Using Fig. 7.92, design a problem to help other students better understand source-free RL circuits.
Lecture 30 Details of Development Overview 4 key stages to animal development: o Fertilization o Cleavage o Gastrulation o Organogenesis Mechanics of morphogenesis o Cell fates o Development of body axes o Limb development Fertilization Leads to Pregnancy and Temporary Disruption of the Cycles Fertilization (“conception”): sperm fuses with mature oocyte in oviduct o 24 hours: first cleavage (deuterostomes, radial) o 2-3 days zygote reaches uterus o 1 week: blastocyst (hollow ball of cells), implants in endometrium o Develops into fetus Embryo produces hGC (human chorionic gonadotropin) o Works like LH to keep corpus luteum from degrading o Keeps progesterone levels up o hGC can be detected in mother’s urine; pregnancy test Pregnancy: one or more embryos in the uterus Most Developmental Work is Done with Species Other Than Humans We must rely on model organisms o Fruit fly: Drosophila melanogaster o Sea urchin: various species, e.g., Strongylocentrotus purpuratus o Frog: Xenopus laevis o Chick: Gallus gallus o Nematode: Caenorhabditis elegans A good model organism is one that is: o Cheaply available or can breed in the lab o Has properties that make it useful for studying some biological process o From a species that we don’t mind killing Development of a Zygote Begins at Fertilization Fertilization: union of sperm and egg o N + N = 2n o Best studied in sea urchins; external fertilization Unfertilized egg o Plasma membrane with receptors o Vitelline layer: extracellular matric o Jelly coat: protects egg and attracts sperm Contact triggers acrosomal reaction o Acrosome: vesicle at sperm tip with hydrolytic enzymes break down jelly o Acrosomal process: structure with proteins that bind receptors on eggs Matching receptors ensures sperm matches egg o Fusion of plsma membrane o Depolarization: fusion leads to change in membrane potential Fast block to polyspermy Fertilization is a Process, Not an Event Fusion also initiates cortical reaction o Vesicles in cortex (outer part) fuse with plasma membrane o Contents (enzymes, etc.) lead to fertilization envelope and slow block to polyspermy Separate vitelline layer from plasma membrane Breaks up receptors Following cortical reaction, the egg is “activated” o Increased respiration & protein synthesis o Sperm nucleus fuses with egg nucleus o First cell division after 90 minutes Mammal fertilization basically the same, except: o Internal fertilization o No fast block to polyspermy o Egg completes meiosis II after fertilization o First cell division after 12-36 hours Cell Divide to Form a Blastula Cleavage: earliest divisions, rapid o Cells divide, but don’t grow o Blastomeres: individual, cells Blastula: hollow ball of cells with a blastocoel Relatively simple in sea urchins The Body’s Polarity is Established from the Beginning of Cleavage Development of body polarity is well-studied in frogs o Because parts of zygote are color-coded; easy to follow Even before fertilization, oocyte not just an unorganized blob o Cytoplasmic determinants: proteins, mRNA, etc. in various places o Yolk: stored nutrients Two poles that determine first divisions o Yolk concentrated toward the vegetal pole o Opposite: animal pole Some polarity set a fertilization o Animal vegetal axis anterior posterior axis o Area opposite sperm entry (gray crescent) dorsal Cortical rotation Presence of yolk influences shape of blastula o First 2 divisions, lead to 4 blastomeres o 3 division: 8 cells; unequal offset by yolk o Blastocoel only in animal hemisphere Gastrulation is the Process by Which Adult Germ Tissues Are Formed During gastrulation the ball of cells turns into a structure with 2-3 tissue layers and a gut (gastrula) o Mass movement of cells For a sea urchin, this is exactly the process we have already talked about o Three tissues (germ layers) are ectoderm, endoderm, and mesoderm o Starts at vegetal pole Migratory future-mesoderm cells enter blastocoel Other cells (future-endoderm) form vegetal plate Vegetal plate invaginates and becomes archenteron Opening is the blastopore: future-anus (deuterostome) Gastrulation is More Complex in a Frog Because of all the Yoke Slit-like blastopore forms on dorsal side; extends around entire blastula At same time, future-endoderm and – mesoderm expand by involution; shrinks blastocoel End of gastrulation, blastopore surrounds yolk plug All This is Slightly More Complicated in Birds by the Large Amount of Yolk In the chicken, disk of blastoderm forms as two layers of cells on a large yolk o Hypoblast on near yolk, epiblast on top Gastrulation by migration of epiblast cells toward yolk; forms primitive streak (- blastopore) o Future endoderm forms archenteron thru lateral folds pulling away from yolk Organogenesis as in frog, except for the presence of extraembryonic membranes o Chorion: gas exchange o Amnion: encloses embryo in fluid o Yolk sac: surrounds yolk o Allantois: sequesters waster produts o All formed of embryonic tissues Among Eutherian Mammals, Nourishment From the Yolk is Replaced With Nourishment From the Mother Because nourished by mother, eutherian eggs can be smaller: no need for bulky yolk o Rest of process similar to birds o Best studied in mice and early stages of human in vitro fertilization Cleavage to 8-blastomere stage: 3 days o After six days, ready to implant in uterus; > 100 cells 1. Blastocyst: mammalian blastula o Trophoblast: outer epithelium o Inner mass calls: part that will become the embryo 2. Trophoblast initiates implantation o Secretes enzymes to break down endometrium o Thickens, sends extensions to maternal blood vessels o Inner mass cells from epiblast and hypoblast 3. One implanted, gastrulation initiated & embryonic membranes form o Placenta derived from trophoblast, mesoderm from the epiblast, and endometrial tissue 4. Three layered embryo with 4 extraembryonic membranes The Human Gestational Period is Typically 38 Weeks First 2-3 weeks: embryo gets nutrients directly from endometrium Placenta forms from embryonic and material tissue; blood vessels from both exchange nutrients, gases, wastes, etc. After 8 weeks of organogenesis, embryo termed a fetus Morphogenesis is Cells Changing Shape and Moving Relative to Each Other Animal cells change shape using cytoskeleton o E.g., formation of neural tube Microtubules elongate cells Perpendicular microfilaments narrow the apex: make cell wedge-shaped Animal cells move using cytoskeleton o Crawl much like an amoeba Cells form stable tissues using cell adhesion molecules (CAMs); usually glycoproteins on cell surface o Allow cells to recognize others and bind them with specific receptors Migration of cells also mediated by extracellular matrix: mesh of macromolecules outside of cells o Migrating cells have receptors that bind matrix and neighboring cells to control where they are suppose to be Different cells have specific receptor proteins What is the Genetic Basis of all this All cells have the same genes, but different cells have different structures and functions o Depends on which genes are expressed at what time How do we think this works o 1. As cleavage proceeds, cells differentiate Starts with asymmetrical distribution of cytoplasmic determinants Dividing it up leads to different cells Specify body axes, gene expression, etc. o 2. Once asymmetries set up, further differentiation depends upon interactions between cells Induction: changes in gene expression based upon such interactions Cell-cell contact and/or signaling molecules As Cell Lines Develop, they Become More Locked into Specific Roles C. elegans: nematode that is very useful for studying the diversification of cells o Small, lives well in the lab o Every adult has exactly 959 cells Can make a fate map of cell differentiation by: o Watching cells divide o Destroy certain cells and see what doesn’t develop Conlusions: o Older cells are always derived from certain cell lines with unique factors o As cell lines develop, they lose their developmental potential: they can become fewer different types of cells Animals Differ in the Timing of Losing Their Developmental Potential Frog body axes set by distribution of yolk & location of fertilization o Animal vegetal, anterior posterior o Sperm entry gray crescent, ventral dorsal o Left and right by default Among amniotes, polarity not set so early o Body axes can depend on initial orientation of sperm and egg o E.g., mammal cells remain totipotent until 16-cell stage: at 8-cel stage, each blastomere can still become an embryo However, even in mammals eventually cells lose developmental potential o Once they are different they can interact with each other: induction Pattern Formation is Controlled by Induction Induction is involved in pattern formation by providing positional information o E..g, limb development in a chick Limbs begin as mesodermal limb buds, covered in layer of ectoderm; three axes o Proximal distal: shoulder to finger o Anterior to posterior: thumb to pinkie o Dorsal ventral: knuckle to palm As with growth factors in plants, positional information comes from gradients Two important organizer regions o Apical ectodermal ridge (AER): at tip of bud Secretes growth factor that extends limb bud o Zone of polarizing activity (ZPA): posterior, proximal location Organizes anterior posterior development: furthest become anterior Experimentally ass anterior ZPA: get “mirrored” limb