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Unformatted text preview: I. Pattern Formation (Drosophila) II. Differentiation
th 6 ed: 406-418 7th ed: 412-425; 431-432 th ed: 368-372, 8 412-416, 445 Pattern formation: setting up basic body plan so tissues & organs develop in the right place. Plan is established before the structures themselves develop. Example in animals: gastrulation. Problem: little is known about molecular details of how this works in humans & other animals! Lots is known about pattern formation in Drosophila. Some proteins & principles are turning out to be the same in humans. Drosophila develoment 1. Fertilized egg develops into embryo 2. Embryo hatches into larva (no gastrulation!) 3. Larva metamorphoses into adult. Early event in pattern formation: setting up anterior-posterior axis (which end is the head). bicoid mRNA (a cytoplasmic determinant) is stored in egg; concentrated at anterior end. After fertilization, the mRNA is translated into Bicoid protein in the embryo. Bicoid protein in early embryo. Bicoid protein gradient sets up the A-P axis! Mutation of bicoid that destroys its function gives embryo with two back ends; no front end. Embryonic lethal: mutation that gives defective protein. As a result, organism dies early in development. Defects in dead embryo can give information on normal function of gene. Bicoid protein: a transcription factor. It stimulates expression of certain genes. Segments: basic units of pattern formation in flies; both embryo & adult. Adult structures develop from segments in the larva. Bicoid protein stimulates expression of genes that control segment formation. Cells in embryo that have more Bicoid develop into more anterior segments. The genes whose expression Bicoid enhances code for: 1. Transcription factors 2. Inducer proteins These control development of segments. A network of interacting genes control segment formation. (you don’t have to know any of this) After segment formation, homeotic genes control development of each segment into an adult structure. Homeotic genes - form a gene family - code for transcription factors that share a short conserved sequence; “homeobox” that encodes a “homeodomain”. Each one is expressed in a different segment. Homeotic mutation yields a defective homeotic gene. If this happens; another homeotic gene takes over. Result: substitution of one body part for another. normal fly head homeotic mutant (legs replace antennae) Order of homeotic genes on the chromosome parallels order of body parts they control (significance unknown). a fly chromosome Homeobox-containing genes are also found in animals; also affect development.
mouse chromosomes mouse embryo Differentiation: a principle of development Zygote & early embryo cells are undifferentiated - all look the same - do not make proteins characteristic of any individual tissue in adult
blastocyst Most cells in adult are differentiated; have adopted a particular fate. -May have distinctive appearance. -Express specialized genes to make proteins only found in that tissue Zygote and early embryo cells are totipotent: can give rise to all cells of adult. Most differentiated cells in animals are committed to that fate; cannot give rise to cells of a different type. i.e. - liver cell can divide; but can only give rise to other liver cells. - nerve cells can’t divide Differentiation occurs as development proceeds; cells become committed to one fate.
blastocyst can give rise to any cell in organism can only give rise to liver cells Stem cells undifferentiated cells that can differentiate into other cell types. Embryonic stem cells: cells from blastocyst; can differentiate into all tissues. different culture conditions Process of commitment to a differentiated fate occurs via sequential steps during development. Pluripotent stem cells are present even in adult. They can differentiate into some but not all cell types. Example: stem cells in bone marrow of adult can differentiate into red or white blood cells (fight disease) - but not into other cell types.
red blood cell white blood cell Growing stem cells in culture may be useful for: 1. Research on differentiation 2. (for the future) Replacing damaged cells in patients (example: certain brain cells in Parkinson’s disease) Example of sequential steps in differentiation: muscle. Muscle tissue; highlydifferentiated. - expresses muscle fiber proteins - has distinctive structure; cells fuse to form syncytia; large cells with many nuclei & muscle fibers. Muscle fibers in a muscle cell.
Muscle contracts when fibers slide past each other. actin fibers (with other proteins) myosin fibers Early in development, a certain embryonic precursor cell is a pluripotent stem cell: could give rise to muscle, fat, or cartilage cells. Step 1: Specific conditions trigger expression of a master regulatory gene called myoD. Master regulatory genes: protein products commit a cell to a particular fate Cell is now a myoblast and is committed to becoming a muscle cell. Myoblast - looks undifferentiated - does not make any muscle fiber proteins -makes MyoD -is committed or “determined” to become a muscle cell
myoD gene genes for muscle fiber proteins MyoD is a transcription factor. Step 2: It stimulates expression of other transcription factors; these stimulate expression of genes for muscle fiber proteins & proteins that cause cell differentiation. Effect of MyoD: muscle fiber proteins are expressed; muscle differentiates. Sum: Determination occurs before differentiation
Determination myoblast Differentiation Differentiation is sometimes reversible. This is easier in plants than animals. root slice fragments new embryo liquid broth whole plant In animals; differentiation gets harder to reverse as development proceeds... but can occasionally be done. Animal cloning: growing an entire new organism from the nucleus of a differentiated adult cell. Animal cloning: nucleus from an adult cell transplanted into the cytoplasm of an egg. Goal; being in egg cytoplasm convinces adult nucleus it’s the nucleus of a zygote. 1. Remove & discard the nucleus from an egg. 2. Fuse the egg with a differentiated cell. Rarely, an embryo forms & develops normally. cloned lamb! ...
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- Fall '08