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77 Cards in this Set

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During which week does the upper limb appear?
mid 4th week
During which week does the lower limb appear?
end 4th week
From which part of the body wall does the limb bud project?
Ventrolateral body wall
From which region does the upper limb bud from?

Lower limb?
Lower cervical region (C5-T1)

Lumbosacral region (L1-S3)
Describe the organization of the limb bud. (Core composition and what covers it)
Mesenchymal core covered by surface ectoderm
What types of mesoderm form the mesenchymal core?
1. Somatic mesoderm (forms connective tissue and skeleton)
2. Somitic mesoderm (myotome portion of somites invade core and form skeletal muscle)
Which mesoderm forms the connective tissue and skeleton of the limb bud?
Somatic mesoderm (from lateral plate mesoderm)
Which mesoderm forms skeletal muscle?
Somitic mesoderm (myotome portion)

(sclerotome portion forms axial skeleton)
The limb bud is elongated in the _______ axis and narrow in the ________ axis.
Elongated = craniocaudal axis
Narrow = dorsoventral axis
Growth of the limb bud begins along which axis?
Proximal-distal axis
(shoulder-->hand)
List the 3 axes that limb buds grow in.
1. Proximodistal
2. Craniocaudal
3. Dorsoventral
What regulates the proximal-distal limb growth?
Apical ectodermal ridge (AER)
What is the apical ectodermal ridge (AER) composed of?

What induces its formation?
Thickened ectoderm at apex of limb bud

Induced to form by underlying mesenchyme.
What is necessary for the development and growth of the limb bud?
Apical ectodermal ridge (AER)
Proximal-distal growth is regulated by _____ and _____ signaling events in AER and underlying mesenchyme.
Fgf and Wnt
Absence of a limb is known as...?

Partial absence of a limb is known as...?
Amelia

Meromelia
If AER is injured during limb development there will be ______ (proximal/distal) deletions
Distal
Which genes are important in proximal-distal limb development that control temporal and spatial expression?
Hox genes
Which growth axis is influenced by the Zone of polarizing activity (ZPA)?
Craniocaudal axis
The zone of polarizing activity establishes gradients of which 2 morphogens?
1. Sonic hedgehog (Shh)
2. Retinoic acid
A high concentration of retinoic acid will encourage ______ (cranial/caudal) directionality.
Caudal
Which growth axis is regulated by signals from the mesenchyme and then from the ectoderm?
Dorsal-ventral axis
Which gene is expressed in the dorsal mesenchyme and regulates activity of Wnt7a which is expressed in the dorsal ectoderm?
Lmx1b homeobox gene

(responsible for dorsal-ventral axis)
What will be the result of a mutation of Lmx1b in humans?
Nail-patella syndrome
(very small fingernails and absence of patella.
Lmx1b (along with Wnt7a) is involved in dorsoventral axis development)
Between which weeks of development does the limb bud differentiate?
4th - 8th
During which time period are limbs the MOST sensitive to teratogens?
4th - 5th weeks
The limb is fully developed by which week?
8th week
Which structures are formed in the hand and foot plates when the mesenchyme condenses and patterned outlines of the digits are visible?
Digital rays

(AER is maintained at tips)
Which areas of the hand and foot plates lose AER (undergo programmed cell death)?
Interdigital zone
Which factors are expressed in the interdigital mesodermal cells that are involved in the signals leading to cell death?
1. BMPs
2. Retinoic acid receptor B
3. Msx-1
If cell death does not occur in the interdigital zone, what growth abnormality occurs?
Syndactyly
What growth abnormality results from addition digital rays?
Polydactyly
Explain the difference between the rotation of the upper limbs and lower limbs during development.
Upper limb rotates laterally
Lower limb rotates medially

(Thumbs point laterally, big toes point medially)
Describe the difference in placement of flexors/extensors in the upper limb verses those in the lower limb.
Flexors/extensors have opposite placements in the upper and lower limbs.

Upper limb: flexors are ventral, extensors are dorsal

Lower limb: flexors are dorsal, extensors are ventral
During endochondral ossification, where do primary centers of ossification form?
Diaphysis

(blood vessels bring osteoblasts here)
During endochondral ossification, where do secondary centers of ossification form?

When do they form?
Epiphysis of long bones

Do not appear until AFTER birth
After birth, which areas of long bones continues to grow?
Epiphyseal plates
(located between epiphysis and diaphysis on both ends of bone)
Describe the 4 steps of endochondral ossification.
1. Aggregation of mesenchyme --mesoderm (early 5th week)
2. Cartilage model formed (5th - 7th week)
3. Blood vessels bring osteoblasts--primary centers of ossification begin in diaphysis (7th week)
4. Secondary centers of ossification form in epiphysis AFTER birth
Synovial joint development forms from mesenchyme in which area?
Interzonal area
What does interzonal mesenchyme form?
Articular cartilage on joint surfaces of neighboring bones
Describe the structures formed from the center layer of interzonal mesenchyme.
1. Internal structures of joint--menisci, enclosed joint ligaments
2. Synovial cavity
Describe the structures formed from the outer layer of interzonal mesenchyme
1. Joint capsule
2. Synovial membrane
What types of muscles are formed in ventral muscle mass?
Flexors
Adductors
Pronators
What types of muscles are formed in dorsal muscle mass?
Extensors
Abductors
Supinators
The ______ primary rami from segmental spinal nerves provide motor innervation to the limbs.
Ventral primary rami
(penetrate ventral and dorsal muscle masses)
Name the 2 plexi that supply the upper extremity and the lower extremity.
Upper extremity --> brachial plexus
Lower extremity --> lumbosacral plexus

(both formed by ventral primary rami of segmental spinal nerves)
What is the term for the area of skin innervated by a single spinal nerve?
Dermatome
Describe the initial organization of dermatomes?
(which axes does the formation follow?)
Cranial to caudal and proximal to distal

(later, rotation of the limbs cause dermatomes to spiral down limb)
Term for anomaly in which distal structures are fully formed but proximal structures are absent.
Phocomelia
Syndactyly results from a mutation in which gene?
HoxD13
List 4 causes of limb abnormalities.
1. Genetic factors (polydactyly, syndactyly..)
2. Environmental factors (teratogens--> meromelia, phocomelia..)
3. Mechanical (amniotic band syndrome)
4. Multifactorial (club foot)
Name 2 teratogens that result in severe limb anomolies.
1. Thalidomide
2. Retinoic acid (accutane)
Which congenital anomolies typically result from thalidomide?
1. Phocomelia
2. Meromelia
Clubfoot is any deformity of the foot involving the ______.
Talus
What mechanical and genetic factors can result club foot?
1. Abnormal intrauterine position
2. Genetic predisposition
Which week of embryonic development is characterized by the appearance of the primitive streak, notochord, and 3 germ layers?
3rd week
During which developmental process are the three germ layers formed?
Gastrulation
(bilaminar disc is converted into a trilaminar embryonic disc)

*occurs during 3rd week of development
Which germ layer gives rise to the:
1. epidermis
2. Central/peripheral nervous system
3. Eye
4. Inner ear
6. Neural crest cells
7. Many connective tissues of the head
Ectoderm
Which germ layer is the source of
1. Epithelial linings of the respiratory and digestive tracts
2. Glands opening into the GI tract
3. Glandular cells of associated organs (liver, pancreas)
Endoderm
Which germ layer gives rise to all skeletal muscles?
Mesoderm
Which germ layer gives rise to blood cells and the lining of blood vessels, all visceral smooth muscular coats, the serosal linings of all body cavities, the ducts and organs of the reproductive and excretory systems, and most of the cardiovascular system?
Mesoderm
Which germ layer gives rise to all connective tissues, including cartilage, bones, tendons, ligaments, and skeletal muscle?
Embryonic mesoderm
What is the first sign of gastrulation?
Appearance of the primitive streak
How is the zone of polarizing activity activated?
Fibroblast growth factors from the AER activate it.
Blocking the signaling events of bone morphogenic proteins (BMPs) may result it what type of anomoly?
Syndactyly
(webbing of the fingers or toes)

*BMPs play a role in apoptosis in the interdigital zones
Digital rays begin to appear in the foot during which week of development?
Week 7
Separation of the digits occurs by which week?
Week 8
By which week of development are ossification centers present in all long bones?
Week 12
The primary axial artery becomes the _______ artery in the arm and the _______ artery in the forearm.
Primary axial artery--->
Brachial A in ARM
Common interosseous A in FOREARM
The primary axial artery becomes the _______ in the thigh and the ________and ________ arteries in the leg.
Primary axial artery --->
Deep artery of the thigh (Profunda femoris A)
Anterior and posterior tibial arteris in leg
During which week of development do finger and toenails begin to appear?
Week 10
Which axons arising from the spinal cord enter the limb bud first--motor or sensory?
Motor enter first (week 5) and sensory axons follow, using the positioning of motor axons for guidance.
What the is first blood vessel to supply the developing limb?
Primary axial artery
During development, what arteries arise from the aorta and supply the limb buds?
Intersegmental arteries
Suppression of limb bud development during the early part of the 4th week will result in what type of limb anomaly?

A disturbance during the 5th week will result in...?
4th week --> amelia
5th week --> meromelia
Anomaly that results from a reduction in the length of the phalanges, causing shortness of the digits.
Brachydactyly
What is the most common anomaly of the hand or foot?
Syndactyly