Intermediate Mesoderm Kidney and Gonad Development Gilbert Chapter

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

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

Intermediate Mesoderm: The Urogenital System • Kidneys • Gonads • Respective Ducts

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)

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

• 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

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

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

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

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

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

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?

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

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

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

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

XX mice Transgenic for Sry Gene

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)

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

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

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)

“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

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 1 X, fly is male, if 2 X fly is female • NOT dependent on Y