COLLEGE OF PUBLIC HEALTH

HEAD & NECK ANATOMY I

SPTH 204

Dr. Raoul Nap

Fall 2018-2019
 COURSE MATERIALS
• Embryology / Histology
• Brain & Brain Development
• Respiratory System
BASIC EMBRYOLOGY
 Follicle Maturation and Ovulation
Oocytes
~2 million at birth
~40,000 at puberty
~400 ovulated over lifetime

Luteinizing Hormone surge

(from pituitary gland)
causes changes in tissues
and within follicle:
• Swelling within follicle due to
increased hyaluronan
• Matrix metalloproteinases
degrade surrounding tissue
causing rupture of follicle

Egg and surrounding cells

(corona radiata) ejected into
peritoneum
Corona radiata provides bulk to
facilitate capture of egg.
THE EGG (AND CORONA RADIATA) AT OVULATION

Corona radiata
Zona pellucida
(ZP-1, -2, and -3)
Cortical granules
TRANSPORT THROUGH THE OVIDUCT
At around the midpoint of the
menstrual cycle (~day 14), a
single egg is ovulated and
swept into the oviduct.
Fertilization usually occurs in
the ampulla of the oviduct
within 24 hrs. of ovulation.
Series of cleavage and
differentiation events results in
the formation of a blastocyst
by the 4th embryonic day.
Inner cell mass generates
embryonic tissues
Outer trophectoderm
generates placental tissues
Implantation into the uterine
wall occurs ~6th embryonic day
(day 20 of the menstrual cycle)
 Timing of
pregnancy

Embryologists Clinicians
Fertilization age: moment of fertilization is dO Menstrual age: last menses is dO
Division of pregnancy corresponding to development: Division of pregnancy into trimesters
0-3 weeks –early development Total gestation time = 40 weeks
3-8 weeks –embryonic period (organogenesis)
8 wks-term –fetal period
Total gestation time = 38 weeks
Fertilization is a multi-step process whereby multiple sperm bind to the
corona radiata, but only a single sperm usually fertilizes the egg

1. ACROSOME RX
SPERM BIND TO ZP
PROTEINS IN THE ZONA
PELLUCIDA; THIS
INITIATES THE RELEASE OF
ENZYMES FROM THE
SPERM ALLOWING IT TO
BURROW THROUGH THE
ZONA PELLUCIDA.

2. ZONA RX
BINDING OF THE SPERM
AND EGG PLASMA
MEMBRANES INITIATES
CA+ INFLUX INTO THE EGG
AND RELEASE OF
CORTICAL GRANULES
FROM THE EGG THAT
BLOCK OTHER SPERM
FROM FERTILIZING THE
EGG.
This so-called cortical reaction prevents other sperm
from fertilizing the egg (aka “polyspermy”)

Cortical granule
enzymes digest ZP
proteins so other sperm
can no longer bind.

Hyaluronic acid and

other proteoglycans are
also released that
become hydrated and
swell, thus pushing the
other sperm away.
FERTILIZATION
Meiosis II complete

Formation of male and

female pronuclei

Decondensation of male
chromosomes

Fusion of pronuclei

Zygote
WEEK 1: DAYS 1-6
• Fertilization, day 1
• Cleavage, day 2-3
• Compaction, day 3
• Formation of blastocyst, day 4
• Ends with implantation, day 6
Fertilized egg (zygote)

Fertilized egg
2 polar bodies
2 pronuclei

Day 1
0.1 mm
CLEAVAGE
Cleavage = cell division

Goals: grow unicellular

zygote to multicellular embryo.
Divisions are slow: 12 - 24h ea
No growth of the embryo-
stays at ~100 um in diameter
Divisions are not synchronous

Cleavage begins about 24h after

pronuclear fusion
2 CELL STAGE

Individual cells = blastomeres

Mitotic divisions maintain

2N (diploid) complement

Cells become smaller

Blastomeres are equivalent (aka totipotent).

4 CELL; SECOND CLEAVAGE

4 equivalent blastomeres

Still in zona pellucida

8 CELL;
THIRD
CLEAVA
GE
BLASTOMERES
STILL
EQUIVALENT
EMBRYO UNDERGOES COMPACTION AFTER 8-CELL STAGE:
FIRST DIFFERENTIATION OF EMBRYONIC LINEAGES

Caused by increased cell-cell adhesion

Cells that are forced to the outside of the morula are destined
to become trophoblast--cells that will form placenta
The inner cells will form the embryo proper and are called
the inner cell mass (ICM).
 FORMATION OF THE
BLASTOCYST

Sodium channels appear on the surface of the outer trophoblast cells;

sodium and water are pumped into the forming blastocoele. Note that
the embryo is still contained in the zona pellucida.
Early blastocyst Later blastocyst
Day 3 Day 5

inner cell mass

blastocoele
 MONOZYGOTIC TWINNING TYPICALLY
OCCURS DURING CLEAVAGE/BLASTOCYST
STAGES
“HATCHING” OF THE BLASTOCYST:
PREPARATION FOR IMPLANTATION

Hatching of the embryo from the zona pellucida occurs just

prior to implantation. Occasionally, the inability to hatch
results in infertility, and premature hatching can result in abnormal
implantation in the uterine tube.
ECTOPIC
IMPLANTATION
Implantation somewhere
other than upper portion
of uterus

“Rupture” can lead to life-

threatening hemorrhage
TUBAL PREGNANCY
WEEK 2: DAYS 7-14
IMPLANTATION
• Implanted embryo becomes more deeply
embedded in endometrium

• Further development of trophoblast into placenta

• Development of a bi-laminar embryo, amniotic

cavity, and yolk sac.
IMPLANTATION AND PLACENTATION (DAY 8)

Trophoblast further differentiates and invades maternal tissues

– Cytotrophoblast: stem cell population
– Syncytiotrophoblast: invasive fused cells (syncytium) derived from cytotrophoblast
– Breaks maternal capillaries, trophoblastic lacunae fill with maternal blood
Inner cell mass divides into epiblast and hypoblast:
– Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity
– Hypoblast contributes to forming the underlying yolk sac.
IMPLANTATION AND PLACENTATION (DAY 9)

Trophoblast further differentiates and invades maternal tissues

– Cytotrophoblast: stem cell population
– Syncytiotrophoblast: invasive fused cells (syncytium) derived from cytotrophoblast
– Breaks maternal capillaries, trophoblastic lacunae fill with maternal blood
Inner cell mass divides into epiblast and hypoblast:
– Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity
– Hypoblast contributes to forming the underlying yolk sac.
IMPLANTATION AND PLACENTATION (DAY 12)

Trophoblast further differentiates and invades maternal tissues

– Cytotrophoblast: stem cell population
– Syncytiotrophoblast: invasive fused cells (syncytium) derived from cytotrophoblast
– Breaks maternal capillaries, trophoblastic lacunae fill with maternal blood
Inner cell mass divides into epiblast and hypoblast:
– Epiblast contributes to forming the overlying amniotic membrane and amniotic cavity
– Hypoblast contributes to forming the underlying yolk sac.
IMPLANTATION AND PLACENTATION (DAY 13)

Trophoblast further
differentiates and invades
maternal tissues
– Cytotrophoblast: stem cell
population
– Syncytiotrophoblast: invasive
fused cells (syncytium) derived
from cytotrophoblast
– Breaks maternal capillaries,
trophoblastic lacunae fill with
maternal blood
Inner cell mass divides into
epiblast and hypoblast:
– Epiblast contributes to forming
the overlying amniotic
membrane and amniotic cavity
– Hypoblast contributes to
forming the underlying yolk sac.
WEEK 3: DAYS 14-21

• Two layer germ disc

• Primitive streak forms
• Gastrulation forms tri-laminar embryo
• Neural induction
• Left-right asymmetry
• 0.4mm - 2.0mm
GASTRULATION
At gastrulation the two layered epiblast is converted
into the three primary embryonic germ layers:

– Ectoderm: outside, surrounds other layers later in

development, generates skin and nervous tissue
– Mesoderm: middle layer, generates most of the muscle,
blood and connective tissues of the body and placenta
– Endoderm: eventually most interior of embryo,
generates the epithelial lining and associated glands of
the gut, lung, and urogenital tracts
THE HUMAN EMBRYO AT GASTRULATION
AT GASTRULATION, PRIMITIVE ENDODERM IS
REPLACED BY DEFINITIVE OR EMBRYONIC
ENDODERM THEN MESODERM IS FORMED
CELL MOVEMENTS DURING GASTRULATION
Mesoderm is patterned in a cranial to caudal gradient
Axial mesoderm: passes
through the node and migrates along
the midline –forms the notochord

Paraxial mesoderm: passes

just caudal to the node and migrates
slightly laterally –forms cartilage,
skeletal muscle, and dermis

Lateral plate mesoderm:

passes more caudal and migrates
more laterally –forms circulatory
system and body cavity linings.

Extraembryonic mesoderm:
passes most caudal and migrates
most laterally –forms extraembryonic
membranes and associated
connective tissue & blood vessels.
 Fate of the “axial” mesoderm
The notochord and pre-chordal plate develops from mesoderm arising from cells that passed
directly through the node and migrated cranially along the midline
The notochord and pre-chordal plate are important signaling centers that pattern the
overlying ectoderm and underlying endoderm.
 MAJOR SIGNALING CENTERS AT GASTRULATION:
THE NODE AND THE ANTERIOR VISCERAL ENDODERM (AVE)

• Primitive node positions primitive streak for gastrulation, induces neural differentiation

• AVE from primitive endoderm secretes factors that position primitive streak in posterior, induce head
formation
THE NODE ALSO SETS UP THE NEURAL PLATE
 Head signaling centers

Prechordal plate~ early notochord

LEFT-RIGHT ASYMMETRY IS
ESTABLISHED AT GASTRULATION
Leftward beating of cilia at node moves
secreted molecules sonic hedgehog (Shh)
& FGF-8 to the left side of embryo.

Causes left side genes Nodal and Pitx2 to

be expressed which then pattern
developing organs.

If cilia are defective, Shh and Fgf8 can

randomly end up on right side, resulting in
reversal of symmetry, aka situs inversus
(liver on the left, spleen on the right, etc.)

Situs can be complete (everything

reversed) or partial (only some organs
reversed).
SITUS INVERSUS