1. Intermediate Mesoderm: Kidney and Gonad Development Gilbert: Chapter 14, 17

2. Today’s Goals Identify the derivatives of the intermediate mesoderm Describe the basics of Kidney development Describe mechanisms for development of male vs. female gonads –Sex determination in mammals

3. Intermediate Mesoderm: The Urogenital System Kidneys Gonads Respective Ducts

4. Specification of IM Intermediate Mesoderm gets signals from the somitic mesoderm and LP mesoderm (BMP- 4) Specified to form kidney tubule through interactions with the paraxial mesoderm –Signals from paraxial mesoderm induce formation of pronephric duct (Pronephros)

5. If intermediate mesoderm is physically separated from paraxial mesoderm (somites) –Pronephric kidney duct does not form

7. Paraxial Mesoderm is both NECESSARY and SUFFICIENT to induce Intermediate mesoderm If culture Lateral Plate mesoderm and Paraxial mesoderm together in a dish, paraxial mesoderm can induce part of LPM to form Pronephric tubules

8. Basics of Kidney Dev. Functional Unit = Nephron –Contain over 10,000 cells and 12 different cell types, each w/ different functions Kidney Development - 3 major stages –First 2 stages are transient

9. First Stage Around 22 days in humans, 8 days in mice –Pronephric duct arises from the intermediate mesoderm –The cells of the duct begin to migrate posteriorly while those in the anterior region of the duct induce formation of the initial kidney tubules = pronephros

10. In mammals - anterior end of pronephric duct degenerates Posterior end of duct - becomes Wolffian Duct - more on this later

12. Second Stage As the pronephric tubules degenerate: –The middle portion of the Nephric duct forms and induces a new set of kidney tubules = mesonephros –Most anterior tubes degenerate –Posterior tubes will become part of the next stage

13. Third Stage Formation of Metanephros Induced to form by signals from neighboring tissues Other inductions occur nearby to form collecting ducts and ureters to take urine to the bladder

15. Mammalian Sex Determination and Dev. Of the Gonad The gonads are also derived from the intermediate mesoderm Form testes or ovaries –But before they “choose” - come from a common precursor structure = Bipotential Gonad! In the chromosomes - how is sex determination achieved in mammals?

17. Mammalian Gonads are Unique! All other organ rudiments can only become 1 type of organ - –Lung rudiment - only forms a lung But - the bipotential gonad that appears can become either ovary or testes (genital ridge) –Appears around week 4 in human development, remains sexually indifferent until week 7

18. Basics: 2 ducts form in sexually indifferent embryonic stages –Has 2 developing ducts - Müllerian duct and Wolffian duct Based on hormonal interactions - one or the other duct will degenerate, one will function, develop further incorporating into reproductive tracts

20. How it works, simplified In an XX or any other combo lacking a Y chromosome (XO, XXX) –No Y present, gonad develops into ovaries –Ovaries release estrogen –This enables development of Müllerian duct Forms uterus, oviducts, upper end of the vagina Female is the default sex

21. How it works, simplified If Y chromosome is present –SRY gene is expressed –Testes determining factor is produced –Induces formation of testes –Secrete 2 hormones: Anti-Müllerian Hormone Testosterone Causes Müllerian Duct to degenerate Allows Wolffian Duct to connect to developing male gonad

24. XX mice Transgenic for Sry Gene

25. Germ Cells Primordial Germ Cells (PGC’s) (those that will form the haploid germ cells - sperm and egg) don’t form from Intermediate Mesoderm They form during gastrulation (migrate through primitive streak in mammals) Migrate to the genital ridges (ventral portions of developing kidney)

26. Unusual Cases in Sex Determination Androgen Insensitivity - –person is XY, produces SRY gene product, and thus testosterone –No receptor for testosterone! –Have testes, but also make and respond to estrogen –Thus phenotype on the outside is female (secondary sex characteristics) and they have a uterus and oviducts

27. Unusual Cases in Sex Determination XO individuals –Initially develop ovaries, but they degenerate –Appearance is female, have female genital tract, due to prenatal estrogen exposure but sterile

28. Unusual Cases in Sex Determination Pseudohermaphroditism –One type of gonad, but opposite secondary sex characteristics (as in androgen insensitivity) –Female pseudohermaphroditism - gonads are female, but outwardly male - can occur (overproduction of androgen hormones)

29. “True” Hermaphrodites Contain both male and female gonadal tissue Results from abnormalities in primary sex determination (X/Y system) Translocations of Y chromosome INTO X chromosomes –Mosaic gene expression and X-inactivation In some cells one X is expressed, in others, the other X is expressed! See video clip

30. Note: The mammalian X/Y system of sex determination is not used in all species For most species, other systems are used In Drosophila a ratio system is used –Ratio between number of X chromosomes and number of autosomes if there is 1X, fly is male, if 2X fly is female NOT dependent on Y