Embryology

Question 1

Neurulation

Answer 1

A. Begins with the formation of the neural plate which is induced to form by the notochord.
B. Next, the lateral edges of the neural plate elevate to form the neural groove.
C. Neural groove fuses, forming neural tube.
1. Originally open cranially and caudally (neuropores)
2. Cranial neuropore closes on day 25; caudal on day 27
D. The neural tube will form CNS (the brain and spinal cord)

Question 2

Neural Crest Cells

Answer 2

1. Arise from neuroectoderm as the neural tube is closing (not part of the neural tube).
2. Migrate into underlying mesoderm.
3. Fate of cranial neural crest:
   a. Bones, cartilage, fascia, ligaments and tendons of face, neck.
   b. Sensory ganglia, autonomic ganglia of cranial nerves
4. Fate of spinal neural crest:
   A. Dorsal root ganglia, autonomic ganglia
   b. Heart (fibrous skeleton)
5. Shared fate of cranial and spinal neural crest:
   a. Meninges, schwann cells
   b. Melanocytes

Question 3

neural crest derivatives

Answer 3

connective tissue and bones of face and skull
cranial nerve ganglia
c cells of the thyroid gland
conotruncal septum in the heart
odontoblasts
dermis in face and neck
spinal (dorsal root) ganglia
sympathetic chain and preaortic ganglia
parasympathetic ganglia of the gastrointestinal tract
adrenal medulla
schwann cells
glial cells
meninges (forebrain)
melanocytes
smoothmusscle cells to blood vessels of the fce and forebrain

Question 4

Spinal Cord

Answer 4

A. Neural tube caudal to 4th pair of somites forms spinal cord.

B. Three different regions form in neural tube form as a result of neuron migration from the neuroepithelium – ventricular, mantle, and marginal zones.

Question 5

Ventricular zone

Answer 5

1. Embryo – composed of the thick, pseudostratified epithelium called the neuroepithelium; will give rise to all neurons and most glia of spinal cord.
2. Adult – composed of simple layer of ependymal cells.

Question 6

Mantle zone

Answer 6

1. Zone superficial to neuroepithelium
2. Embryo – location of cell bodies of neuroblasts (primitive neurons)
3. Adult – inner gray matter
4. Alar and basal plates will form within the mantle layer.
   a. Alar plate will form sensory, dorsal horn of gray matter.
   b. Basal plate will form motor, ventral horn of gray matter

Question 7

Marginal zone

Answer 7

1. Outermost layer
2. Embryo – location of fiber processes of neurons (axons, dendrites)
3. Adult – external white matter

Question 8

Spinal nerves

Answer 8

1. Ventral nerve root formed from neurons derived from the basal plate
2. Dorsal nerve root formed from neurons derived from neural crest (dorsal root ganglion cells)
3. Dorsal and ventral rami form when the somite splits into dorsal and ventral portions (see below)
4. Dorsal rami will innervate muscles, skin, joints, of back and ventral rami will innervate the limbs, ventral body wall.

Question 9

Positional changes of spinal cord

Answer 9

1. 3rd month – spinal cord extends entire length of vertebral column.
2. At birth, spinal cord ends at about LV3.
3. In the adult, spinal cord ends at about LV1-LV2.

Question 10

Patterns of somatic innervation

Answer 10

A. Neuronal Pathfinding – active movement of axon toward an end organ or target. The nerves follow signals released from the paraxial mesoderm (the somite).

B. The dorsal and ventral rami form when the somite splits into dorsal and ventral portions.

1. Epimere (dorsal) – dorsal ramus
2. Hypomere (ventral) – ventral ramus

C. Motor and sensory innervation also established as spinal nerve innervates the somite.

1. Myotome – skeletal muscle innervated by one spinal nerve.
2. Dermatome - the area of skin innervated by one spinal nerve.

Question 11

Spina Bifida

Answer 11

(most often occurring in lumbosacral region)
1. Cause: neural tube does not completely fuse. This also results in a fusion defect in the overlying bony structure (vertebral arch). The spinous processes are underformed or not formed at all and the vertebral canal remains open posteriorly.

2. Types
   a. Spina bifida occulta (affects 15-20% of population). Typically does not involve menginges or nervous tissue; only involves bony defect. Often marked by a small patch of hair overlying the defect.

b. Spina bifida cystica involves the formation of a cyst overlying the vertebral defect.
1. Meningocele – cyst contains meninges and CSF
2. Meningomyelocele – cyst contains meninges, CSF, and spinal cord or spinal nerves)

c. Spina bifida with myeloschisis is the most severe form of spina bifida. Results when the neural plate fails to elevate and fold. The spinal cord remains open and is represented as a flattened mass of nervous tissue.

Question 12

Somites

Answer 12

A. Sclerotome: axial skeleton (vertebral column, ribs, portion of skull)
B. Dermotome: dermis
C. Myotome: skeletal muscle

Question 13

Vertebral Column

Answer 13

A. During week 4, cells of the sclerotome shift to surround the spinal cord and notochord.
B. Resegmentation
1. Original sclerotome separates into cranial and caudal halves.
2. Caudal portion of each sclerotome proliferates and fuses to the cranial half of the next sclerotome; original sclerotome splits.
3. Each vertebra is formed from caudal half of one somite and cranial half of neighbor.
a. Example: atlas (CV1) is formed from caudal half of first cervical sclerotome and cranial half of second cervical sclerotome.
2. Intervertebral discs
a. Annulus fibrosis from mesenchymal cells which remain between the cranial and caudal portions of the original sclerotome.
b. Nucleus pulposus from notochord.
3. The rearrangement of the sclerotomes results in:
a. The myotomes spanning the intervertebal discs.
b. Spinal nerves exit between contiguous vertebrae.
c. Intersegmental arteries pass midway over vertebral bodies.

Question 14

Congenital malformations of vertebrae

Answer 14

spina bifida, congenital scoliosis, klippel-feil,

Question 15

Congenital scoliosis

Answer 15

a. Cause: one half of vertebrae does not ossify.

b. Leads to abnormal lateral curvature of vertebral column.

Question 16

Klippel-Feil Syndrome

Answer 16

a. Cause: Fused cervical vertebrae due to a lack of resegmentation.
b. Results in short neck, restricted neck movements
c. Cause seems to be genetic; not fully understood.

Question 17

Ribs

Answer 17

A. Origin: paraxial mesoderm, sclerotome
B. Develop from costal processes of the 12 thoracic vertebrae
C. CLINICAL CORRELATION – accessory cervical and lumbar ribs can form if the costal processes on these vertebrae are signaled to develop.

Question 18

Sternum

Answer 18

A. Origin: lateral plate mesoderm, somatic layer
B. Ventral somatic mesoderm forms a pair of vertical bands called sternal bars.
C. CLINICAL CORRELATION: Pectus excavatum (anterior thoracic wall sunken-in) and carinatum (anterior thoracic wall protrudes) are congenital anomalies resulting from an overgrowth of the ribs. Most cases are purely cosmetic, but severe cases can cause respiratory and cardiac problems.

Question 19

Brief overview of muscle types and formation (trunk musculature)

Answer 19

A. Skeletal muscle arises from paraxial mesoderm (somites).
B. The majority of smooth muscle arises from splanchnic lateral plate mesoderm.
C. Cardiac muscle arises from a specialized region of splanchnic lateral plate mesoderm.

Question 20

Formation of skeletal muscle

Answer 20

A. Derived from myotomes of somites.

B. Each myotome splits into dorsal and ventral portions.

1. Dorsal part = epimere
   a. Innervated by dorsal rami
   b. Gives rise to intrinsic back muscles.
2. Ventral part = hypomere
   a. Innervated by vental rami
   b. Gives rise to anterior and lateral neck musculature, trunk muscles, limb musculature.

Question 21

Skeletal Muscle Myogenesis

Answer 21

1. Mesoderm cells differentiate into myoblasts (primordial muscle cells)
2. Myoblasts elongate and fuse together to form myotubes.
3. Soon after the formation of myotubes, contractile filaments appear in the cytoplasm of the myotube, now called a muscle fiber.

Question 22

Congenital Malformations of Trunk Musculature: Poland syndrome

Answer 22

1. Absent or underdeveloped pectoralis muscles.
2. Usually unilateral; usually right side affected.
3. Most cases also include syndactyly of the fingers.
4. Cause is unknown, but believed to involve loss of blood supply to the chest wall during development.

Question 23

Limb component – embryological structure

Answer 23

A. Skeletal and CT components derived from lateral plate mesoderm.
B. Muscle derived from the myotome of somites.
C. Epidermis from surface ectoderm.

Question 24

Limbs Buds

Answer 24

A. Limb buds form on ventrolateral body wall

1. Upper– (day 26 or 27) – form opposite lower cervical and upper thoracic segments.
2. Lower– (days 27 or 28) – form opposite lumbar and upper sacral segments.

B. At the apex of the limb bud is an ectodermal thickening called the apical ectodermal ridge (AER).

1. Mesenchymal cells deep to the AER remain in an undifferentiated, rapidly dividing state (AER induces continued proliferation of distal limb bud mesenchyme).
2. More proximally situated mesenchymal cells differentiate into cartilage cells (chondroblasts), forming early bone models, blood vessels, and other CT types.

C. Hand- and footplates (week 5)

1. Distal ends of limb buds flatten to paddle-like hand and footplates.
2. Separated from limb bud by circular constriction (future wrist or ankle joint).

D. Digital Rays

1. 4 zones of apoptosis separate AER of hand- and footplates into 5 digital rays.
   a. 6th week for upper limb
   b. 7th week for lower limb
2. Will form future toes/fingers

Question 25

Amelia

Answer 25

absence of limb due to suppression of limb bud development during week 4 of development. Most likely cause is faulty signaling from AER (or tissue is unresponsive to AER signaling).

Question 26

Meromelia

Answer 26

1. Absence of part of a limb. 2. Cause: arrest of limb bud development during weeks 5-7 of development. 3. Phocomelia is a type of meromelia involving the absence of the long bones.

Question 27

Digit deformities | Brachydactyly, syndactyly, polydactyly, ectrodacctyly

Answer 27

1. Brachydactyly: shortness of digits caused by insufficient production of mesoderm by digital rays. 2. Syndactyly: fusion of two or more digits a. Most common anomaly of hand/foot. b. Results from insufficient apoptosis of mesenchyme between digital rays. 3. Polydactyly: extra fingers or toes (1:500 birth) 4. Ectrodactyly: absence of digit

Question 28

Cleft hand or foot (lobster claw deformity)

Answer 28

1. Absence of third metacarpal (or metatarsal) and 3rd digit. 2. Fusion of first and second digits, fusion of fourth and fifth digits.

Question 29

Limb Axes

Answer 29

1. Proximal-distal axis (shoulder versus hand) is determined by the AER. 2. Anterior-posterior axis defines difference between thumb (anterior) and little finger (posterior); determined by the zone of polarizing activity 3. Dorsal-ventral axis defines difference between back of the hand (dorsal) to the palm (ventral).

Question 30

Ossification

Answer 30

A. During week 5, cartilage formation begins. B. Primary ossification centers form starting in the seventh week a. Present in all long bones by the 12th week b. Some bones begin ossification after birth (carpals, tarsals, patella) C. Secondary ossification centers form mostly after birth.

Question 31

Joints

Answer 31

Joints are formed in areas where mesenchyme is less dense (interzones). B. Joint cavity is formed by cell death; surrounding cells differentiate into joint capsule.

Question 32

Limb musculature

Answer 32

A. 5th week – myotome cells of the somite migrate into the limb bud. B. Myoblasts split into a ventral (flexor) and a dorsal (extensor) compartment. C. Myogenesis 1. Mesoderm cells differentiate into myoblasts (primordial muscle cells) 2. Myoblasts elongate and fuse to form myotubes. 3. Contractile filaments appear in cytoplasm of the myotube, now called a muscle fiber.

Question 33

Limb rotation

Answer 33

A. Dr. Funk’s description of limb rotation: When the upper and lower limbs originally form, they are directed laterally and caudally with the thumb and great toe facing laterally. The flexor surface faces ventrally and the extensor surface dorsally. In week 6, the limbs rotate (about 90 degrees) and bend to a more ventral position with the flexor surfaces now directed medially and the extensor surfaces laterally. In week 7, both limbs rotate, but in opposite directions. The upper limb rotates laterally 90o. As a result the flexor and extensor compartments are located ventrally and dorsally respectively (essentially back to its original position). The lower limb rotates another 90o medially (180 total). Thus, the lower limb flexor compartments are now dorsal and extensor compartments are not ventral (essentially the opposite position as where the limb started). B. Langman’s description of upper limb rotation 1. Rotates laterally (about 90°) 2. Elbow points dorsally, thumb is lateral 3. Flexor musculature lies on ventral (anterior) surface 4. Extensor musculature lies on dorsal (posterior) surface C. Langman’s description of lower limb rotation 1. Rotates medially (about 90°) 2. Knee points ventrally, great toe is medial 3. Flexor musculature lies on dorsal (posterior) surface 4. Extensor musculature lie on ventral (anterior) surface

Question 34

Innervation of limbs

Answer 34

A. Sensory nerve fibers are “pulled” into limb as it elongates from trunk. 1. Spinal nerves migrate along with dermatomes as they are pulled into developing limb; sensory innervation is distributed radially 2. Dermatomes “spiral” around limbs (especially lower) due to limb rotation. B. Motor nerve fibers grow into the limb along with myotomal mesoderm 1. Divide into anterior (flexor muscles) and posterior (extensor muscles) divisions. 2. Upper spinal nerves supply more proximal muscle masses and lower spinal nerves supply more distal muscles masses; motor innervation is distributed longitudinal

Question 35

Congenital clubfoot

Answer 35

1. Abnormal position of foot: foot is hyper-inverted and hyper-plantar flexed. 2. Common cause is oligohydramnios (too little amnionic fluid) which leads to abnormal positioning/restricted movement of the foot in utero.

Question 36

Amniotic bands

Answer 36

1. Caused by fibrous bands of amnion membrane in amniotic fluid. These bands can encircle and entrap portions of the fetus, cutting off circulation as fetus develops. 2. May cause amputations of limbs or digits.

Question 37

Congenital hip dislocation

Answer 37

1. Underdevelopment of acetabulum and head of femur, laxity of joint capsule 2. Dislocation occurs before birth 3. Common with breech deliveries