5 th ANNUAL SINAUER ASSOCIATES DISTINGUISHED SCIENTIST LECTURE James W. Truman, Ph.D. Howard Hughes Medical Institute Chevy Chase, Maryland Neuronal Lineages in the CNS of Drosophila: Units of Development, Behavior, and Evolution 4 :00 PM Friday, October 15 th Electrical Engineering Lab 2 Lecture Hall (room 119) Mast Cell Mast Cells! Basophilic granules in cytoplasm! Mast cell Fc receptors bind circulating IgE antibodies (2)! Antigens bind to IgE (3)! Mast cells degraulate, releasing granule contents (3)!Anaphylactic shock 1
PLASMA CELLS Appearance - Large, ovoid, considerable cytoplasm - Basophilic, abundant RER - Nucleus: spherical, eccentric, clockface pattern of heterochromatin Function! Antibody synthesis & secretion Plasma cells Adipose cells! Function! Fat production and storage *** Unilocular (White) Adipose Multilocular (Brown) Adipose Development of Adipose cells 2
Adipose cells Unilocular: White Adipose -fat storage -scant ring of cytoplasm signet ring -single large lipid droplet -flattened, eccentric nuclei Adipose cells Multilocular: Brown Adipose -mitochondria -heat production -newborns, small mammals -polygonal -much cytoplasm -multiple lipid droplets size varies -round nuclei~ central Brown Fat: multilocular adipose cells Composition!Cells!Fibers CONNECTIVE TISSUE!Ground substance Extracellular Matrix (ECM) Categorized by:! Ratio of cells/fibers/ground substance! Specific molecular components 3
Loose Connective Tissue! Location:! Fill spaces between fibers and muscle cells! Ensheath blood and lymphatic vessels! Beneath epithelia! Composition:! Abundant Ground substance! Few fibers! Fibroblasts and macrophages Loose Connective tissue Dense Connective Tissue! Location:! Tendons! Composition:! Ground substance! Abundant fibers- Type I Collagen! Fibroblasts and macrophages! Types:! Regular! Irregular 4
Regular Dense Connective Tissue Irregular Dense connective tissue Elastic Tissue! Location:! Aorta, arteries, mesentery, skin! Composition: -Elastic Fibers -Weigert's stain for elastic fibers lumen Reticular Connective Tissue! Location:!Bone marrow!lymphatic organs!forms loose meshwork for support of cells! Composition:!Enriched in reticular fibers!type III Collagen 5
Reticular Connective Tissue Cartilage! Specialized form of connective tissue! Function:!Mechanical stress!shock absorber!sliding area of joints!template for development of long bones Composition of Cartilage Extracellular Matrix proteoglycans hyaluronate Type II collagen (also Types IX, X, XI) ECM traps water-->resists compression Cells! Chondroblasts-young, from perichondrium! Chondrocytes-more mature, in lacuna 6
Hyaline cartilage Types of Cartilage! Fetal skeleton (Epiphyseal plate)! Larynx, trachea, bronchi Perichondrium Fibroblasts Chondroblasts ECM: CollagenType II, GAGs, Proteoglycans Lacunae Isogenous group Chondrocytes Territorial matrix Interterritorial matrix Terms used to describe hyaline cartilage Adipose Tissue Growing Hyaline Cartilage 7
Chondrocytes Synovial Joint: No perichondrium at articular cartilage - located in lacunae -! avascular -! no innervation - nourished by: - perichondrium - synovial fluid Chondrocytes!Lacunae (spaces) contain 1---> several chondrocytes Isogenous Groups!Territorial matrix!rich in sulfated proteoglycans!interterritorial Matrix!More lightly stained!reduced sulfated proteoglycans 8
Cartilage growth!interstitial!division of pre-existing chondrocytes: isogenous groups!appositional!differentiation of new chondrocytes from perichondrium Adipose Tissue Growing Hyaline Cartilage 9
Perichondrium Appositional Isogenous groups Interstitial 5-bromo-2-deoxyuridine (BrdU) is incorporated into the DNA (nuclei) of dividing cells. Cells that were dividing when BrdU was injected can be identified using an antibody that recognizes BrdU. You inject BrdU into developing mice. You take a sample of developing hyaline cartilage from mice 1 day and 14 days after BrdU injection. Inject BrdU 1 14 TIME Samples at day 1 and 14 Predict the pattern of BrdU labeling in both the 1 day and 14 day sample. Illustrating your predicted results in a drawing of cartilage. Cartilage Remodeling Normally: Dynamic remodeling of cartilage But the Volume of cartilage is maintained. Balance degradative enzymes / synthetic enzymes Degradative enzymes: matrix metalloproteinases secreted by synovial cells & chondrocytes a) collagenases b) stromelysins c) gelatinases. 10
Regulation of Matrix Metalloproteinase (MMP) Activity -secreted as proenzymes- must be activated -plasma and tissue inhibitors of MMPs Arthritis! Osteoarthritis: degeneration of articular cartilage due to excessive activity of MMPs! Rheumatoid arthritis: autoimmune disease! Damage of synovial membrane and articular cartilage Repair of Cartilage -Limited capacity for repair -No blood supply -Best repair if damage is to perichondrium -Articular cartilage at high risk autologous cultured chondrocytes Genzyme Corporation, Cambridge, MA Types of Cartilage!Hyaline cartilage!fetal skeleton (Epiphyseal plate)!larynx, trachea, bronchi!elastic cartilage!ear!larynx!fibrocartilage!between dense connective tissue and hyaline cartilage!attachment of some ligaments to bone 11
Elastic Cartilage: Elastic fibers and Type II collagen; ear, epiglottis Fibrocartilage: Collagen Types I and II; intervertebral disc, pelvis, mandibular joint, knee, shoulder The Meniscus: Fibrocartilage Normal knee anatomy The ends of your femur (thigh bone) and tibia (shin bone) are covered with articular cartilage. This slippery substance helps your knee bones glide smoothly across each other as you bend or straighten your leg. Two wedge-shaped pieces of meniscal cartilage act as "shock absorbers" between your thighbone and shinbone. Different from articular cartilage, the meniscus is tough and rubbery to help cushion and stabilize the joint. Each knee has two menisci, one on each side of the joint. Articular Cartilage is hyaline cartilage found at joints. http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/9621.jpg&imgrefurl=http://www.nlm.nih.gov/medlineplus/ency/imagepages/9621.htm&usg= czpggnmutmh_- kdb4xfufe3poca=&h=320&w=400&sz=16&hl=en&start=3&um=1&tbnid=zlyax8lp4dvuum:&tbnh=99&tbnw=124&prev=/images%3fq%3dmeniscus%2bnih%26hl%3den%26um%3d1 12
Bone Function:!Mechanical support!protection!reservoir of calcium and phosphate!locomotion!hearing Composition of Bone ECM: becomes mineralized---> BONE -90% Collagen-mainly Type I, some Type V -Ground Substance -GAGs, glycoproteins CELLS: - Osteoprogenitor cells! Osteoblasts! Osteocytes! Osteoclasts!Hematopoiesis Bone Tissue Compact (dense): dense layer on outside of bone Spongy (cancellous): meshwork of trabeculae (spicules of bone), spaces filled with blood vessels and bone marrow 13
Bone Classification!Long bones 1 longer dimension tibia, metacarpels!short bones!flat bones Bone Classification!Long bones!short bones Length=diameter Carpal bones of hand!flat bones Bone Classification!Long bones!short bones!flat bones Thin, plate-like skull and sternum Bone Classification! Long bones! Short bones! Flat bones! Irregular bones Other shapes vertebrae 14
Periosteum: covers outer bone surface Exception: where bones meet, ---> articular cartilage Endosteum: covers inner bone surface One cell layer--> osteoprogenitor cells Inner layer of periosteum - osteoprogenitor cells Outer fibrous layer Lamellar Bone -cylindrical units Haversian system or Osteon -center: Haversian Canal -Lamellae -concentric -interstitial -circumferential -!Volkman s Canals perpendicular blood & nerve supply 15
Osteon Mature (Lamellar) Bone rings of osteocytes Mature (Lamellar) Bone Volkmann s and Haversian Canals 16