Embryology

Question 1

Early Stages - when does growth of the limbs begin? and what is it due to?

Answer 1

• Begins near the end of 4th week
• Activation of mesenchymal cells in the somatic lateral mesoderm - embryonic connective tissue, undifferentiated
• Homeobox genes regulate patterning - regulate development of the limbs as needs to be precise

Question 2

what do the upper and lower limbs grow from and when does this occur?

Answer 2

Around cervical and lumbar region you can see upper and lower limb bud

• Day 24 – Upper limb bud appear
• 1 to 2 days later – Lower limb bud appear

Question 3

Proximo-distal patterning - HOX genes - what is their function?

Answer 3

Regionally expressed in limbs and determine which skeletal element formed HOX gene expression results from a combination of the expression of SHH, FGF’s and WNT-7a

HOXd 9-13 genes expression in upper limb

Remove HOXa 11 and HOXd 11 and the radius and ulna do not form

Question 4

Limb buds:

• Limb buds elongate by the proliferation of ___________
• Upper limb buds develop opposite the caudal _______ segments
• Lower limb buds form opposite the _____ and _____ segments

Answer 4

mesenchyme

cervical

lumbar

sacral

Question 5

what is found at the apex of each limb bud?

Answer 5

•At the apex of each bud the ectoderm thickens to form an apical ectodermal ridge (AER)

Question 6

what is the Apical Ectodermal Ridge (AER)?

Answer 6

• AER restricted to end of limb bud
• Multilayered epithelial structure
• Exerts an inductive influence on the limb mesenchyme
• The mesenchyme adjacent to the AER consits of undifferentiated, rapidly proliferating cells
• whereas mesenchymal cells proximal to it differentiate into blood vessels and cartilage bone models

Question 7

Describe the development of hand & foot plates

Answer 7

• The distal ends of the limb buds flatten into paddle-like hand plates and flipper-like foot plates
• By the end of 6th week, mesenchymal tissue in hand plates has condensed to form digital rays
• During the 7th week digital rays are formed in the foot plates

Question 8

what happens to the skin inbetween the fingers and toes?

Answer 8

Programmed cell death (apoptosis) is responsible for the tissue breakdown in the interdigital regions – mediated by bone morphogenetic proteins

Question 9

Describe what happens in the final stages of limb development

Answer 9

• Cartilaginous precursors of the limb bones develop by chondrification within the mesoderm in the 6th week
• Primary centres of ossification appear in weeks 8 to 12 in response to growth factors
• Endochondrial ossification for all limb bones except the clavicle (membranous)

Membranous – mesenchymal tissue converts directly to bone

Endochondral – mesenchymal tissue turns into cartilage and is infiltrated by developing blood vessels then turns into bone

Question 10

what limb rotation occurs?

Answer 10

• Upper limbs and lower limbs rotate
• Upper limbs rotate 90^o laterally so that extensors are on the lateral and posterior surfaces (and the thumb is lateral)
• Lower limbs rotate 90^o medially so that the extensors are on the anterior surface (and the big toe is medial)

Question 11

how does the development of the dermatomal patterns of the limbs occur?

Answer 11

During the 5th week, peripheral nerves grow from the developing limb plexus (brachial and lumbosacral) into the mesenchyme of the limbs

Originally the nerves in a vertical arrangements

Question 12

Birth Defects of Limbs

Often associated with other defects – hereditary or teratogen

what does amelia and meromelia mean?

Answer 12

Total absence (amelia), partial absence (meromelia)

Question 13

Birth Defects of Limbs

Often associated with other defects – hereditary or teratogen

what does phocomelia mean?

Answer 13

Some long bone absence (phocomelia)

Question 14

Birth Defects of Limbs

Often associated with other defects – hereditary or teratogen

what does micromelia mean?

Answer 14

All parts present but small (micromelia)

Question 15

what is this due to?

Answer 15

Lobster claw foot can be inherited as an autosomal dominant trait

Question 16

Critical period of limb development is when?

Answer 16

24-36 days after fertilization

Question 17

what is Polydactyly?

Answer 17

• Presence of more than 5 digits on the hands or feet
• Extra digit is incompletely formed and lacks muscular development
• May be inherited or teratogen induced

Question 18

what is Syndactyly?

Answer 18

• Common birth defect of the hand or foot
• Cutaneous Syndactyly (simple webbing between the digits) is a common limb defect
• More frequent in the foot than in the hand
• Osseous Syndactyly (fusion of bones) occurs when notches between the digital rays fail to develop

2 types – cutaneous and osseous. Cutaneous is simple webbing but osseous is to do with joining/fussing of bones

Question 19

what is Thalidomide and its effects?

Answer 19

• 1957-1962 used as a sleeping tablet and anti-nauseant
• Absence or deformity of long bones (intestinal atresia and cardiac anomalies)
• ‘Sensitive’ period 4-8wks
• Acts by disrupting cell adhesion and angiogenesis
• Now used to help cancer, leprosy and AIDS patients

Question 20

what is Congenital Clubfoot?

Answer 20

• Also known as TALIPES EQUINOVARUS (Club foot)
• Relatively common birth defect
• Sole of the foot is turned medially and the foot is inverted
• Cause: 1) Multifactorial (genetic and environmental factors)
• 2) ? Abnormal positioning or restricted movement of the fetus’s lower limb in the utero – Evidence is inconclusive

Question 21

How does Developmental Dysplasia of the Hip occur?

Answer 21

Abnormal development of acetabulum:

• 15% of infants with congenital dislocation of the hip
• Common after breech(buttocks) deliveries -? Breech posture during late part of pregnency (abnormal development of acetabulum and head of femur

Generalized joint laxity:

• Multifactorial
• Associated with congenital dislocation of hip

Question 22

Case study 1:

A neonate presented with clubfeet. The duty doctor explained to a group of medical students that this is a common birth defect.

• What is the most common type of club foot?
• How common is it?
• Describe the feet of infants born with this birth defect

Question 23

Case study 2:

A baby was born with syndactyly (webbing between her fingers). The plastic surgeon examined the baby and assured the parents that this minor defect can be easily corrected surgically

• Is syndactly common?
• Does it occur more often in the hands than in the feet?
• What is the developmental basis of syndactyly?