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Developmental Biology – Biology 4361 The Anatomical Tradition 2009 A hen is only an egg’s way of making a new egg. Samuel Butler,, 1885 The Anatomical Tradition - Overview What is developmental biology? How do biologists study it? Fundamental concepts and questions General questions Scientific approaches Historical Modern Core concepts Fundamental Questions & Concepts How does a fertilized egg give rise to the adult body? How does the adult body produce yet another body? Gametes Life Cycle Adult Fundamental Questions & Concepts Gametes Life Cycle Adult gametes 1 cell (haploid) 2 cell types zygote 1 cell (diploid) 1 cell type embryo multiple cells multiple cell types adult ~10 1011 cells 200+ cell types General Questions (according to Gilbert) 1 cell (1 type) creates ~1014 cells (~214 types) Yet, each cell in the zygote, embryo, and adult has identical DNA. 1. How do cells differentiate? General Questions: Differentiated cells are organized into complex sets of tissues with a variety of functions. 2. How are cells organized into tissues and organs? General Questions: During development, all cells, tissues, and organs naturally limit their growth. e.g. homeostasis… h t i each h cellll d duplication li ti mustt b be matched t h d by elimination of another cell - “perfect waste management and recycling”1 Pathological conditions often tip this balance - stroke/infarction - AIDS - cancers 3. How do cells know when to stop dividing? 1. Galluzzi et al., 2007 Cell Death and Differentiation 14:1237-1266 General Questions: Sperm and eggs are haploid and have many other cellular modifications that are necessary for reproduction reproduction. 4. How are gametes formed? General Questions: New phenotypes have the potential to be established only d i an organism’s during i ’ d developmental l t l period. i d 5. How do changes in development create new body forms? General Questions: During development organisms respond to the environmental conditions to which they are exposed. 6. How is development of an organism integrated into the larger context of its habitat? General Questions: 1. How do cells differentiate? [Differentiation] 2 How 2. H are cells ll organized i d into i t titissues and d organs? ? [Morphogenesis] 3. How do cells know when to stop dividing? [Growth] 4. How is g gametogenesis g accomplished? p [[Reproduction] p ] 5. How do changes in development create new body forms? [Evolution] 6. How is development of an organism integrated i t the into th larger l context t t off its it habitat? h bit t? [Environmental integration] Scientific Approaches Comparative p embryology y gy ((historic)) Experimental embryology (modern) Evolutionary embryology T t l Teratology Mathematical modeling g Comparative Embryology Dr. Nicole Valenzuela Richard N Feinberg, Greg Holmes Comparative Embryology Hippocrates (5th century BCE) - recognized development Aristotle (4th century BCE) - cleavage patterns patterns, viviparity, viviparity etc. etc * William Harvey (1640s) - Ex ovo omnia (“all from the egg”) Marcello Malpighi (1672) - microscopic account of development Origins – Preformation v. Epigenesis Preformation – new organism contained in sperm or egg - no cell theoryy (no ( size p problem)) - age of Earth unknown (so not a problem) - eliminated need for “vital force” Homunculus Epigenesis – new organism formed de novo (“from scratch”) epi - “after” genesis i - “origin” “ i i ” - explained mixture of traits in hybrids - explained l i d bl blending di off ttraits it - embryos had structures unknown in adults Comparative Embryology Hippocrates (5th century BCE) - recognized development Aristotle (4th century BCE) - cleavage patterns patterns, viviparity, viviparity etc. etc * William Harvey (1640s) - Ex ovo omnia (“all from the egg”) Marcello Malpighi (1672) - microscopic account of development Kaspar Friedrich Wolff (1733-1794) - differentiated tissues arise from undifferentiated cells Christian Pander (c. 1817) - germ layers, induction Germ Layers Germ layer – region of cells that give rise to all tissues and organs germ – initiates development or serves as an origin ecto- outside, external endod inside, i id iinternal, t l within ithi meso- middle, intermediate -derm d skin, ki covering i -blast immature form Germ Layers Diploblastic organisms (cnidaria, ctenophores, porifera) - 2 germ layers (lack true middle layer) Triploblastic organisms (vertebrates, echinoderms, etc) - 3 germ layers Germ Layers Diploblastic organisms (cnidaria, ctenophores, porifera) - 2 germ layers (lack true middle layer) Triploblastic organisms (vertebrates, echinoderms, etc) - 3 germ layers Ectoderm - outer layer; forms epidermis, brain, CNS middle layer; forms blood, heart, kidneys, Mesoderm gonads, bones, muscles, connective tissues inner layer; forms inside of digestive tract, Endoderm associated organs Triploblasts Diploblasts Comparative Embryology Hippocrates (5th century BCE) - recognized development Aristotle (4th century BCE) - cleavage patterns patterns, viviparity, viviparity etc. etc * William Harvey (1640s) - Ex ovo omnia (“all from the egg”) Marcello Malpighi (1672) - microscopic account of development Kaspar Friedrich Wolff (1733-1794) - differentiated tissues arise from undifferentiated cells Christian Pander (c. 1817) - germ layers, induction Karl Ernst von Baer (1820’s) - described blastula, notochord, mammalian egg von Baer’s Laws 1. General features of a large group of animals appear earlier in development than do the specialized features of a smaller group. 2. Less general characters develop from the more general, until finally the most specialized appear appear. 3. The embryos of a given species, instead of passing through the adult stages of lower animals animals, departs more and more from them. 4. Therefore, the early embryo of a higher animal is never like a lower animal, but only like its early embryo. von Baer’s B ’ work k marked k d th the ttransition iti ffrom mainly i l observational to experimental embryology. Scientific Approaches Comparative embryology (historic) Experimental embryology (modern techniques) Embryo manipulation Cell lineage Fate mapping Evolutionary embryology Teratology Mathematical modeling Experimental Embryology Techniques Isolation – remove and grow part of embryo by itself (no communication, signals, regulation from outside) Removal – a portion of the embryo is removed Wh t happens What h t the to th remaining i i embryo? b ? Is there a gap? Are organs or tissues missing? Transplantation – portion removed, transplanted to another embryo homospecific - same species heterospecific - different species h t heterochronic h i - different diff t age heterotopic - different place (same embryo) Tracing Cell Lineage C. elegans g invariant cell lineages - 959 cells; each lineage known Constructing Fate Maps zygote yg 8-cell Fate Mapping Fate Mapping Techniques Heterospecific transplantation Scientific Approaches Comparative p embryology y gy ((historic)) Experimental embryology (modern) Evolutionary embryology Teratology Mathematical modeling g Evolutionary Embryology Homologous structures? Analogous structures? Homologous Structures Evolutionary Embryology jointed legs etc legs, etc. barnacle larvae barnacle (arthropod) sea squirt larvae sea squirt (chordate) notochord, nerve cord Evolutionary Developmental Biology Peripatus Distal-less gene Scientific Approaches Comparative p embryology y gy ((historic)) Experimental embryology (modern) Evolutionary embryology Teratology/medical embryology Mathematical modeling g Medical Embryology & Teratology Mathematical Embryology Mathematical Embryology Mort Henick