Transcript No Slide Title

SEXUAL DEVELOPMENT
GAMETOGENESIS
EMBRYOLOGY: Cellular mechanisms
She arrived by default.
He was miffed.
:
:
Am I going dotty, or what?
German Umlaut to modify a vowel
:
::
MULLERIAN DUCT
naive
:
Paraoophoron
Zoological
:
:
French trema to indicate emphasis
English diaeresis - to show second ‘o’ is pronounced
independently
SEXUAL DEVELOPMENT
OVARY
UTERINE
TUBE
VAGINA
UTERUS
:
VULVA
MULLERIAN DUCT
GONAD
on hold
WOLFFIAN DUCT
TESTIS
PARAMESONEPHRIC DUCT and
UROGENITAL
SINUS &
MESONEPHRIC
TUBERCLE
DUCT
INTERSTITIAL
CELLS
RETE
EPIDIDYMIS
TESTIS
PROSTATE
PENIS
urethra
DUCTUS
TUBULUS
DEFERNS
RECTUS
EFFERENT
SEMINIFEROUS
DUCT SEMINAL
TUBULE
VESICLE
BULBOURETHRA
L GLAND
Default pathway
GONAD
on hold
Y
OR
GONAD
on hold
OVARY
OVARY
no Y
Sex-determining Factor/SRY
acts on gonad
TESTIS
UROGENITAL SINUS
& TUBERCLE
MULLERIAN DUCT
ParaMesoN
Driven pathway
Testosterone
TESTIS
INTERSTITIAL
CELLS
:
act on Repro ducts
TUBULUS
RECTUS
SEMINIFEROUS
TUBULE
MesoN
Mullerian-inhibiting
Factor
SERTOLI CELL
WOLFFIAN DUCT
Default pathway
GONAD
on hold
:
WOLFFIAN DUCT
regresses
OVARY
MULLERIAN DUCT
GENITAL TUBERCLE etc
OVARY
?
UTERINE
TUBE
UTERUS
VAGINA
VULVA
Mesonephric
REMNANTS IN THE WOMAN
MULLERIAN DUCT
OVARY
:
UTERINE
TUBE
VAGINA
:
Epoophoron &
Paraoophoron
UTERUS
VULVA
:
Gartner’s cyst
WOLFFIAN DUCT regresses, except for
infifferent
GONAD
MALE FACTORS & TARGETS
IN SEXUAL DEVELOPMENT
Y
Sex-determining Factor/SRY
UROGENITAL SINUS
& TUBERCLE
Dihydrotestosterone
TESTIS
TESTIS
WOLFFIAN DUCT
Testosterone
INTERSTITIAL
CELLS
:
TUBULUS
RECTUS
SEMINIFEROUS
TUBULE
:
Mullerian-inhibiting
Factor
SERTOLI CELL
Driven pathways
MULLERIAN DUCT
regresses
DRIVEN PATHWAYS
GONAD
on hold
Y
Mullerianinhibiting Factor
Sex-determining Factor/SRY
MIF
MULLERIAN DUCT
regresses
Testosterone
TESTIS
TESTIS
Dihydrotestosterone
WOLFFIAN DUCT
INTERSTITIAL
CELLS
RETE
EPIDIDYMIS
TESTIS
UROGENITAL SINUS
&TUBERCLE
PROSTATE
PENIS
urethra
DUCTUS
DEFERNS
TUBULUS
RECTUS
EFFERENT
SEMINIFEROUS
DUCT
SEMINAL
TUBULE
VESICLE
BULBOURETHRAL
GLAND
Paramesonephric
REMNANTS IN THE MAN
WOLFFIAN DUCT
TESTIS
INTERSTITIAL
CELLS
RETE
EPIDIDYMIS
TESTIS
UROGENITAL SINUS
&TUBERCLE
PROSTATE
PENIS
urethra
DUCTUS
DEFERNS
TUBULUS
RECTUS
EFFERENT
SEMINIFEROUS
DUCT
SEMINAL
TUBULE
VESICLE
:
Appendix testis
MULLERIAN DUCT regresses, except for
BULBOURETHRAL
GLAND
Prostatic Utricle
VERY LUCKY PROSTATE SECTION
FIBROUS
STROMA
URETHRA
PROSTATE
Ejaculatory duct
P
R
O
S
T
A
T
I
C
Prostatic
URETHRA
UTRICLE
ED
GLANDS
ED
VERUMONTANUM or
Seminal colliculus - the
ridge in the floor of the
prostatic urethra
SOME SEXUAL HOMOLOGUES
OVARY
UTERINE
TUBE
VAGINA
UTERUS
Ovary
:
VULVA
Uterine
tube
Gartner’s
duct
Efferent
ducts
Appendix
testis
Epididymis P Utricle
:
Epoophoron
Testis
TESTIS
INTERSTITIAL
CELLS
RETE
EPIDIDYMIS
TESTIS
Uterus
Clitoris
Penis Scrotum
PROSTATE
PENIS
urethra
DUCTUS
TUBULUS
DEFERNS
RECTUS
EFFERENT
SEMINIFEROUS
DUCT SEMINAL
TUBULE
VESICLE
Labia
majora
BULBOURETHRA
L GLAND
Problems of sexual development can arise at
several points, thus:
(i) Absent or faulty SRY gene in the male
(ii) Failure of testis cells to respond to the gene's product
:
(iii) Absent or defective MIF gene; or problems in the
Mullerian duct's response to MIF
(iv) Leydig-cell failure to make and deploy the enzymes
to produce testosterone
(v) Defective or absent androgen receptor in the Wolffianduct and external-genital targets for testosterone
( XY genotype, but woman’s phenotype)
Problems of sexual
development can arise
at several points, thus:
(ii) Failure of testis cells to
respond to the gene's product
GONAD
on hold
(iv) Leydig-cell
failure to make and
deploy the enzymes
to produce
testosterone
Y
(i) Absent or faulty
SRY gene in the male
Sex-determining Factor/SRY
MIF
MULLERIAN DUCT
regresses
Testosterone
TESTIS
WOLFFIAN DUCT
TESTIS
Mullerianinhibiting Factor
INTERSTITIAL
CELLS
RETE
EPIDIDYMIS
TESTIS
Dihydrotestosterone
UROGENITAL
SINUS &TUBERCLE
PROSTATE
PENIS
urethra
DUCTUS
TUBULUS
DEFERNS
RECTUS EFFERENT
SEMINIFEROUS
DUCT SEMINAL
TUBULE
VESICLE
(iii) Absent or
defective MIF gene;
or problems in the
Mullerian duct's
response to MIF
BULBOURETHRA
L GLAND
(v) Defective or absent androgen receptor in the
Wolffian-duct and external-genital targets for
testosterone ( XY genotype, but woman’s phenotype)
Epiphenomenon
Something happening along with
something else, and perhaps related to it
“An attendant phenomenon appearing with
something else and referred to that as its cause”
- Webster’s Collegiate Dictionary 5th ed 1948
MA & PA MEIOSIS
AIM:
From one 1o spermatocyte to produce four spermatids,
each with:
(i) 23 chromosomes (haploid #);
(ii) each chromosome derived from either Ma or Pa;
(iii) but with bits of Pa’s chromosome replacing some
of Ma’s, and vice versa
Think quartering cuts
M
P
P
{
M
X23
M
P
MA & PA MEIOSIS
M
M
Primary spermatocytes
M
PP
P
DNA
synthesis
3
maternal-paternal
homologue pairing
3
M
{
P
3
3
Each chromosome now a pair
of chromatids held together
by a centromere
maternal & paternal #3 chromosomes
Bivalent for crossing over
of aligned chromatids
DNA excison & ligation @
Maternal 3
M
{
P
FOUR
SPERMATIDS
Meiotic division I
{
{
Paternal 3
Maternal 3
Meiotic division II
Paternal 3
Centromere splitting
Paternal 3
Secondary spermatocytes
Maternal 3
MA & PA MEIOSIS
M
M
M
PP
P
DNA synthesis
3
3
3
3
maternal & paternal #3 chromosomes
Each chromosome now a
pair of chromatids held
together by a centromere
M
{
P
maternal-paternal
homologue pairing
Primary spermatocytes
M
DNA excision & ligation
@
{
P
M
{
P
Bivalent for crossing over
of aligned chromatids
Meiotic division I
{
{
Paternal 3
Maternal 3
Secondary
spermatocytes
@ Site of trouble DNA
exchange disrupts or cuts
out genes
Meiotic division I
{
{
Paternal 3
Meiotic division I
Maternal 3
Secondary
spermatocytes
Random assignment of maternal & paternal
chromosomes (disjunction)*, e.g.,
1
2
3
4
5
6
Paternal
Maternal
Paternal
Paternal
Paternal
Maternal
etc
1
2
3
4
5
6
Maternal
Paternal
Maternal
Maternal
Maternal
Paternal
etc
* Site of trouble Wrong
assignment of chromosomes,
e.g., 2 #21s to one 2o
spermatocyte & none to the
other. Then + one from
oocyte
= Trisomy 21 in
the zygote
Meiotic division II
Secondary
spermatocytes
FOUR
SPERMATIDS
Paternal 3
{
{
Maternal 3
Maternal 3
Meiotic division II
Maternal 3
Centromere splitting
Paternal 3
Paternal 3
Chromatids now
chromosomes
MA & PA MEIOSIS
M
M
Primary spermatocytes
M
M
PP
P
DNA synthesis
maternal-paternal
homologue pairing
3
{
P
3
3
3
Bivalent for crossing over
of aligned chromatids
Each chromosome now a
maternal & paternal pair of chromatids held
#3 chromosomes
together by a centromere
DNA excison & ligation @
M
{
P
FOUR
SPERMATIDS
Meiotic division I
Paternal 3
{
{
Maternal 3
Maternal 3
Meiotic division II
Paternal 3
Centromere splitting
Paternal 3
Secondary spermatocytes
Maternal 3
OOCYTE’S MEIOSIS RESULTS
OOCYTE
Maternal 3
Paternal 3
OR
Maternal 3
Paternal 3
Zp
2nd POLAR BODY
1st POLAR BODY
unity
function
disjunction
disunity
dysfunction
nondisjunction
OVARY SLIDES
Many of our animal slides have several pale glandular
masses - corpora lutea - that have pushed almost all the
follicles to a part of the ovary not in the section.
There are sometimes quite a few primordial (& a few
primary and later) follicles, but the oocytes are shrunken &
distorted.
Sections through antral follicles can miss the oocyte; or
hit the oocyte, but miss the nucleus
Describe the ovarian follicle in terms of how far the
follicular/ granulosa cells have progressed: squamous,
cuboidal, small & round; one layer, two layers,
multilayered; formed an antrum, or not yet; made a very
large antrum, etc.
The large corpus albicans will not be in these small-animal
ovaries
WHERE AM I?
Online Anatomy Module 1
INTRO & TERMS
CELL
EPITHELIUM
CONNECTIVE TISSUE
MUSCLE
NERVOUS SYSTEM
AXIAL SKELETON
APPENDICULAR SKELETON
MUSCLES
EMBRYOLOGY C
Cellular mechanisms
& Malformations
The Approach
W Beresford
To present what cells do, via particular proteins,
to create an embryo - cellular mechanisms
Cells assemble as tissues, which can have their
own collective tissue actions & interactions
These cellular & tissue events can fail for a
multitude of reasons: we can examine and
classify the resulting malformations & defects
Orofacial development offers examples
101EmbryologyFM.ppt
We can try to break down the underlying reasons why
cells misbehave so, & when vulnerability is greatest
As one aspect, one can list known agents of
teratogenesis - the causing of a malformations
Some agents of teratology
Vitamin A & Retinoids
Thalidomide
X-rays & Radiation
Cancer chemotherapy agents
Cortisone
Sex steroids
Rubella virus
Folic-acid & other deficiencies
Ethyl alcohol
A clear subtext: avoid these
when pregnant, or possibly so
Teratology & Genetic defects: General comments 1
To function, we have thousands of protein types, which
are coded for by individual genes, shared out amongst
the chromosomes
Defective genes - altered, missing or misplaced parts,
or on extra chromosomes , etc - result in proteins that
are absent, altered, or with missing (critical?) parts
Such bad-protein problems may prevent the embryo
from living - lethal mutations & lethal losses
Other bad proteins permit development, but the
individual has minor or major impairment to her/his
metabolism - lactose intolerance vs phenylketonuria
Other bad proteins disturb development so that the baby
is born with anatomical defects involving tissues, limbs,
organs, systems - these are the substance of Teratology
The whole sorry story is medical genetics
Teratology & Genetic defects: General comments 2
The many defects in both metabolism and anatomical
structure may show up in combinations, whose patterns
have sometimes long been noticed & named as So-&so’s syndrome
Every month, in journals such as Development &
Mechanisms of Development, researchers report having
stopped a particular protein from working in mice (e.g.,
bad-protein
prevent the picture
embryo
bySuch
knockouts)
with problems
a resultingmay
developmental
from living
- lethal
mutations
& losses
closely
matching
one
of the many
human syndromes
Knowing what the protein does - signals, receives signals,
is a structural component (e.g., of cartilage or bone matrix), etc offers a molecular explanation for the disorder,
but showing how the common agents of teratogenesis act
has not gone quite as well
And the ‘explaining’ has to extend to events at the cell &
tissue levels, as follow here
Teratology & Genetic defects: General comments 3
Development takes place over many months, and some
organs need much more time than others: for instance,
the nervous system is not not even finished at birth
This creates a long period of vulnerability for some
systems - e.g., face, eyes, teeth, genitalia, & brain. [Thus,
many agents & factors cause mental retardation.]
Some processes are more vulnerable to disruption than
others, creating critical periods while a particular
process is under way
The early formation of the body plan and ‘starting’ the
various organs make the embryonic period (first two
months) more critical than the ‘growing’ fetal period
Conversely, some processes occur later, so that certain
agents can only act then , e.g., excess male steroid hormone
masculinizing female external organs
Cell behaviors underlying embryogenesis I
Cell signaling
Cell division
Stem-cell renewal
Cell differentiation
Cell polarization
Cell adhesion
Cell migration
Apoptosis - Cell death
Differential growth
Mesenchymal-epithelial conversion
Digestion of ECM
Tissue fusion
Epithelio-mesenchymal transformation
Branching morphogenesis
Tissue perforation
Canalization
Tissue-to-tissue signaling
Symmetric & asymmetric divisions
Defects in these cellular processes are part of the
basis for malformations of the embryo
Cell behaviors underlying embryogenesis II
Cell division
rapidly increases the number of cells
& the activties that they undertake
First round of division
Second round of division
Third round of division, & so on
Cell differentiation
Unspecialized cell becomes committed to, or
determined for, a particular fate, e.g., smooth muscle
At some stage, the precursor cells stop dividing
Cell behaviors underlying embryogenesis III
Continuity of cell differentiation
Although one can define stages, by the cell’s appearance, contents
(e.g., new proteins) & behavior, the process is far more continuous than
the naming of stages suggests
Stem cells
If all the starting cells became differentiated, and these were then
RENEWAL
lost, there could be no replacement.
Stem cells solve this problem: (i) by
Stem cells
being able to turn into specialized cell
kinds, but (ii) by also being able
to replace/renew themselves
DIFFERENTIATION
Cell behaviors underlying embryogenesis
IV
Symmetric & asymmetric divisions
These divisions produce identical offspring
This division yields differing cells - asymmetric division
Cell behaviors underlying embryogenesis V
Mitotic cleavage plane can affect cell destiny
Cell polarization
Apical/upper surface
Lateral/side surface
Basal/bottomsurface
The cell reacts to its
neighbors and other
influences to acquire a
special shape, different
surfaces, & exact
placement of its contents
Cell behaviors underlying embryogenesis
VI
Cell polarization
takes various forms
A muscle cell is polarized in relation to
a contractile axis or direction
A migrating cell is polarized in relation
to the substrate that it is crawling on,
and the direction in which it is going
LUMEN
Epithelial cells are polarized in relation
to their basal lamina, the lumen, &
each other
BL
Cell behaviors underlying embryogenesis VII
Cell adhesion takes various forms
Muscle cells attach to each other to
synchronise contraction & transmit
force
A migrating cell adheres to, pulls on, &
releases from its substrate
LUMEN
Epithelial cells attach to their basal
lamina, & to each other, by a variety of
junctions
BL
Divorce comes easily: adhesions
are made to be broken
Cell behaviors underlying embryogenesis VIII
Epithelio-mesenchymal transformation/transition
BL
usually prior to migration by the converted cell
Cell behaviors underlying embryogenesis
IX Mesenchymal-epithelial conversion
BL
Occurs normally when:
mesoderm cells form the somites
mesenchymal cells become endothelium to line
the heart & vessels
intermediate mesodermal cells form the kidney
tubules & glomerular epithelia
Cell behaviors underlying embryogenesis X
Cell migration
A migrating cell adheres to, pulls on, &
releases from its substrate. Requires:
Attachment to a substrate/floor
Release of attachment & reattachment
Actin filaments, soluble actin, & actin-minders, to move
Mitochondria & energy sources
Signals for direction, speed, etc
Cell behaviors underlying embryogenesis XI
Apoptosis - Cell death
followed by discreet removal of
the dead cell by macrophages
Digestion of ECM
Digestion of the basal lamina
BL
Remodeling of connective tissue ECM
Cell behaviors underlying embryogenesis XII
You’ve seen one result
Apoptosis - Cell death
Digestion of ECM
Both processes are involved in the loss of the
tadpole’s tail at metamorphosis into a froglet
Cell behaviors underlying embryogenesis XIII
Thus far, we’ve looked at one or two cells, but as cells
multiply they create tissues that act as larger units which
can shape, fuse, interact, etc
Differential growth
Local growth of Mesenchyme &
epithelium produces a bulge
Growth slower here
Bulges are a frequent feature of development
Cell behaviors underlying embryogenesis XIV
Differential growth
Local growth of Mesenchyme &
epithelium produces a bulge
Growth slower here
Although here it looks as though mesenchyme is
driving the excessive growth, both tissues are
collaborating & growing, and ectoderm & endoderm
elsewhere can be the major players, e.g., in the formation
of the nervous system & liver respectively
EXTERNAL/INTERNAL EMBRYO: CNS I
35 days pc
3 brain ‘vesicles’ are subdividing
Mesencephalon
Rhombencephalon
BRAIN
Diencephalon
now four; then Rhombencephalon
divides into Met- & Myel-encephalons
Cephalic flexure/bend
Cervical flexure
start the folding
Telencephalon
Brain ectoderm by
differential growth has
produced brain vesicles,
the cord, and two major
curvatures
SPINAL CORD
Cell behaviors underlying embryogenesis XV
Tissue-to-tissue signaling
Have the notochord signal the overlying ectoderm to take on extra
functions by making a separate tubular structure - the NEURAL TUBE
and the NEURAL CREST
NC
N
C
MESODERM
MESODERM
Reciprocal Mesenchymal-epithelial signaling is very widely used
Cell behaviors underlying embryogenesis XVI
Fusion of processes I
Initially an epithelial fusion
Growth
Cell behaviors underlying embryogenesis XVII
Fusion of processes II
Initially an epithelial fusion
but followed by:
some cell death
breakdown of basal lamina
ingrowth of mesenchyme
some epithelial conversion
to mesenchymal cells
Cell behaviors underlying embryogenesis XVIII
Fusion of processes III
Reconstruction of the line of fusion almost complete
Cell behaviors underlying embryogenesis XIX
Septation - creation of a partition/septum I
Epithelial proliferation
Remodeling of basal lamina
Growth of mesenchyme
Epithelial fusion
Epithelial proliferation
Remodeling of
basal lamina
Growth of mesenchyme
Mesenchymal breakthrough
Cell behaviors underlying embryogenesis XX
Septation - creation of a partition/septum II
Epithelial fusion
Cell behaviors underlying embryogenesis XXII
Septation - creation of a partition/septum III
Two
Mesenchymal
breakthrough
compartments
Cell behaviors underlying embryogenesis XXIII
Septation - creation of a partition/septum IV
One compartment
In practice, septation is often achieved
by having ingrowth proceed from both
sides of the compartment to be divided
Septation produces lung alveoli
>90% of lung alveoli are created by septation after birth, so
this embryonic process is kept running post-natally
One compartment
becomes two, but not
completely separated
Cell behaviors underlying embryogenesis XXIV
Membrane perforation
Cell apoptosis
BL dissolution & remodeling
Branching morphogenesis I
Cell behaviors underlying
embryogenesis XXV
Epithelio-mesenchymal
interactions result in side buds
that grow, then duplicate again,
& again
Eventually producing final working units,
such as lung alveoli or gland secretory units
Branching morphogenesis II
Eventually producing final working units,
such as lung alveoli or gland secretory units
by:
Construction of lumens
Differentiation into
duct & secretory cells
Construction of stromal
elements & vessels from
mesenchyme
Innervation from ANS
Stroma
[ However, the simple alveolar gland shown will
NOT require the branching morphogenesis
needed for compound glands & the lungs ]
Branching morphogenesis III
Selective cell proliferation
& cell polarization
to change the direction of growth
Remodeling of
basal lamina
Branch point
Epithelial proliferation inhibited
ECM firmed up
Digestion of mesenchyme
Branching morphogenesis IV
It gets interesting after just
four generations of branching
The amount of growth before the
change of direction is clearly
critical to making a compact organ
Canalization
Cell behaviors underlying
embryogenesis XXVI
Outgrowth of cells
to produce a cord
Differentiation into
duct/vessel-lining cells
Apoptosis & separation
to hollow out the cord
Endothelial-cell cords can anastomose (join
end-to-end) to create a capillary network
Vessel construction
Endothelial-cell cords can anastomose (join
end-to-end) to create a capillary network
Or surrounding mesenchymal cells can build the connectivetissue and muscle layers of a larger vessel’s wall
ADVENTITIA
INTIMA
MEDIA
Ligamentous conversion
Cell behaviors underlying
embryogenesis XXVII
Almost the opposite of canalization is the taking of a fetal vessel
(or a duct) out of use by converting it to a fibrous cord or ligament
Death of endothelial
& muscle cells
Reinforcement of adventitial
connective tissue
LIGAMENT
E.g., Ligamentum teres of the liver was the left umbilical vein
OROFACIAL MALFORMATIONS : Processes
DYSPLASIA
wrong growth
HYPOPLASIA
too little growth
HYPERPLASIA
too much growth
FUSION FAILURE
SEPARATION FAILURE
PERSISTING PAST TIME
CYST FORMATION
Basis for malformations: Hypoplasia
Too little growth
Failure to grow fully or at all
Instead of
Basis for malformations: Failure to fuse
Growth
One reason
for no fusion
Hypoplasia of one/both processes means that they do
not meet, and therefore they cannot fuse
Adhesion problems could be another reason
CLEFT PALATE
from HYPOPLASIA of
MAXILLARY PROCESS
FACE
FACIAL DEFECTS: Failures of processes to fuse
OBLIQUE FACIAL CLEFT
Maxillary & Nasolateral
MEDIAN CLEFT LIP
Nasomedial & Nasomedial
MEDIAN CLEFT JAW
Mandibular & Mandibular
UNILATERAL
CLEFT LIP
Maxillary & Nasomedial
UNILATERAL MACROSTOMIA
Mandibular & Maxillary
FACE
PALATAL DEFECTS II: Failures to fuse
COMPLETE UNILATERAL
ANTERIOR CLEFT
Palate & Lip
Primary & Lateral palatines
AND
Maxillary & Nasomedial
POSTERIOR CLEFT
PALATE Complete
Can occur independently;
can be partial; anterior cleft
can be bilateral
PALATE
Factors causing cleft lip/palate (failed fusion)
Trisomy 13
Vitamin A & Retinoids Quite common - affect
about 1 in 1000 births
Anticonvulsants
Cortisone?
Fusion of processes II
Initially an epithelial fusion
but followed by:
some cell death
breakdown of basal lamina
ingrowth of mesenchyme
some epithelial conversion
to mesenchymal cells
TONGUE MALFORMATIONS I
ARCH
LATERAL LINGUAL SWELLINGS
Failure of these to fuse
properly causes a DEEP
MEDIAL SULCUS or at
worst a BIFID TONGUE
I
II
III
IV
Overgrowth MACROGLOSSIA
Undergrowth MICROGLOSSIA
“Anatomist! He speak
with forked tongue.”
TONGUE MALFORMATIONS II
Remnant of duct
epithelium forms a
LINGUAL CYST
FORAMEN CECUM
from whence the thyroglossal duct set
out to create the thyroid gland
Part of duct opens
back to foramen “FISTULA”
TONGUE
OROFACIAL MALFORMATIONS II Sources
BRAIN
I II
MECKEL’S SYNDROME &
FRONTO-NASAL DYSPLASIA
Defects from bad brainfrontonasal process interactions
PIERRE-ROBIN SYNDROME &
TREACHER-COLLINS SYNDROME
Include poor neural crest
migration & behavior
Defects from first branchial
arch development
Basis for malformations: Failure to migrate
One of many neural-crest instances
SACRAL
N T
Neural crest cells did not
migrate to the colon to
become the parasympathetic neurons
Result - Parasympathetic ganglion
neurons absent
Condition an enlarged
paralyzed colon
- Hirsprung’s congenital
aganglionic megacolon
Symptom - Newborn’s total constipation
Basis for malformations: Failure to perforate
Membrane persists
Processes
blocked or not
started
Cell apoptosis
BL dissolution & remodeling
The earlier intrusion of
mesenchyme can do this
Failure to perforate
Imperforate anus/Anal atresia
Endodermal tube has started many organs
ESOPHAGUS
TRACHEA&
BRONCHI
(& lungs)
STOMACH
LIVER
INTESTINES
PANCREAS
If this cloacal membrane
persists, later the rectum will
lack an opening
Creating a hole surgically is
easy; ensuring good sphincter
CLOACA
action may not be.
Basis for malformations: Apoptotic failure
Apoptosis - Cell death
Both processes are involved in
the loss of the tadpole’s tail
Digestion of ECM
“& it happened to your tail.”
Apoptotic failure
Occasionally, humans have
a persisting tail
LIVER
INTESTINES
Or webs between the fingers
“Join the Navy, perhaps?”
Basis for malformations: Septation failure
Absent or Incomplete Septation
Lung alveoli insufficiently partioned
One compartment stays
Heart ventricles stay connected
Semilunar valves not formed, etc
Embryology XII
How do the brain & cord form?
How do the brain & cord come to
be enclosed in soft wrappings and
bone?
Is the enclosure sometimes not complete?
Yes - another, but not so rare, malformation
Spinal canal open
Cord exposed
Neural Plate
Events in neural tube formation
Ectodermal Thickening
Neural Groove
Downgrowth
Clefting or
Trough production
Ingrowth
Fusion
Neural
Tube
Separation
Tube production
Many agents of teratology affect the neural tube
Folic-acid & folic acid antagonists
X-rays & Radiation
OPEN
Ethyl alcohol
Vitamin A & Retinoids
CLOSED
OPEN
The open ends are the Neuropores
Failure of the neuropores to close & create a closed fluid-filled
system causes severe CNS defects
Often compounded by a lack of enclosure by the meninges and
spinal/cranial bone
‘SPINA BIFIDA’ varies in severity
BRAIN
The spinal tube has failed to close &
get established - a very severe defect,
HEART
leaking CSF & causing
secondary brain abnormalities
Spinal canal open - bifid
25 d pc
Several names are
used to indicate the
‘openess’ of the cranial
bone/spine, & how
protruding or open are
the meninges
Cord formed properly, but exposed
Monozygotic twins
A felicitous, if expensive, malformation is twinning
Except for placental arrangements, each twin’s development is normal
How is it that I have
an identical twin?
Bill
Ben
BLASTOCYST
INNER CELL MASS
SPLITS INTO TWO The common event
Conjoined/Siamese twins (Monozygotic)
A rare, unhappy outcome A mal malformation
Why are we stuck together?
Bill
Ben
BLASTOCYST
This depicts a relatively
benign chest connection
INNER CELL MASS
did not separate completely
Malformations in particular systems
BRAIN
HEART
25 d pc
For particular organs - heart, brain, lung,
eye, etc - their complicated development
can go astray in many ways.
Some of these events are very rare and
are of more interest for theory than
practice; others, for instance in the heart
& genitourinary systems, are not that
uncommon, and need to be understood
and learned
WHERE AM I?
Online Anatomy Module 1
INTRO & TERMS
CELL
EPITHELIUM
CONNECTIVE TISSUE
You are at the End
Caution how you exit.
BACK on your
browser is needed
Unfortunately there is
no way that you can
NERVOUS SYSTEM
directly reach other
topics listed here by
AXIAL SKELETON
clicking on them. You
APPENDICULAR SKELETON
get there by going back
MUSCLES
to the Paramedical
Anatomy menu
MUSCLE
EMBRYOLOGY C
EXTERNAL EMBRYO II
25 days pc
BRAIN
Anterior NEUROPORE
Tube not fully closed as
brain at a very early stage
BRANCHIAL/PHARYNGEAL
ARCHES starting for face &
neck structures
CARDIAC
BULGE
SOMITES
BODY STALK
Posterior NEUROPORE
bulging under
the ectoderm
EXTERNAL EMBRYO III
35 days pc
LENS PLACODE
for eye
LIMB BUD
UMBILICAL
CORD
CARDIAC
SWELLING
SOMITES
bulging under
the ectoderm
TAIL
part for coccyx;
part for discard
LIMB BUD