12 Unicellular vs. Multicellular organisms Tranmembrane proteins (e.g C. elegans genes over yeast)-Ion channels-Cell adhesion molecules-Cell surface receptorsGene regulatory proteins(e.g. HLH gene family: 141 humans, 84 fly, 41 C. elegans, 7 in yeast)
13 How species can be different? Different animals utilize similar collection of genesSpecies identity genes (e. g 1% between human and chimpanchee )non-coding, regulatory DNA sequences are highly differential between species
14 Different genome causes different behaviors of cells UrchinUrchinFrogFly, MouseFrog8.5
21 How cell fate is determined? AutonomousspecificationRegulativespecification
22 Commitment Three modes of initiating commitment have been described. Autonomous SpecificationConditional SpecificationSyncytial Specification
23 Autonomous Specification = cell fate is determined before fertilization my morphogenetic determinants in ovum.Morphogenetic Determinants= mRNA or proteins that cause cellular commitmentMosaic Development= embryo functions like a “mosaic” of independent self-differentiating parts.
26 Mosaic DevelopmentdeterminantzygoteDies or 1/2 Embryo Forms
27 Conditional Specification Conditional Specification = cell fate is determined by the conditions surrounding the cell.Morphogenetic determinants produced by cells within the embryo. (signaling among cells)Regulative Development = cells of an embryo can change fate based on the conditions within the embryo.
28 Regulative Development Normal Embryo Formszygote
30 Syncytial Specification Syncytial Specification = cell fate is determined by the conditions affecting nuclei in a single multinucleate cell.Syncytium = a cytoplasm containing multiple nuclei.Morphogens may form a gradient within the cytoplasm.
31 Basic mechanisms of cell fate determination Inductive interactionMorphogenExtracellular inhibitorIntrinsic program for time courseLateral inhibition
32 Basic mechanisms of cell fate determination Inductive interactionMorphogenExtracellular inhibitorIntrinsic program for time course
33 Morphogen = Soluble molecule that causes cellular commitment but is secreted some distance from the target cells.Morphogen Gradient = concentration gradient of a morphogen.
37 Influence of Other Cells Morphogen Receptor Gradient = frequency gradient of the receptors for a morphogen in target cell cell membranes.Morphogen gradientMorphogen receptor gradient
38 Activin GradientActivin = morphogen in frog blastula, morphogen gradient of activin commits cells as a type of mesoderm.No activin = ectodermheartcellsnoto-chordmuscleblood
39 Frog Blastula (section) ectodermmesodermendodermblastocoelvegetal pole
40 Morphogenetic FieldMorphogenetic Field = a group of cells whose position and fate are specified with respect to the same set of boundaries.Within a morphogenetic field fate is not yet specified.The limb field will form a limb.If divided the limb field will form two limbs.
43 Basic mechanisms of cell differentiation Inductive interactionMorphogenExtracellular inhibitorIntrinsic program for time course
44 Basic mechanisms of cell differentiation Inductive interactionMorphogenExtracellular inhibitorIntrinsic program for time course-Time keeping mechanisms-Cell division associated-Glial progenitor cells become oligodendrocytes after 8 divisions
45 Morphogenesis Commitment Cell shape changes. Cell movement. Cell death.Changes in cell membranes or secreted products.
47 General Cell TypesEpithelial Cells = cells connected together in sheets (attached to each other and an acellular basal lamina).fold, elevate, expand, involute, intercalateMesenchymal Cells = cells unconnected together and operate independently.ingress, migrate
53 Cell AffinitySelective Affinity = Disassociated cells will group together with (positive affinity) or will not group together with (negative affinity) only certain other cells.Homotropic Aggregation = Disassociated cells of the same type group together. (positive afinity)
54 Cell AdhesionDifferential Adhesion Hypothesis = explains patterns of cell sorting based on thermodynamics of affinity between adhesion molecules.Surface tension.Different adhesion molecules.Different amounts of the same type of adhesion molecules.
55 2 different amounts of the same adhesion molecule Cell Affinity2 differentadhesion molecules2 different amounts of the same adhesion molecule
56 Cell Adhesiveness Adhesion molecules = proteins in cell membrane. Cadherins (5 classes)calcium dependent adhesion moleculesbinds to other cadherins (same type)connected to cytoskeleton by cateninsHomophilic binding = adhesion molecules attach to the same class of adhesion molecule.
59 Methods for developmental biology Descriptive embryologyExperimental embryologyDevelopmental genetics
60 Origins of Descriptive Embryology Epigenesis vs. Preformationismpreformationism argued for species continuity and constancyto some, epigenesis implied a need for a mysterious vital “life force” that was required to create life de novocareful observations on the anatomical development of embryos eventually required acceptance of epigenetic development
61 Classical EmbryologyKaspar Wolff (1767): studies of chick embryogenesisWhere did the instructions to build the embryo come from?Were they internal or external?‘vital force’ [vis essentialis] needed to explain embryonic organization?
62 Classical Embryology Christian Pander (1774-1865) studied the chick embryo and identified primary germ layers found in triploblastic embryosectoderm: gives rise to outer layer of embryo and nervous systemendoderm: gives rise to innermost layer and gives rise to digestive tube and associated organsmesoderm: middle layer that gives rise to bones, connective tissues, kidney, gonads, heart and hematopoietic systemprimary germ layers interact to form organs
63 Classical Embryology Karl Ernst Von Baer (1792-1896) “enwicklungsgeshicte”: extended Pander’s observations; discovered notochordhis work on chick embryogenesis was death knell to preformationism (also discovered mammalian egg)
64 Classical Embryology Von Baer’s laws: the general features of a large group of animals appear earlier in development than specialized features in a small groupwithin embryos, specialized structures develop from more generalized structuresan embryo does not “pass through” the adult stages observed in lower animals: ontogeny does not recapitulate phylogenyearly embryos share characteristics in common and become more and more divergent as development proceeds
65 Classical Embryology Wilhelm His (1831-1904) one of the major antagonists to Haeckeldeveloped the microtome, allowing for serial sectioning and much better anatomical resolution and reconstructionfocused on the the mechanics of development and the importance of morphogenic movements, foldings and cellular interactions in the process of development.
66 The birth of experimental embryology Defect = destroy part of embryo.Isolation = remove part of embryo and observe its development in culture.Recombination = replace part of an embryo with a part of the same embryo.Transplantation = replace part of an embryo with a part from a different embryo.
67 Birth of Experimental Embryology Laurent Chabry (1887) ‘Qualitative mosaic’experiments performed by isolating specific cells in developing tunicate embryoseach blastomere was responsible for producing a particular set of larval tissuesthe blastomeres were apparently developing autonomouslymosaic development: embryo constructed of individual modules capable of self-differentiation
68 Birth of Experimental Embryology Wilhelm Roux ( ) ‘Quantitative mosaic’student of Haeckel who performed ablation experiments in frogsResult of fate mapping in frogs implied that the destruction of certain regions in the early blastula would preclude development of certain structuresdestroyed right or left halves of frog embryos at 2 and 4 cell stagesobtained “half embryos” having a complete right or left side, arguing for a mosaic model of development
69 Birth of Experimental Embryology Hans Driesch ( ): ‘Regulative development’each of the blastomeres from a two cell embryo developed into a complete larvaesome of the later stage cells also developed into complete larvaeconflicts with experiments of Roux and Chabry: first example of regulative development
70 Birth of Experimental Embryology Hans Driesch ( ): pressure plate experiment; by compressing the developing embryo between two plates, he could force a change in cleavage plane from equatorial to meridional, resulting in a different pattern of cleavage from normal. This reshuffled the position of the nuclei in the embryo…did it alter the fate map?Embryos were normal
71 Birth of Experimental Embryology Pressure plate experiments implied:nuclear equivalencecytoplasmic/nuclear interactionsDriesch left science as a result of these experiments; he could not explain these results relative to the physics of his day and came to the philosophical view that living things can not be explained solely through physical laws
72 Experimental Design Matters! J. F. McClendon (1910) Repeated experiments in frog development using Driesch’s isolation technique relative to Roux’s ablation techniquenoted regulative development NOT mosaic developmentisolated frog blastomeres developed into a whole frogablated blastomeres were still in contact with intact blastomeres; they still were providing information for developmental programming
73 Fate MappngFate maps do not necessarily imply commitment; not maps of potency or states of determinationclonal restriction does not imply determination: allocation: clonal restriction in a population regardless of state of commitmentcommitment: intrinsic aspect of a cell that makes it follow a particular developmental path‘commitment’ vs. ‘determination’?
74 The birth of developmental genetics C. elegans, Drosophila, Frog, Mice, Plant as model systems