Transcript Intermediate Mesoderm: Kidney and Gonad

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 (BMP4)
• 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 1X, fly is male, if 2X fly is female
• NOT dependent on Y