ciliaris pars iridica (iris) pars optica retinae pigmented retina sensory retina vitreous body Development of the Human Retina neuroblastic iridica (muscles) Development of the Human Retina neuroblastic neuroblastic Development of the Human Retina neuron neuroblastic Development of the Human Retina neuron ganglion cells (neurons) Innermost neuron layer Outer neuroblastic layer Inner neuroblastic layer lens the lens added