LECTURE NOTE

ANA 221

GASTRULATION,
NEURULATION, FOLDING AND
NEURAL TUBE DEFECT

UCHEWA O. OBINNA
LECTURE NOTE ON EMBRYOLOGICAL
MECHANICS AND TERATOLOGY

ANA 431

BY

UCHEWA O. OBINNA

MAY, 2021
03/06/2023 2
OBJECTIVES
By the end of this lecture , the student should be able to:
 Define Gastrulation

 Describe the formation of the primitive streak

 Describe the formation of the intraembryonic mesoderm

and the Trilaminar disc
 Explain the formation , function and fate of the
notochord
 Define Neurulation

 Describe the formation of the neural plate, groove, fold ,

crest and canal
 Understand the process of folding its timing and results
oGastrulation is a phase early in the embryonic development
of most animals during which the single-layered blastula is
reorganized into a trilaminar (three-layered) structure known
as the gastrula.

oThese three germ layers are known as the ectoderm,

mesoderm, and endoderm.

oGastrulation:is the process of formation of the 3 germ layers

(ectoderm, mesoderm & endoderm).

oAll these significant event happens within the third week of

intrauterine life.
GASTRULATION
 The process by which the bilaminar disc is
converted into a trilaminar disc

 Itis the beginning of morphogenesis (formation

of body form)

 Consists of formation of the primitive streak, the

three germ layers & the notochord

 Embryo is referred to as a Gastrula

 GASTRULATION
 Gastrulation takes place after cleavage and the
formation of the blastula.

 Formation of the primitive streak is the

beginning of gastrulation.

 It is followed by organogenesis—when
individual organs develop within the newly-
formed germ layers.
 PRIMITIVE STREAK
 The primitive streak results from
proliferation of the epiblastic cells
in the median plane, in the caudal
half of the epiblast, and lies along
the cranio-caudal axis.

 Its cranial end forms the primitive

node

 A groove, primitive groove,

appears in the primitive streak,
which continues with a small
depression, primitive pit, in the
primitive node.
A circular thickening appears
in the epiblast near the cranial
end, in the midline, to form the
prechordal plate
( oropharyngeal membrane),
that marks the future site of
mouth

A circular thickening appears

in the hypoblast caudal to
primitive streak in the midline
to form the cloacal
membrane, the future site of
the anus.
 FORMATION OF INTRAEMBRYONIC
MESODERM
 The epiblastic cells from the
primitive streak (groove)
proliferate to form
mesenchymal tissue

 The newly formed cells

invaginate and migrate
ventrally, laterally &
cranially between the
epiblast and hypoblast &
organize to form the
intraembryonic mesoderm
 FORMATION OF INTRAEMBRYONIC
MESODERM CONT’D
 Intraembryonic mesoderm
merges with the extra-embryonic
mesoderm at the periphery of the
embryonic disc

 By the end of 3rd week,

mesoderm lies between
embryonic ectoderm and
endoderm everywhere EXCEPT
in the region of prechordal plate
and cloacal membrane, as the
embryonic ectoderm &
endoderm are fused at these
regions
TRILAMINAR EMBRYONIC DISC
 FORMATION OF INTRAEMBRYONIC
MESODERM CONT’D
 Some mesenchymal cells
displace the hypoblasts
forming the embryonic
endoderm

 Cells remaining in the

epiblast form the embryonic
ectoderm
Thus the EPIBLAST gives rise to all three
germ layers, Ectoderm, Mesoderm, Endoderm
in the embryo

EACH OF THE THREE GERM LAYERS GIVES

RISE TO SPECIFIC TISSUES AND ORGANS
 FATE OF THE GERM LAYERS
 The ectoderm layer will give rise to neural tissue, as well
as the epidermis.

 The mesoderm develops into somites that differentiate

into skeletal and muscle tissues, the notochord, blood
vessels, dermis, and connective tissues.

 The endoderm gives rise to the epithelium of the

digestive and respiratory systems and the organs
associated with the digestive system, such as the liver and
pancreas.
 FATE OF PRIMITIVE STREAK
 Actively forms mesoderm until
the early part of 4th week

 Then it starts regressing and

becomes an insignificant structure
in the sacrocooccygeal regions

 Normally it degenerates and

disappears by the end of 4th week

 Remnants may persist and give

rise to a large tumor called
Sacrococcygeal Teratomas
 NOTOCHORD

 A rodof mesenchymal cells

located cranially, in the
midline, extending between
the primitive node and the
prechordal plate
FORMATION OF NOTOCHORD
 Mesenchymal cells migrate
cranially from the primitive
pit towards the prechordal
plate, and form a rod like
notochordal process

 The notochordal process

becomes canalized forming a
hollow tube, the notochordal
canal, communicating with
the primitive pit.
 FORMATION OF NOTOCHORD CONT’D
 Thefloor of the tube and the
underlying endoderm break
down, forming a
notochordal plate

 The notochordal plate

becomes continuous with
the endodermal layer.
 FORMATION OF NOTOCHORD CONT’D

 A temporary
communication is
established between
the amniotic cavity
and the yolk sac,
termed the
neurenteric canal.
NOTOCHORDAL PLATE FOLDS TO FORM THE NOTOCHORD.
 FUNCTIONS OF NOTOCHORD
 Defines primordial axis of the embryo
 Provides rigidity to the embryo
 Serves as a basis for the development of the axial
skeleton
 Indicates the future site of the vertebral bodies/column
 Regulates differentiation of surrounding structures
including the overlying ectoderm (neural plate) and
mesoderm (somites).
FATE OF
NOTOCHORD

 Degenerates and disappears

as the bodies of the
vertebrae develop, but it
persists as the nucleus
pulposus of each
intervertebral disc

 Remnants of notochordal
tissue give rise to tumors
called Chordomas
 ECTODERMAL DERIVATIVES
THE NEURULATION
 It is the process by which the neural tube is formed.
 The stages of neurulation include the formation of:

Neural plate
Neural groove

Neural folds & their fusion

Neural crest cells

Neural tube

 Begins during early part of the 4th week (22-23 days)

 Ends by the end of 4th week (27 days)
 Is induced by the notochord
 KEY POINTS
 The notochord stimulates neurulation in the ectoderm after its
development.

 The neuronal cells running along the back of the embryo form the
neural plate, which folds outward to become a groove.

 During primary neurulation, the folds of the groove fuse to form

the neural tube. The anterior portion of the tube forms the basal
plate, the posterior portion forms the alar plate, and the center
forms the neural canal.

 The ends of the neural tube close at the conclusion of the fourth
week of gestation.
 NEURULATION
 Neurulation is the folding inward and subsequent
internalization of surface ectodermal cells.

 It involves additional cell movement following gastrulation

to form neural tube, which gives rise to the central nervous
system- the brain most anteriorly and spinal cord posteriorly.

 The neural tube is a structure that runs along the anterior-

posterior axis on the dorsal side of the embryo.
 To a certain extent, neurulation actually begins while
gastrulation is still in progress.
 THE NEURULATION
 Under the
inducing effect
of the
developing

notochord, the
overlying
ectodermal cells
thickens to form
the neural plate
 The neural plate first
appears:
 Cranial to the
primitive node and
 Dorsal to the
developing
notochord & the
mesoderm adjacent
to it
 As the notochord forms &
elongates:
 The embryonic disc
elongates and becomes
club-shaped
 The neural plate broadens
and extends cranially as
far as the buccopharyngeal
membrane, and later on
grows beyond it
 Neural fold
 On 18th day: the neural
plate invaginates to form
neural groove & neural
folds.
 Some neuroectodermal cells along the crest of
the neural fold differentiate as the neural crest
cells.

Neural crest cells

Neural fold
 By the end of 3rd week, the
neural folds move to the
midline and fuse to form
the neural tube

 The fusion begins in the

future cervical region and
then extends both in
cranial and caudal
direction.
The neural tube separates from the surface
ectoderm, lies in the midline, dorsal to the
notochord
Neural tube is open at
both ends,
communicating freely
with the amniotic
cavity.
The cranial opening,
the rostral neuropore
closes at about 25th
day & the caudal
neuropore closes at
about the 27th day
The cranial ⅓ of the
neural tube represent
the future brain

The caudal ⅔
represents the future
spinal cord
 FOLDING OF
EMBRYO
o Folding means
conversion of the
flat trilaminar
embryonic disc into
a cylindrical
embryo.

o Time: Folding of the

embryo begins by the
end of the 3rd week
and it is completed by
4th week.
 Folding of the embryo is
due to rapid growth of
the embryo specially the
nervous system.

 The head folds first then

the tail . At the same
time, side to side folding
occurs.
WHAT IS NEURAL TUBE DEFECT ?
 Failure of normal fusion of the neural plate to form
neural tube during the first 28 days following conception
.

 Neural tube defects (NTDs) are one of the most

common birth defects, occurring in approximately one in
1000 live births in the United States.
 Prevalence
 Increased incidence in families of Celtic and Irish heritage .
 Increased incidence in minorities (genetic or environmental?)
 Increased incidence in families

 Neural tube defects (NTDs) are among the most

common birth defects that cause infant mortality (death)
and serious disability .
NEURAL TUBE DEVELOPMENT
 Normal embryological
development
 Neural plate
development -18th
day
 Cranial closure

24th day (upper

spine)
 Caudal closure

26th day (lower

spine)
ETIOLOGY OF NTDS

 Combination of environmental and genetic causes .

 Teratogens :

- Drugs
-Rdiation
 Infection and maternal illnesses.

 Nutritional deficiencies . - notably, folic acid deficiency

RISK FACTOR :
 All pregnancies are at risk for an NTD. However, women
with a history of a previous pregnancy with ( NTD).
 women with first degree relative with(NTD)

 women with type 1 diabetes mellitus

 women with seizure disorders on Na valproic acid.

 women or their partners who themselves have an NTD.

NTDS :
 Two types of NTDs:
1- Open NTDs ( most common) :
- occur when the brain and/or spinal cord are exposed at
birth through a defect in the skull or vertebrae.

 Spina bifida
 Anencephaly
 Encephalocele
2- closed NTDs (Rarer type ):
- occur when the spinal defect is covered by skin.

 lipomyelomeningocel
 lipomeningocele
 tethered spinal cord.
NEURAL TUBE DEFECTS
 What are the common Neural Tube Defects (NTDs) ?
 Spina Bifida - 60%

 Anencephaly - 30%

 Encephalocele - 10%
WHAT IS SPINA BIFIDA?
- A midline defect of the :
 bone,

 skin,

 spinal column, &/or

 spinal cord.
SPINA BIFIDA
 Spina Bifida is divided into two subclasses :

1 - Spina Bifida Occulta(closed ) :

- mildest form ( meninges do not herniate through the
opening in the spinal canal )

2 -Spina Bifida Cystic ( open) :

- meningocele and myelomeningocele .
SPINA BIFIDA
SPINA BIFIDA OCCULTA
 Failure of fusion of the vertebral arch .
 The meninges do not herniate through the bony defect. This lesion is
covered by skin.

Symptoms :
 Difficulties controlling bowel or bladder .
 weakness and numbness in the feet
 recurrent ulceration .
 In Diastematomylia neurological deficits increase with growth.

Signs :
 Overlying skin lesion :
 tuft hair - lipoma - birth mark or small dermal sinus

 Usually in the lumbar region .

 SPINA BIFIDA OCCULTA
 Diagnosis:
-indecently by X-ray.
- clinical.
SPINA BIFIDA MANIFESTA
 The 2 major types of defects seen here are
myelomeningoceles and meningoceles.
 lumobosacral regions are the most common sites for
these lesions .
 Cervical and thoracic regions are the least common
sites.
MYELOMENINGOCELE
MYELOMENINGOCELE
 The spinal cord and nerve roots herniate into a sac
comprising the meninges.

 This sac protrudes through the bone and

musculocutaneous defect.
MYELOMENINGOCELE
 Certain neurologic anomalies such as :
- hydrocephalus
- Chiari II malformation
MYELOMENINGOCELE
 myelomeningoceles have a higher incidence of
associated :
- orthopedic anomalies of their lower extremities ( why).
- Intestinal malformations.
- Cardiac malformations.
- esophageal malformations.
- renal and urogenital anomalies.
SYMPTOMS & SINGS :
 - Variable paralysis of the legs.
 - muscle imbalance .
 - Sensory loss .
 - bladder denervation ( neuropathic )
 - bowel denervation .
 - scoliosis .
 - Arnold chiari malformation .
 Diagnosis :

-Antenatal :
- Elevated Alfa fetoprotein .
-US (Polyhydramonis ) .

 At birth :
- Clinical finding .
ARNOLD CHIARI MALFORMATION
 Herniation of the cerebellar tonsils through the
foramen magnum .

 cerebellar hypoplasia .

 caudal displacement
of the hindbrain through .
the foramen magnum .

usually associated with

Hydrocephalus .
ARNOLD CHIARI MALFORMATION
 Hydrocephalus .
 Cranial Nerve Palsies .

 Visual Deficits .

 Pressure from the enlarged ventricles affecting adjacent

brain structures .
 Cognitive and perceptual problems.

 Motor dysfunction .
 MENINGOCELE

simply herniation of the meninges through the bony

defect (spina bifida).
MENINGOCELE

 Fluid-filled sac with meninges involved but neural tissue

unaffected .

 The spinal cord and nerve roots do not herniate into this
dorsal dural sac.

 The primary problems with this deformity are

cosmetic
MENINGOCELE
 Neonates with a meningocele usually have normal
findings upon physical examination and a covered
(closed) dural sac.

 Neonates with meningocele do not have associated

neurologic malformations such as hydrocephalus or
Chiari II.

 May complicted by CSF infection.

LIPOMENINGOCELE

 Lipomeningocele
(lipo = fat)

 lipoma or fatty tumor

located over the
lumbosacral spine.

 Associated with bowel &

bladder dysfunction
Lipomeningocele
PROGNOSIS OF SPINA BIFIDA
o static
o non-progressive defect
o with worsening from secondary problems.

- The prognosis for a normal life span is generally good for a

child with good health habits and a supportive
family/caregiver.
IMPAIRMENTS ASSOCIATED WITH
SPINA BIFIDA
 Abnormal eye movement
 Pressure sore and skin irritations.

 Latex allergy.

 Bladder and bowel control problems

 musculoskeletal deformities (scoliosis).
 joint and extremity deformities (joint contractures, club
foot, hip subluxations, diminished growth of non-
weight bearing limbs)
 Osteoporosis.

 tethered spinal cord after surgery .

 Treatment
 surgical

 Management
 Prenatal screening
 Triple Screen( alpha fetoprotein ,hcg ,esraiol )
 Ultrasound

 amniocentesis

 complex and life long

 Spine Xrays and/or spinal ultrasound
ANENCEPHALY
 Failure of development of most of the cranium and
brain.
 Infants are born without the main part of the
forebrain-the largest part of the cerebrum.
 The fetus usually blind, deaf and unconscious .
partially destroyed brain, deformed forehead, and large
ears and eyes with often relatively normal lower facial
structures.

 Both genetic and environmental insults appear to be

responsible for this outcome.

 The defect normally occurs after neural fold

development at day 16 of gestation but before closure
of the anterior neuropore at 24-26 days' gestation.
ANENCEPHALY
 Anencephaly is the most common major CNS
malformation in the Western world,
 no neonates survive. It is seen 37 times more in females
than in males.

 The recurrence rate in families can be as high as 35%.

ANENCEPHALY
 Symptoms
 Mom- Polyhydramnios
 Baby- absence of brain/skull

 Diagnosis
 Ultrasound

 Treatment
 None, incompatible with life
 Management
 Comfort Measures
 Support Parents
ENCEPHALOCELE
Extrusion of brain and
meninges through a
midline
Skull defect .

 - Often associated with

cerebral malformation
 DIAGNOSIS AND DETECTION
 Amniocentesis
 AFP - indication of abnormal leakage
 Blood test
 Maternal blood samples of AFP
 Ultrasonography
 For locating back lesion vs. cranial signs