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EMBRIOLOGI SISTEM SARAF DAN

MUSCULOSKELETAL

Dr. Zainuri Sabta N


Departemen Anatomi FK UII
Embryology
Definisi: studi tentang asal-usul dan
perkembangan suatu organisme
Periode Prenatal : sebelum lahir
38 minggu dari pembuahan sampai usia lahir (rata-
rata) "janin"
Waktu ginekologi setelah HPM; karena itu mengacu
pada usia 40 minggu "kehamilan"
TAHAPAN PERKEMBANGAN EMBRIO-
JANIN
(berdasarkan urutan waktu)
Week 9 to birth
Fetal development: overall growth, maturation of tissues

Resumme
Week 1-2: formation of zygote, implantation and
formation of bilaminar embryo
Weeks 3-8: Embryological period
Weeks 9-38: Fetal period
Embryogenesis
Menurut Dorlands Illustrated Medical Dictionary,
Embriogenesis adalah :
1. produksi dari embrio;
2. perkembangan dari individu yang baru yang terjadi
secara seksual yaitu dari zigot.
Embriogenesis adalah proses pembelahan sel dan
diferensiasi sel dari embrio manusia yang terjadi pada
saat tahap-tahap awal dari perkembangan manusia
tepatnya sejak fertilisasi sampai akhir dari minggu ke-8
dari perkembangan manusia (Langman,1994).
Traditional (artificial) division:

Periode Embryonic : 8 minggu awal


kehamilan
Semua organ utama
Periode embrio dianggap waktu yang paling kritis dalam
perkembangan manusia dari induksi cacat lahir. paling sensitif
terhadap penghinaan teratogenik.
Periode Fetal : 30 minggu sisa kehamilan
(sampai lahir)
Organ tumbuh lebih besar dan menjadi lebih kompleks
Fertilization (first week)
Penetration of Zona Pellucida
Once inside the corona radiata, the sperm binds to the species-
specific ZP3 receptor on the eggs glycoprotein coat. This triggers
the acrosomal reaction, or the release of enzymes stored in the
sperms acrosome (e.g. acrosin). These enzymes help the sperm
drill through the zona pellucida
Once the sperm has
penetrated the outer layers it
fuses with the plasma
membrane of the egg and
releases its contents inside.
The head and the tail of the
sperm degrade, so that all
mitochondria in the
embryo (and all
mitochondrial DNA) come
from the mother.
Fertilization (first week)
Cortical Reaction
During ovulation oocyte
completes meiosis I, stops in
metaphase of meiosis II
Fusion of oocyte and sperm
membranes triggers -- oocyte
completes meiosis II
Afterwards the male and female
pronuclei fuse and the egg
completes its second meiotic
division, resulting in a second
polar body. The fertilized egg
is now known as the zygote
(together).
The 23 chromosomes of the
sperm join with the 23
chromosomes of the egg to
restore the diploidnumber of 46
in the zygote.
A zygote has 22 pairs of
autosomes and one pair of sex
chromosomes; XX in females,
XY in males.
Ovulation: egg released into the peritoneal
cavity
Travels down fallopian tube in which
fertilization occurs
At conception in fallopian tube, maternal and
paternal genetic material join to form a new
human life (zygote)
Cell division occurs with travel down the tube
and into the uterus

Conception (biology) or fertilisation, the fusion of gametes to


produce a new organism of the same species (Wikipedia)
Week 1 post conception

Zigot membelah berulang kali bergerak turun menuju


uterus (Cleavages)
Sel anak disebut blastomer
Morula: cluster padat terdiri dari 12-16 blastomer
(terbentuk sekitar 72 jam)
Hari 4: akhir 60 sel morula memasuki uterus,
mengandung cairan menjadi blastokista
Cleavage (membelah)
At the 32-cell stage the embryo is known as a morula (L.
mulberry), a solid ball consisting of an inner cell mass and
an outer cell mass. The inner cell mass will eventually
become the embryo and fetus, while the outer cell mass
will eventually become part of the placenta.
Blastocyst stage
_____inner cell mass

______trophoblast
Two distinct types of cells
Inner cell mass: forms the embryo
Trophoblast: layer of cells surrounding the cavity which
helps form the placenta
Floats for about 3 days
Implantation on about day 6 post conception
Trophoblast erodes uterine wall
Takes 1 week to complete
If inner cell mass of a single blastocyst divides:
monozygotic (identical) twins
Implantation
Implantation 5 to 8 days after fertilization

The zona pellucida must degenerate for


implantation to occur.
One function of the zona pellucida is to
prevent premature implantation.

Attachment and Invasion


The embryo attaches to and invades into
the maternal endometrium.
The trophoblast differentiates into the
cytotrophoblast and the
syncytiotrophoblast.
The embryo typically implants in the
posterior superior wall of the uterus.
The response of the maternal
endrometrial cells to the invading embryo
is called the decidual reaction.
Implantasi lengkap
terjadi pada minggu
ke 14 kehamilan.
Week 2:
Trophoblast consists of two layers = cytotrophoblast (makes cells),
syncytiotrophoblast = invasion and hormones.
Inner cell mass = germ disc = two layers: epiblast and hypoblast.
Two cavities: amniotic = dorsal to epiblast; yolk sac = ventral to
hypoblast.
Extraembryonic mesoderm formed around the amniotic and yolk
sac cavities = splits into two layers = somatic and splanchnic. Cavity
between = chorionic cavity.
Two layers of extraembryonic mesoderm connected at connecting
stalk (umbilical region).
At about 12-14 days, the embryo penetrates uterine vessels =
some bleeding = may misdiagnose as menstrual bleeding =
misdiagnose pregnancy and age of embryo.
Ectopic pregnancy = ampullary region = most common.
Rectouterine (Douglas) pouch = most common in abdomen.

Week 2 - week of 2s:


2 layers to trophoblast: syncytiotrophoblast and cytotrophoblast
2 layers to embryoblast: epiblast and hypoblast
2 cavities: amniotic and yolk sac
2 layers of extraembryonic mesoderm: somatic and splanchnic
Embryology The BI-LAMINAR embryo

Back at this stage, the two layers constituted


the BI-LAMINAR embryo

EPIBLAST

HYPOBLAST

The TRI-LAMINAR embryo

ECTODERM

MESODERM In side view

ENDODERM
MESENCHYM
Embryology 6-d BLASTOCYST

Directions of growth
EPIBLAST will sort itself into a single layer
for the EMBRYO, & an overlying
AMNIOTIC cover

HYPOBLAST
will form the YOLK SAC

CYTOTROPHOBLAST
about to invade the uterine mucosa &
eventually form the PLACENTA
Embryology The three GERM LAYERS
The blast suffix is still here being used to indicate formative power,
as is the term germ layer for what derives from the epiblast

EPIBLAST EPIBLAST forms


three layers

(HYPOBLAST)

ECTODERM

MESODERM

Note - Mesoderm is the middle layer ENDODERM


Week 3 = week of 3s:

Week 3: 3 germ layers: ectoderm, mesoderm, endoderm


3 cavities: amniotic, yolk sac, chorionic
Gastrulation = process of making three germ layers: ectoderm
(skin, CNS), mesoderm (blood, bones, connective tissue), and
endoderm (gut, parenchyma of glands).
Epiblast = forms all three germ layers = all of the embryo.
Hypoblast disappears.
Primitive streak forms at the caudal end of embryo at the beginning
of the third week = cell migration from epiblast to form germ
layers. Node = organizer = cranial end of streak = notochord cells.
Notochord = induces CNS, forms nucleus pulposus in
intervertebral discs.
Trophoblast = forms villi for placenta = vessels formed in
extraembryonic mesoderm connect to umbilical vessels = fetal
circulation
Embryology
The tri-laminar embryo acquires depth by cell
division, ECM-production, and directional growth

ECTODERM

MESODERM

ENDODERM

The endoderm, working to a tighter radius, comes


around to meet itself & make an inner tube
The ectoderm, working to a wide radius, comes
around to meet itself & make a covering
The mesoderm fills the space in between
MESENCHYM
TAHAPAN PERKEMBANGAN EMBRIO-
JANIN
(berdasarkan urutan waktu)
Week 4
Neurulation: neural plate, neural folds, neural plates; proceeds
middle to ends
Neural crest cells form
Paraxial, intermediate, and lateral plate mesoderm can be
distinguished
Paraxial mesoderm forms somites, cranial to caudal direction;
somites differentiate into dermo-, myo-, and sclerotome parts
Intermediate mesoderm begins to form mesonephros (ginjal)
Lateral plate mesoderm gives rise to somatic and splanchnic
mesoderm, intraembryonic coelom forms
Folding laterally and craniocaudally, which is also important to GI
development
Through Week 8, embryogenesis of all major organ systems
Neurulation
Notochord signals overlying ectoderm
Formation begins of spinal cord and brain (neurulation)
Neural plate to neural groove to neural tube: pinched off into
body
Closure of neural tube: begins at end of week 3; complete by
end of week 4 (folic acid important for this step)
Extends cranially (eventually brain) and caudally (spinal cord)
Neural crest, lateral ectodermal cells, pulled along and form
sensory nerve cells and other structures
Mesoderm begins to differentiate
Lateral to notochord, week 3
Extends cranially and caudally (from head to tail or crown
to rump)
Division of mesoderm into three regions
Somites: 40 pairs of body segments (repeating units, like
building blocks) by end week 4
Intermediate mesoderm: just lateral to somites
Lateral plate: splits to form coelom (cavity)
Major derivatives of the embryonic germ layers
Trilaminar:
minggu ke tiga embrional
Embryology MESODERM
the middle layer
E C T O D E R M

E N D O O D E R M

MESENCHYME Mesoderm cells quickly


separate themselves by
making extracellular
matrix (ECM)
Some mesoderm thus
becomes
Mesenchyme - the
forerunner of
connective tissues
Embryology Germ-layer origins of tissues
are primary concerns of embryology

Epithelium ENDODERM
GI & respiratory

Connective
tissue

Smooth muscle MESODERM

In general

Nervous tissue
In general ECTODERM
ECTODERM
Embryology

MESODERM
ENDODERM
Resulting tubular/ cylindrical form

ECTODERM

MESODERM

ENDODERM
Embryology
In sagittal view, the resulting structure has the makings of a little
animal, but Wheres my head?

For starters, have the ECTODERM


invaginate in at one end
& interact with local mesenchyme
to form a mouth

MESODERM
Embryology In sagittal view, the resulting structure has
the makings of a little animal, but
Wheres my head?
Also, have the ECTODERMAL NEURAL TUBE grow more
at the rostral/cephalic end for the big brain

TUBE
NEURAL FOLDS OPEN CLOSED OPEN

View looking down from the amnion


side onto the dorsal embryo

MESODERM
Embryology
In sagittal view, the resulting structure has the makings of a little
animal, but Im going to be complex: wheres my coordinating system
Wheres my brain & nervous system?
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
Have the notochord signal the
overlying ectoderm to take on extra
functions by making a separate tubular
structure - the neural tube
MESODERM

N T

NC

Ectodermal formation of the tube requires many steps


Neural Plate
Events in neural tube formation
Neurulation is the whole process
Ectodermal Thickening
Neural Groove Downgrowth
Clefting or
Trough production

Ingrowth

Fusion

Neural Tube

Separation

Tube production
Events in neural crest formation

Ectodermal Thickening

Specialization in the
lateral neural plate

Separation from ectoderm


AND the forming neural
tube

Change of crest cells to a


migratory nature/phenotype

Cells start moving, partly by


their own program, & partly
in response to cues
Neural tube closure
Fusion (closure) of the neural tube starts centrally
and proceeds in both directions- rostrally & caudally
OPEN NEURAL GROOVE

OPEN CLOSED

View looking down from the amnion


side onto the dorsal embryo
NEURAL FOLDS

Fusion Ingrowth
Ingrowth

Neural Tube
Neural tube closure
Ingrowth
Fusion

Neural Tube

Fusion (closure) of the neural tube starts centrally


and proceeds in both directions- rostrally & caudally

OPEN CLOSED OPEN

The open ends are the Neuropores


Neural crest fates I

Neural-crest cells establish*


the peripheral nervous system:
ganglia, nerves, receptors

Sensory neurons Receptor cells, e.g.,


Merkel cells, Carotid
Autonomic neurons body cells

Satellite cells
* Note: Motor neurons & their
Schwann cells
axons are neural-TUBE derivatives
Neural crest fates I

Neural-crest cells establish*


the peripheral nervous system:
ganglia, nerves, receptors

Sensory neurons Receptor cells, e.g.,


Merkel cells, Carotid
Autonomic neurons body cells

Satellite cells
* Note: Autonomic Motor neurons &
Schwann cells
their axons are neural-TUBE derivatives
Neural crest fates II

NC cells also give rise to other


cell types & tissues of the:
skin, glands, heart & the head

Melanocytes/Pigment cells

Adrenal medulla Vault & Face bone &


chromaffin cells cartilage cells
Thyroid C cells Facial fibroblasts
Neuroendocrine cells
Tooth dentine & pulp
Partitions & outflow Eye & facial smooth
region of heart muscle cells
Partial listing
Embryology
Somites are not at the far head OPEN
end, because the head gets its
mesenchyme from neural crest 1

The somites are covered with C SOMITES


ectoderm (not shown), with L
O
which part of the somite will S
later interact E
D 7

Remember 7-12-5-5-4
vertebrae. Many more
somites than 7 need to be
N
OPE
recruited & some use will be
abortive
Embryology
In sagittal view, the resulting structure has the makings of a little
animal, but Im going to grow, so how will I fit into Mom?
Curl up & live OR Love that fetal position

2nd folding of the embryo is not even, but is marked at


the head and the tail, with the cephalad/head fold greater
than the caudal/tail

2nd Folding of the embryo


BRAIN SUB-DIVISIONS
Much more folding of the developing neural tube is
needed to make the brain this compact; the spinal cord
need only follow the mild curvatures of the spine

Cerebral cortex = two


cerebral hemispheres

Cerebellum

Brain stem
Small, on midline, deep &
mostly within brain
(spinal cord)
EXTERNAL/INTERNAL EMBRYO: CNS I 35 days pc
Mesencephalon 3 brain vesicles are subdividing
Rhombencephalon now four, then Rhombencephalon
divides into Met- & Mel-encephalons
BRAIN
Cephalic flexure/bend
Diencephalon
Cervical flexure
start the folding

Telencephalon SPINAL CORD


EXTERNAL/INTERNAL EMBRYO: CNS II 35 days pc

Brain vesicles & cord are hollow

Now neural tube is closed, it


has internal spaces to become
the brains ventricles & the
cords tiny central canal, filled
S
P with cerebrospinal fluid
I
BRAIN N
A The fluid must still drain out of
L small holes, developing later at
C the rear of the brain, to avoid
O
R excess pressure
D
Unbalanced CSF pressure
causes severe malformations

Caudalmost spinal cord will regress


Neural crest for autonomic nervous system
My guts need nervous sensation & control Example
Neural crest cells
migrate to the colon to
SACRAL become the para-
N T sympathetic neurons of
the plexuses
[Only one aspect - its a
complicated system with
sympathetics & centrally
(tube-) derived
preganglionic
cells, & centers]
Embryology
How do muscles, bones, tendons, etc, develop
together as connected working units?
FEMUR
How do the muscles (& controlled by
skin) get a nerve supply? Tibial nerve

TIBIA

FIBULA

Gastrocnemius m
Thus, the
MEDIAN NERVE Soleus m
runs along in
the middle of Achilles Tendon
the forearm

TALUS
CALCANEU
S
Embryology
In sagittal view, the resulting structure has the makings of a little
animal, but
my limbs & body wall need
nervous sensation & control
NEURAL CREST &
TUBE
NC
Have mesodermal cells get
organized close to the neural
tube & crest, so that they can
take their nerves with them as
they grow out & become
MESODERM muscle, etc
Embryology

How close is the relation between the repeating pattern


of vertebrae & ribs along the human body axis and the
body segments that characterize centipedes, etc ?
EXTERNAL EMBRYO 35 days pc

LIMB BUD

CARDIAC
SWELLING
SOMITES
bulging under
the ectoderm

LIMB BUD
OPEN

1
S You remember building with blocks?
O
M C
L Youd done it earlier
I O
S than you realised
T E
E D 7
S
OPEN

At this embryonic stage the


somite for the T2 vertebral
segment has not yet formed
Embryology
OPEN

Somitic mesoderm 1 S
O
C M
L IT
O
S E
E S
D 7

NC

N
OPE
Embryology Roles of mesoderm 6

LATERAL

SOMATIC
NC

SPLANCHNIC

Somatic layer of lateral mesoderm


becomes a DERMOMYTOME

Skins dermis Skeletal muscles


EXTERNAL EMBRYO III 35 days pc

LENS PLACODE
for eye

LIMB BUD
UMBILICAL
CORD
CARDIAC
SWELLING
SOMITES
bulging under
the ectoderm
TAIL
some for coccyx;
some for discard
LIMB BUD
Embryology

Division of Dermatomyotome into

Dermatome

N T

NC

Vertebral body

Myotome
Embryology

N T

NC

Myotome
will separate into Epimere & Hypomere

Dermatomal cells
becoming dermal fibroblasts, etc
Embryology

N T
Dermatome
sends in pre-
NC
dermal
mesenchymal
cells

Myotome
Ventrolateral cells of the myotome become
mesenchymal & migrate into the bud
Other mesodermal cells centrally become
pre-cartilage mesenchymal cells
LIMB BUD
Yet other mesodermal cells provide mesenchyme for
tendons, ligamanents, capsules, etc
Embryology Is it all a mesodermal-
mesenchymal story?
No
N T

LIMB BUD
Motor neuron axons grow from the
neural tube to innervate the muscle

Neural-crest cells form: sensory neurons for


limb proprioception and cutaneous sensation;
autonomic innervation to limb vessels; ganglia,
Schwann cells, receptors, & melanocytes

Apical ectoderm helps control mesenchymal events


Embryology Sensory innervation

N T

LIMB BUD
Motor neuron axons grow from the
neural tube to innervate the muscle

Neural-crest cells sensory neurons (& ganglia)


for limb proprioception and cutaneous
sensation
Embryology Limb development: Sensory nerves

SHOULDER
GIRDLE

Motor neuron axons grow from the


neural tube to innervate the muscle
muscle mass

Neural-crest cells sensory neurons (& ganglia) for limb


proprioception and cutaneous sensation
Embryology Limb development: Muscles
Vertebra & Rib from sclerotome
Skeletal core

Dorsal extensor
muscle mass
SHOULDER
GIRDLE

Epaxial & hypaxial muscle Ventral flexor muscle mass


(shown on one side only)
Muscle masses will later split
into definitive muscles
Embryology Limb development: Skeleton
Skeletal core
Proximal bones form
before distal ones

SHOULDER
GIRDLE Bones are first
pieces of cartilage

Ulna & Radius will split


from one primordium

More wrist-bone primordia will appear,


followed by ones for the digits
Embryology Limb development: Rotations
The developing limb will rotate
forward towards the midline

A further rotation occurs at


the elbow & knee, but in
SHOULDER
opposite directions
GIRDLE

These rotations take with them the nerves innervating the muscles & skin

Resulting in the perplexing pattern of dermatomes in limbs skin

Dermatome here has a different meaning to the somite component


Embryology Tissues of limb & body wall
Roles of mesoderm to form everything but ectodermal
Epidermis
Articular cartilage Dermis

Marrow
Hypodermis
Bone

Joint capsule
Ligament &
Periosteum
Tendon Muscle
SKIN ORIGINS

Meissners ECTODERM

capillary
loop
corpuscle

} EPIDERMIS
Sweat gland
Etc
Mesodermal
DERMATOME

} DERMIS

Pacinian
corpuscle }
Fat cells
HYPODERMIS

NERVE FIBERS & RECEPTORS Neural crest ECTODERM


3 Mesoderm for body wall & limbs Embryology

EPAXIAL
Skin
Dermatome
Rib
for dermis Vertebra

LIMB Cross-section of thorax

HYPAXIAL
Skin
Embryology

N T

NC

Myotome
will separate into Epimere & Hypomere

Why separate the muscle


precursors?
3 Mesoderm for body wall & limbs Embryology
The spine & spinal cord are set very
asymmetrically, way off center
Dorsal
creating special territories
EPAXIAL
Skin

Rib

Vertebra

LIMB
Cross-section of thorax HYPAXIAL

Ventral
3 Mesoderm for body wall & limbs Embryology
DERMOMYOTOME
Dermatome

Myotome
EPAXIAL
Skin

Rib

Vertebra

LIMB
Cross-section of thorax HYPAXIAL
3 Mesoderm for body wall & limbs Embryology

Epimeric
EPAXIAL Myotome
Skin
Dermatome Hypomeric
for dermis
Rib
Myotome
Vertebra

LIMB Cross-section of thorax

HYPAXIAL
3 Mesoderm for body wall & limbs Embryology

Epimeric
EPAXIAL Myotome
Skin
Hypomeric
Rib
Myotome
Vertebra

splits to give the


LIMB Cross-section of thorax layers of
thoracic- &
abdominal-wall
muscle
HYPAXIAL
SPINAL MUSCLES : Erector spinae innervation
Skin
The spinal nerve leaving Posterior
the vertebral canal Dorsal
sends a major branch Rib

(ramus) forward to Vertebra

serve the chest wall -


the ventral ramus The spine & spinal cord are
set very asymmetrically, way
The spinal nerve off center. One consequence:
leaving the vertebral
canal sends a small The bulk of the body served
branch (ramus) by the cord at this level lies
back to serve the ventrally to the front of it
Central-back strip of
skin & the Erector
spinae muscles - the
dorsal ramus Anterior
Ventral
Embryology
Served by Ventral ramus innervation
Skin
DORSAL ramus

Rib

Vertebra
serving

Layers of
thoracic- &
abdominal-wall
muscle

and

Skin
C8 C7 C6 C5 C2
C3
C4

T1
T6
DERMATOME MAN

T12
L1 L2 L3
L4 L5
Speaking of skin, why
does Dermatome
S1 Man have all these
Dermatome here has a colored & numbered
different meaning to the stripes on him?
somite component
Embryology DERMATOMES
Served by
DORSAL ramus Skin
T4 SPINAL NERVES C5
innervate this T4
strip of skin
Rib

Vertebra

T4
Ventral ramus innervation

L5
SPINAL MUSCLES III: Erector spinae innervation I
Skin Posterior
Dorsal
Rib

Vertebra

Cross-section of thorax

The spine & spinal cord are


set very asymmetrically, way
off center.

Anterior
Ventral
SPINAL CORD-NERVE-LIMB RELATIONS
The direct connectors to the spinal C1
cord are the Spinal nerves C1 C2
named in reference C2
to the Vertebrae C3
C3 C4
between which the spinal
nerves exit, via the C4
intervertebral foramina C5
C5
C6
C6
C7

C7 C8
Upper spinal cord

T1 T1
SPINAL CORD-LIMB RELATIONS
C8 C7 C6 C5 C2
Spinal nerves
C3
T1 C4

SN C5 C4
C5

SN C6 C5
Upper Limb C6
Dermatomes
SN C7 C6
C7

C7 C8
SN C8

SN T1 T1 T1
named in reference to the Vertebrae
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