GENETICS The Content Introduction

GENETICS

The Content § § § Introduction to genetics The Molecular Basis of Inheritance Laws of Gregor Mendel The interaction of genes Sex genetics Gene linkage and crossing over Variation Human Genetics Population genetics Structure and function of genes Gen regulation in prokaryotes and eukaryotes Fundamentals of genetic selection

Introduction to Genetics • GENETICS – branch of biology that deals with heredity and variation of organisms. • Chromosomes carry the hereditary information (genes) • Arrangement of nucleotides in DNA • DNA RNA Proteins

• Chromosomes (and genes) occur in pairs Homologous Chromosomes • New combinations of genes occur in sexual reproduction – Fertilization from two parents

Gregor Johann Mendel • Austrian Monk, born in what is now Czech Republic in 1822 • Son of peasant farmer, studied Theology and was ordained priest Order St. Augustine. • Went to the university of Vienna, where he studied botany and learned the Scientific Method • Worked with pure lines of peas for eight years • Prior to Mendel, heredity was regarded as a "blending" process and the offspring were essentially a "dilution"of the different parental characteristics.

Mendel’s peas • Mendel looked at seven traits or characteristics of pea plants:

• In 1866 he published Experiments in Plant Hybridization, (Versuche über Pflanzen. Hybriden) in which he established his three Principles of Inheritance • He tried to repeat his work in another plant, but didn’t work because the plant reproduced asexually! If… • Work was largely ignored for 34 years, until 1900, when 3 independent botanists rediscovered Mendel’s work.

• Mendel was the first biologist to use Mathematics – to explain his results quantitatively. • Mendel predicted The concept of genes That genes occur in pairs That one gene of each pair is present in the gametes

Genetics terms you need to know: • Gene – a unit of heredity; a section of DNA sequence encoding a single protein • Genome – the entire set of genes in an organism • Alleles – two genes that occupy the same position on homologous chromosomes and that cover the same trait (like ‘flavors’ of a trait). • Locus – a fixed location on a strand of DNA where a gene or one of its alleles is located.

• Homozygous – having identical genes (one from each parent) for a particular characteristic. • Heterozygous – having two different genes for a particular characteristic. • Dominant – the allele of a gene that masks or suppresses the expression of an alternate allele; the trait appears in the heterozygous condition. • Recessive – an allele that is masked by a dominant allele; does not appear in the heterozygous condition, only in homozygous.

• Genotype – the genetic makeup of an organisms • Phenotype – the physical appearance of an organism (Genotype + environment) • Monohybrid cross: a genetic cross involving a single pair of genes (one trait); parents differ by a single trait. • P = Parental generation • F 1 = First filial generation; offspring from a genetic cross. • F 2 = Second filial generation of a genetic cross

Monohybrid cross • Parents differ by a single trait. • Crossing two pea plants that differ in stem size, one tall one short T = allele for Tall t = allele for dwarf TT = homozygous tall plant t t = homozygous dwarf plant TT tt

Monohybrid cross for stem length: P = parentals true breeding, homozygous plants: F 1 generation is heterozygous: TT tt (tall) (dwarf) Tt (all tall plants)

Punnett square • A useful tool to do genetic crosses • For a monohybrid cross, you need a square divided by four…. • Looks like a window pane… We use the Punnett square to predict the genotypes and phenotypes of the offspring.

Using a Punnett Square STEPS: 1. determine the genotypes of the parent organisms 2. write down your "cross" (mating) 3. draw a p-square Parent genotypes: TT and t t Cross TT tt

Punnett square 4. "split" the letters of the genotype for each parent & put them "outside" the p-square 5. determine the possible genotypes of the offspring by filling in the p-square 6. summarize results (genotypes & phenotypes of offspring) T TT tt t t Tt Tt T Tt Genotypes: 100% T t Tt Phenotypes: 100% Tall plants

Monohybrid cross: F 2 generation • If you let the F 1 generation self-fertilize, the next monohybrid cross would be: Tt (tall) T T t t TT Tt Tt tt (tall) Genotypes: 1 TT= Tall 2 Tt = Tall 1 tt = dwarf Genotypic ratio= 1: 2: 1 Phenotype: 3 Tall 1 dwarf Phenotypic ratio= 3: 1

Secret of the Punnett Square • Key to the Punnett Square: • Determine the gametes of each parent… • How? By “splitting” the genotypes of each parent: If this is your cross T T t t The gametes are: T T t t

Once you have the gametes… T T t t Tt Tt

Shortcut for Punnett Square… • If either parent is HOMOZYGOUS T T t t T Tt • You only need one box! t Genotypes: 100% T t Phenotypes: 100% Tall plants

Understanding the shortcut… t t t T Tt Tt = T Tt Tt Genotypes: 100% T t Phenotypes: 100% Tall plants T Tt

If you have another cross… • A heterozygous with a homozygous T t You can still use the shortcut! t t T Tt t t Genotypes: 50% T t 50 % t t Phenotypes: 50% Tall plants 50% Dwarf plants

Another example: Flower color For example, flower color: P = purple (dominant) p = white (recessive) If you cross a homozygous Purple (PP) with a homozygous white (pp): PP Pp pp ALL PURPLE (Pp)

Cross the F 1 generation: Pp Pp P P p p PP Genotypes: 1 PP 2 Pp 1 pp Pp Pp pp Phenotypes: 3 Purple 1 White

Mendel’s Principles • 1. Principle of Dominance: One allele masked another, one allele was dominant over the other in the F 1 generation. • 2. Principle of Segregation: When gametes are formed, the pairs of hereditary factors (genes) become separated, so that each sex cell (egg/sperm) receives only one kind of gene.

Dihybrid crosses • Matings that involve parents that differ in two genes (two independent traits) For example, flower color: P = purple (dominant) p = white (recessive) and stem length: T = tall t = short

Dihybrid cross: flower color and stem length TT PP tt pp (tall, purple) Possible Gametes for parents (short, white) tp tp tp TP Tt. Pp Tt. Pp TP Tt. Pp and t p Tt. Pp TP TP Tt. Pp tp Tt. Pp F 1 Generation: All tall, purple flowers (Tt Pp)

Dihybrid cross: flower color and stem length (shortcut) TT PP tt pp (tall, purple) (short, white) Possible Gametes for parents T P TP tp t p Tt Pp F 1 Generation: All tall, purple flowers (Tt Pp)

Dihybrid cross F 2 If F 1 generation is allowed to self pollinate, Mendel observed 4 phenotypes: Tt Pp (tall, purple) Possible gametes: TP Tp t. P tp (tall, purple) TP Tp t. P TP TTPp Tt. PP Tp TTPp TTpp Tt. Pp t. P Tt. Pp tp Tt. Pp Ttpp tt. PP tt. Pp ttpp Four phenotypes observed Tall, purple (9); Tall, white (3); Short, purple (3); Short white (1)

Dihybrid cross 9 Tall purple TP Tp t. P TP TTPp Tt. PP 3 Tall white Tp TTPp TTpp Tt. Pp t. P Tt. Pp tp Tt. Pp 3 Short 1 Short Ttpp tp Tt. Pp Ttpp tt. PP tt. Pp ttpp purple white Phenotype Ratio = 9: 3: 3: 1

Dihybrid cross: 9 genotypes Genotype ratios (9): 1 TTPP 2 TTPp 2 Tt. PP 4 Tt. Pp 1 TTpp 2 Ttpp 1 tt. PP 2 tt. Pp 1 ttpp Four Phenotypes: Tall, purple (9) Tall, white (3) Short, purple (3) Short, white (1)

Principle of Independent Assortment • Based on these results, Mendel postulated the 3. Principle of Independent Assortment: “Members of one gene pair segregate independently from other gene pairs during gamete formation” Genes get shuffled – these many combinations are one of the advantages of sexual reproduction

Relation of gene segregation to meiosis… • There’s a correlation between the movement of chromosomes in meiosis and the segregation of alleles that occurs in meiosis

Test cross When you have an individual with an unknown genotype, you do a test cross. Test cross: Cross with a homozygous recessive individual. For example, a plant with purple flowers can either be PP or Pp… therefore, you cross the plant with a pp (white flowers, homozygous recessive) P ? pp

Test cross • If you get all 100% purple flowers, then the unknown parent was PP… P P p • If you get 50% white, 50% purple flowers, then the unknown parent was Pp… Pp Pp Pp P p p p Pp pp

Dihybrid test cross? ? If you had a tall, purple plant, how would you know what genotype it is? tt pp ? ? 1. 2. 3. 4. TTPP TTPp Tt. PP Tt. Pp

Beyond Mendelian Genetics: Incomplete Dominance Mendel was lucky! Traits he chose in the pea plant showed up very clearly… One allele was dominant over another, so phenotypes were easy to recognize. But sometimes phenotypes are not very obvious…

Incomplete Dominance Snapdragon flowers come in many colors. If you cross a red snapdragon (RR) with a white snapdragon (rr) RR rr You get PINK flowers (Rr)! Genes show incomplete dominance when the heterozygous phenotype is intermediate. Rr

Incomplete dominance When F 1 generation (all pink flowers) is self pollinated, the F 2 generation is 1: 2: 1 red, pink, white Incomplete Dominance R R r r R R Rr Rr rr

Incomplete dominance What happens if you cross a pink with a white? A pink with a red?

Summary of Genetics • Chromosomes carry hereditary info (genes) • Chromosomes (and genes) occur in pairs • New combinations of genes occur in sexual reproduction • Monohybrid vs. Dihybrid crosses • Mendel’s Principles: – Dominance: one allele masks another – Segregation: genes become separated in gamete formation – Independent Assortment: Members of one gene pair segregate independently from other gene pairs during gamete formation

How can we predict the possible traits of an offspring, considering the traits of parental generations. ?

HOW TO SOLVE GENETICS PROBLEMS 1. 2. 3. Read the problem. Determine what traits are dominant and which are recessive. Often you must marshal background knowledge to do this – which may not be explicitly mentioned in the problem. Are any letters assigned to the genes? If not, make some up. We usually take the dominant characteristic and use the first letter of that word. For example, if polydactyly ( extra fingers ) is dominant over the normal five–fingered condition , we would pick P for the dominant gene, and small p for the recessive normal allele.

4. Determine, if possible, the genotypes of the parents. In 9 out of 10 problems this information is given, or at least implied. Sometimes you have to deduce it from other information given. Write it down so that you can remember what it is, e. g. Pp. 5. Determine all the possible kinds of gametes that can be made by each parent. Be careful, remember that a gamete can ordinarily receive only one gene of a pair of alleles. This is the part that most people have trouble with! e. g. P p.

6. Make a Punnett square, using each of the gametes for one parent across the top of each column, those of the other parent go vertically. If you have done step 5 properly you shouldn’t have any trouble with this step. 7. Work the cross carefully 8. Now read the problem again. Find out exactly what it is asking for. Don’t assume too much. This is another place where many people get lost.

9. In most problems, these steps should get you through adequately. Some are slightly altered – for example, if the genotype of one of the parents is unknown, and that is what the problem wants you to discover. You may assign that parent something like A_ or __ genotype and see if that helps. Put the offspring genotypes in the square and work backward. Remember this won’t get all the problems – there is still nothing like real understanding – but it can help organize your attack on a genetic problem. and of curse, unless you understand the terms, such as homozygous, heterozygous, dominant, recessive, allele, and so on, you cannot begin to think of working problems.

10. Finally, the actual genetic information you need to solve these problems often appears concealed rather than revealed by the wording of the problem. learn to translate such a sentence, “Mary is normally pigmented but had an albino father”, into its logical consequence: “Mary is heterozygous for albinism” and then into “Mary is Cc”. Notice that, in this kind of a problem you may need to solve several subsidiary problems before you can proceed with the final solution.

Solve the genetic problems: 1. The so-called "blue" (really gray) Andalusian variety of chicken is produced by a cross between the black and white varieties, both of which breed true (i. e. , both are homozygous). What color chickens (and in what proportions) would you expect if you crossed two blues? a blue and a black? 2. In four o'clock, red color exhibits incomplete dominance over white; when both exist together, the flowers are pink. a. In a cross between a red flower and a white one, what is the genotype of the offspring? b. What is the genotypic ratio of the F 2 generation if two of the F 1 from (a) are crossed? c. List the genotypes of offspring produced by a cross between the F 1 generation and red parent.

• A TT (tall) plant is crossed with a tt (short plant) What percentage of the off spring will be tall? __ • In pea plants purple flowers are dominant to white flowers: - If two white flowered plants are cross, what percentage of their offspring will be white flowered? • - A white flowered plant is crossed with a plant that is heterozygous purple for the trait. What is the genotype ratio?

Relationship between Gene and Allele • Gene - a segment of DNA that controls a specific trait. • Allele - the alternate (or contrasting) form of a gene.

Difference between Dominant and Recessive • Dominant - refers to an allele that masks the expression of another allele for the same trait. • Recessive - the allele that is masked by the presence of another allele for the same trait. – Unattached (right) earlobes is dominant to attached earlobes (left). – A widow’s peak (left) is a dominant trait over a rounded face.

Difference between Genotype and Phenotype • Genotype - genetic makeup of an organism; refers to the alleles for a trait. • Phenotype - physical or outward expression of the alleles for that trait. (What it looks like) • Genotype codes ( or determines) for phenotype

Incomplete Dominance • Occurs when two or more of the alleles influence phenotype, resulting in a phenotype intermediate between the dominant and recessive trait. – The heterozygous individual (Rr) shows the intermediate trait of pink. – RR (homozygous dominant) is red flower – rr (homozygous recessive) is white flower color.

Codominance • Occurs when both alleles for a gene are expressed in heterozygous offspring. • Neither the dominant or recessive allele is dominant, nor do they blend in phenotype.

Questions 1. What is the ratio of a dihybrid cross between two heterozygous traits? 2. In an dihybrid cross between two heterozygous parents, what is the probability of obtaining an offspring that is homozygous for both traits? 3. What is the most likely explanation for two parents with dominant phenotypes producing offspring with a recessive phenotype? 4. You cross a red-flowering plant with a yellow-flowering plant and notice that some of the offspring have orange flowers. What is the most likely explanation for this occurrence? 5. Explain the difference between the P generation, F 1 generation, and F 2 generation.

HEREDITARY JUVENILE GLAUCOMA

ALBINISM

Extensions to Mendel

• Untwisting and replication of DNA Figure 10. 4 B

INTERPHASE PROPHASE Centrosomes (with centriole pairs) Early mitotic spindle Centrosome Chromatin Nucleolus Nuclear envelope Figure 8. 6 Plasma membrane Chromosome, consisting of two sister chromatids Fragments of nuclear envelope Centrosome Kinetochore Spindle microtubules

• The human life cycle • Meiosis is a special form of cell division that produces gametes Haploid gametes (n = 23) Egg cell haploid Sperm cell haploid MEIOSIS FERTILIZATION Diploid zygote (2 n = 46) Multicellular diploid adults (2 n = 46) Mitosis and development Figure 8. 13

MEIOSIS I: Homologous chromosomes separate INTERPHASE Centrosomes (with centriole pairs) Nuclear envelope Figure 8. 14, part 1 PROPHASE I METAPHASE I Microtubules attached to Spindle kinetochore Sites of crossing over Chromatin Sister chromatids Tetrad Metaphase plate Centromere (with kinetochore) ANAPHASE I Sister chromatids remain attached Homologous chromosomes separate

Looking for the appropriate size: genetics under control Crazy about Biomedicine– May 2013 Ana Ferreira Development and Growth Control Lab

Summary I. Genetics Definition Mendelian Genetics Drosophila melanogaster: The Fruit Fly Historical view of the fly Drosophila as a model organism II. Developmental Biology Definition Historial view III. Growth Control: The different parameters Our system: the fly wing Systemic vs Organ-autonomous Growth Control Size Control and Human Disease

I. Genetics

Genetics is a discipline of biology, is the science of genes, heredity, and variation in living organisms Genetics deals with the molecular structure and function of genes, gene behavior in the context of a cell or organism, patterns of inheritance from parent to offspring, and gene distribution, variation and change. GENETICS + ORGANISM EXPERIEN in populations = FINAL OUTCOME

Mendelian and Classic Genetics Gregor Mendel (1822 - 1884) studied the nature of inheritance in plan observed that organisms inherit traits by way of discrete units of inheritance, which are now called traced the inheritance patterns of genes certain traits in plants and described them mathematically

Discrete Inheritance and Mendel’s Laws studied the segregation of heritable traits in pea plants 29, 000 pea Grow easily, develop pure-bred strains, and control their pollination Pisum sativum

Discrete Inheritance and Mendel’s Laws

Discrete Inheritance and Mendel’s Laws Dominant trait Alleles: is one of a number of alternative forms of the same gene

Discrete Inheritance and Mendel’s Laws

Discrete Inheritance and Mendel’s Laws 3: 1 ratio diploid species: each individual has two copies of each gene, one inherited from each parent organisms with two copies of the same allele of a given gene are organisms with two different alleles of a given called homozygous gene are called heterozygous

Discrete Inheritance and Mendel’s Laws homozygous heterozygous (WW) (Ww) (ww) Purple White

Discrete Inheritance and Mendel’s Laws homozygous heterozygous Genotype (set of alleles) Phenotype (observable traits) (WW) (Ww) (ww) Purple White W W one allele is other allele is called recessive dominant

Discrete Inheritance and Mendel’s Laws

Discrete Inheritance and Mendel’s Laws 3: 1 ratio

Discrete Inheritance and Mendel’s Laws

Discrete Inheritance and Mendel’s Laws 1 The Law of Dominance: In a cross between contrasting homozygous individuals, only one form of the trait will appear in the F 1 generation - this trait is the dominant trait

Discrete Inheritance and Mendel’s Laws 1 The Law of Dominance: In a cross between contrasting homozygous individuals, only one form of the trait will appear in the F 1 generation - this trait is 2 the dominantof Segregation: when any individual The Law trait produces gametes, the copies of a gene separate so that each gamete receives only one copy (allele) - a gamete will receive one allele or the other

Discrete Inheritance and Mendel’s Laws 1 The Law of Dominance: In a cross between contrasting homozygous individuals, only one form of the trait will appear in the F 1 generation - this trait is 2 the dominantof Segregation: when any individual The Law trait produces gametes, the copies of a gene separate so that each gamete receives only one copy (allele) - a gamete 3 will receive one allele or the other The Law of Independent Assortment: alleles responsible for different traits are distributed to gametes (and thus the offspring) independently of each other

Drosophila melanogaster

Drosophila melanogaster: the fruit fly

Historical view of Drosophila Charles W. Woodworth (1865 - 1940) 1900 – First to breed Drosophila in the

Historical view of Drosophila Thomas Hunt Morgan (1866 - 1945) 1900 – Started to work with Drosophila (study of mutation) 1910 – First mutation was found (white 1911 – Genes are on chromosomes 1933 – Nobel Prize in Physiology or Me for the role played by chromoso heredity

Historical view of Drosophila

Historical view of Drosophila Hermann Joseph Müller (1890 - 1967) 1946 – Nobel Prize in Physiology or Medi for the discovery of the genetics e of Radiation (X-ray mutagenesis)

Historical view of Drosophila Eric Wieschaus (1947 - ) Janni Nusslein-Volhard Edward B. Lewis (1942 - ) (1918 - 2004) 1995 – Nobel Prize in Physiology or Medicine for revealing the genetic control of embryonic development

Historical view of Drosophila Jules A. Hoffmann (1941 - ) Bruce A. Beutler Ralph M. Steinman (1957 - ) (1943 – 2011) 2011 – Nobel Prize in Physiology or Medicine for the discovery of the dendritic cell and its role in

Why Drosophila melanogaster is such a good model organism ?

Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400 -500 eggs Easy to maintain in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400 -500 eggs Easy to maintain and manipulate in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

Why Drosophila melanogaster is such a good model organism ? Short Life Cycle (Temperature Dependent – 10 days @ 25ºC) Each Female lays 400 -500 eggs Easy to maintain and manipulate in the Lab (low cost) Suitable of Genetic Manipulation Extensive set of genetic tools available Simple karyotype: 4 pairs of large chromosomes (3 autosomes + sexual chromosomes) Gene Sequence Conservation with humans: 60% Functional conservation of regulatory and biochemical pathways with humans

Why Drosophila melanogaster is such a good model organism ?

Drosophila melanogaster Life Cycle Growth Phase

Drosophila melanogaster: why is such a potent genetic organism ? Genome fully sequenced Mutant animals are readily obtainable Huge amount of transgenic lines available Targeting gene expression in a temporal and spatial fashion

Targeting gene expression: Gal 4 -UAS System Driver line Responder line Big collection of both Driver and Responder Lines available Temperature Dependence of the Driver Line

Targeting gene expression: Gal 4 -UAS System

II. Developmental Biology

Developmental Biology

Historical Perspective – The first steps Aristotle (384 – 322 AC) Study of the Development of the chick The semen of the male provides the “form” or soul and the female the unorganized matter (menstrual blood) allowing the embryo to grow: EPIGENESIS Theory of Preformationism: organs with their own shape expand Theory of Spontaneous Generation: life of invertebrates emerges from non -living matter (“nothing”)

Historical Perspective - Renaissance Leonardo da Vinci (1452 - 1519) Dissection of human corpses Drawings of the vascular and system First drawing of the human fetus in the utero Views of a Fetus in the Womb Leonardo da Vinci, ca. 1510 -1512

Historical Perspective - Renaissance

Historical Perspective - Renaissance Antonie van Leeuwenhoek (1632 - 1723) Discovered the microorganisms: animacule Discovered the spermatozoa “…now that I have discovered that the animalcules also occur in the male seed of quadrupeds, birds and fishes…, I assume with even greater certainty than before that a human being originates not from an egg but from an animalcule that is found in the male semen”

Historical Perspective - Renaissance PREFORMATIONISM organisms develop from miniature versions of themselves Nicolaas Hartsoeker in 1695

Historical Perspective - Renaissance Reiner de Graaf (1641 - 1673) Discovered the follicles of the ovary (known as Graafian follicles), in which the individual egg cells Rejecting the preformationism are formed

Historical Perspective "ontogeny recapitulates phylogeny” Ernst Haeckel (1834 - 1919) Recapitulation Theory / Embryological Parallelism developing embryo to from adult, animals go through

Historical Perspective Karl Ernst von Baer (1792 - 1876) Opposing view that the early general forms diverged into four major groups of specialized forms without ever resembling the adult of another species

Historical Perspective August Weismann (1834 - 1914) Germ plasm theory inheritance only takes place by means of the germ cells—the gametes Other cells of the body—somatic cells—do not function as agents of heredity

Historical Perspective Experimental Embryology Wilhelm Roux 1888 – Experiment destroying the frog embryo (in the two cells stage) Hans Driesch 1892 – Separates de early 4 cells stage embryo of the sea urchin Hans Spemann and Hilde Mangold 1918 -1924 – Transplants of cells from one embryo to another induced particular tissues or organs – embryonic induction. Nobel Prize in 1935

Are Developmental Biology and Genetic Linked ?

III. Growth Control

How are differences in size achieved ?

What determines differences in size ? Size of an organ/animal = number of cells of the cells + size + space between cells Size of an organ/animal = number of cells + size of the cells Cell Number + Cell Size similar Cell Division + Cell Death Cell Growth

What determines differences in size ? Cell Division / Proliferation: increase in cell number by one cell (the "mother cell") dividing to produce two Cell Death / Apoptosis: is death of a cell in any form, "daughter cells" mediated by an intracellular program (DNA Cell Growth: and protein cell mass (protein synthesis fragmentation increase in degradation) and organelle biogenesis) Cell Cycle

How organs achieve a particular size and pattern ?

Drosophila imaginal discs: proliferative tissues

Drosophila wing imaginal disc 20 -30 cells Embryo Larvae wing Adult notum 50, 000 cells

Drosophila wing imaginal disc development

Body Size Regulation

Systemic vs organ-autonomous growth control § Long range signaling molecules (hormones…) § Cell autonomous growth § Environmental factors (nutrition…) promoters

Systemic growth control SYSTEMIC GROWTH CONTROL GROWTH RATE DEVELOPMENTAL TIMING (moults+pupariation)

Systemic growth control DEVELOPMENTAL TIMING Ecdysone Ring gland Fat body Insulin Brain nutrients Hemolymph (fly ‘blood’) FEEDING GROWTH Gut

Organ-autonomous growth control Transplants Experiments: when a small organ is transplanted into an adult organism it grows to its normal final size (even in between different species) Regeneration Experiments

Size Control and Human Disease Cancer: tumor initiation, metastasis Organ hypertrophy or atrophy Growth Pathways Insulin pathway d. Myc oncogene Hippo pathway TGFb signaling (Dpp) Wnt signaling (Wg) Diabetes and Obesity Regeneration and Stem Cell Biology Drosophila was, is and will be important for Human Biolo

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Transformation in flies

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