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Lecture 32: Gene Expression and Development

  1. Homeotic mutants

    1. Definition:
      • Bateson collected monstrosities in which one body part had been turned into another.
      • Called this homeosis where homeo means"like".

    2. Description of Drosophila mutants worked on by Ed Lewis and Tom Kaufman

      1. bithorax has T3 segment of thorax converted into T2 segment and has halteres converted into wings

      2. antennapedia has antenna converted into legs

      3. These mutants define two gene complexes each of which contains several homeotic genes located close to each other on chromosome 3.

    3. Molecular biology of homeotic mutants

      1. each gene codes for a slightly different protein
      2. each protein functions as a DNA binding protein that either activates or inhibits transcription
      3. the DNA binding domain in each gene codes for a 60 amino acid segment

    4. Regulation of homeotic genes

      1. homeotic genes turned on by"gap" genes like Krupple that are active earlier in development
      2. each homeotic gene maintains its own expression and maintains the differentiated state

    5. Homeotic genes occur in mammals (mouse and human)

      • the human Hox mutant"foxy feet" demonstrates a link between 5 digits and fertility

    6. Evolutionary conservation of developmental regulation is demonstrated by the homeo gene homologies across the animal groups.

  2. Sexual Development in Humans

    1. Germ cells are formed in the 6th to 10th week in the yolk sac and migrate by amoeboid movement into the gonads
    2. Gonads develop as bulges near the embryonic kidney and develop into a sac with a core
      1. If germ cells are XX, they migrate to the walls of the gonad (cortex); core (medulla) degenerates; gonads become ovaries.
      2. If germ cells are XY, they migrate to the core (medulla); cortex atrophies; gondads become testes
      3. NOTE: XO (Turner - external female with streak gonads) or XXY (Klinefelter - external male with immature testes) individuals have gonads that do not mature.
    3. Internal genitalia arise from Mullerian ducts(female) or Wolffian ducts(male).
      1. At 8 to 10 weeks, embryo has neutral gonads with two duct systems (Mullerian and Wolffian) joined at the lower end.
      2. At the 13th week, gonads differentiate in response to germ cell invasion.
        1. If XX, no hormones released; Mullerian ducts develop into oviducts (Fallopian tubes), uterus, and upper portion of vagina; Wolffian ducts disappear without stimulation from testosterone.
        2. If XY, gonads produce Mullerian duct inhibitor (MDI) which causes Mullerian duct to disappear; gonads produce testosterone which causes Wolffian ducts to develop into sperm collecting apparatus - epididymis, sperm duct (vas deferens), and seminal vesicle; conversion of testosterone to dyhydrotestosterone (DHT) causes development of prostate gland.
      3. NOTE: basic internal sex is female; male development depends on hormone production (testosterone, DHT, and MDI)
    4. External genitalia arise from common embryonic rudiments:
      1. Mullerian and Wolffian ducts join to a common duct (cloaca) which eventually provides an exit for eggs or sperm and urine
      2. The cloaca contacts the surface of the embryo to produce a bulge consisting of a genital tubercle with genital folds and a larger pair of genital swellings.
      3. If DHT is absent (XX):
        • tubercle develops as clitoris
        • folds develop as labia minora and distal vagina
        • swelling develops as labia majora
      4. If DHT is present (XY):
        • tubercle develops as penile glans (tip)
        • folds develop as penile shaft
        • swelling develops as scrotum
    5. At puberty (10-12 years in XX, 12-14 years in XY):
      1. females in response to
        • pituitary hormones: produce eggs; menstrual cycle begins; breasts develop; pelvic bones enlarge; hair grows in armpits and pubis.
      2. males in response to
        • testosterone: voice deepens; muscle mass increases; phallus and scrotum grow; hair in armpits and pubis; sperm produced.
        • dihydrotestosterone (DHT): prostate growth; facial hair produced; recession of hairline; acne.
    6. Developmental abnormalities
      1. XY"female"; Congential Insensitivity to Androgen Syndrome (CAIS) or Testicular Feminization (tfm)
        • chromosomal sex is XY; gonads are testes; ducts are male
        • external genitalia are female; vagina ends in blind pouch
        • defect in receptor to testosterone; cells unable to bind androgens and cannot respond even though normal male levels of androgen are present
        • inherited as X-linked trait
        • mothers of affected"females" have some cells which bind androgen and some cells which do not
        • psychologically female
      2. XY"female then male" - Guevedoces
        • chromosomal sex is male (XY); gonads are testes, ducts are male
        • external genitalia appear at birth as female; clitoral-like penis, undescended tests so scrotum appears like labia
        • at puberty, penis enlarges, testes descend, male characters appear,
        • associated with reduced enzymatic activity involving conversion of testosterone to DHT
        • autosomal recessive inheritance
      3. XX"male" - Congenital Androgenital Syndrome (CAS)
        • chromosomal sex is female (XX); gonads are ovaries with oviducts, uterus, and vagina
        • external genitalia appear male-like with penis and scrotum but vaginal opening may be present
        • adrenal glands larger than normal and produce increased amounts of testosterone
        • inherited as autosomal recessive
      4. Terms Used in Describing Babies With Ambiguous Genitals
        • herms = hermaphrodites: testicular and ovarian tissue present
        • ferms = female pseudohermaphrodites: genetic females with partly masculinized external sex organs
        • merms = male pseudohermaphrodites: genetic males who don't fully masculinize during development
      5. Hypospadias
        A malformation in which the urethra opens on the side of the penis or on the scrotum, rather that at the end of the penis. This occurs as a part of a number of inherited syndromes as well as on a sporadic, apparently non-inherited basis. Recent evidence suggests that the frequency of hypospadias has doubled from 1970 to 1993 with a current rate of about 80 per 10,000 male births or almost one out of every 100 boys born. This increase has been seen in all four regions of the U.S. as well as in five European countries.

This document maintained by Robert J. Huskey.
Last update on November 16, 1999.