13. Limb Devo

Question 1

areas of somatic mesoderm located on each side of the

embryo.

Answer 1

The Limb Fields

Question 2

Due to differential expression of_______ genes, the limb fields are localized at distinct axial levels, one for the upper limb and one for the lower limb

Answer 2

Hox

Question 3

Specific transcription factors are expressed within the upper limb_____ and the lower limb ______

Answer 3

(Tbx5)

Tbx4 & Pitx-1

Question 4

Limb bud outgrowth is initiated by signaling molecules

_______originating in the _______ mesoderm.

Answer 4

(FGF & Wnt)

intermediate

Question 5

Limb bud outgrowth is initiated by signaling molecules
(FGF & Wnt) originating in the intermediate mesoderm. These signals induce ______ expression in the appropriate areas of ________ resulting in limb bud formation.

Answer 5

FGF 10

lateral plate mesoderm

Question 6

forms skeletal elements, fibrous connective tissue and

dermis of the skin (probably vascular endothelium and smooth muscle)

Answer 6

Somatic mesoderm

Question 7

forms the epidermis of the skin

Answer 7

Surface Ectoderm

Question 8

migrates into the limb bud forming the skeletal muscle

Answer 8

Somitic (somite derived) mesoderm –

Question 9

Nerve fibers from ________ of spinal nerves migrate into the limb and become surrounded by neural crest-derived Schwann cells.

Answer 9

ventral primary rami

Question 10

Limb development occurs along three axes. Limbs elongate and limb segments are formed along the _______ axis.

Answer 10

proximal-distal

Question 11

Muscles and nerves are organized in

compartments along a _______ axis.

Answer 11

dorsal–ventral

Question 12

Digits are arranged along an _______ axis.

Answer 12

anterior-posterior

Question 13

After limb outgrowth is initiated, Fgf 10 produced by the somatic mesoderm of the
bud initiates the secretion of______ (also Fgf4 & 2) in the distal ectoderm. This results in a thickening of the distal ectoderm called the _________

Answer 13

Fgf 8

apical ectodermal ridge(AER).

Question 14

What defines the location of the ridge at the boundary between the dorsal and ventral surfaces of the limb? T

Answer 14

Differential gene expression in the dorsal and ventral surface ectoderm

Question 15

acts as a signaling center for the underlying

mesenchyme (originating from somatic mesoderm).

Answer 15

AER

Question 16

Signals from the AER (primarily Fgf 8) induce the adjacent mesenchyme to proliferate, which creates a
pool of mesenchyme cells that enable the limb ______

Answer 16

to elongate.

Question 17

_____ signals also inhibit mesenchyme differentiation and is secreated from the mesenchyme adjacent to the AER
to maintain AER function until all limb segments
are formed.

Answer 17

Fgf

Thus a positive Fgf feedback loop occurs between the mesenchyme (Fgf 10) and the AER (Fgf 8).

Question 18

The arrangement of the digits is achieved by signaling from the_________ on the posterior border of the limb just proximal to the AER.

Answer 18

Zone of Polarizing Activity (ZPA)

Question 19

The ZPA is an area of somatic mesenchyme on the posterior side of the limb bud that secretes

Answer 19

Sonic hedgehog (Shh)

Question 20

has been shown to mimic the action of Shh.

Answer 20

Retinoic acid

Question 21

Expression of Shh from the ZPA initiates the expression of a subset of the Hox genes in the posterior
mesoderm… how does this cause normal digit formation

Answer 21

Expression occurs in an overlapping nested fashion. This expression pattern of Hox genes as well as other signaling molecules

Question 22

The flat digital plate contains condensations of mesenchyme representing each digit called _____

Answer 22

digital rays

Question 23

The phalanges and joints will form from digital rays and initially they are joined together by a web of condensed mesenchyme. The AER in the web areas disappears and

Answer 23

triggers apoptosis within the web mesenchyme. This results in digit separation. The AER remains at the
distal tip of the digital ray until all parts of the digit have formed.

Question 24

How do we get vascular supply to developing muscles in the limbs?

Answer 24

Sprouts from several intersegmental arteries enter the limb bud and form a vascular network within the mesenchyme. Eventually one intersegmental
dominates as the primary axial artery. During development, the vascular network is remodeled into the mature vascular arrangement.

Question 25

The Preaxial channel in the upper limb becomes the ______, while that in the lower limb becomes the

Answer 25

cephalic vein

saphenous vein

Question 26

Nerve trunks from the _______ grow into thelimb bud and associate with the forming skeletal muscles, vessels and skin.,,,signals from mesenchyme at the base of the limb bud appear to direct nerve ingrowth.

Answer 26

forming brachial and lumbosacral plexuses

Question 27

Overall dorsal and ventral pattering is set up by

Answer 27

competing signals for the dorsal and ventral ectoderm.

Question 28

The upper limbs rotate______ and the lower limbs rotate _________

Answer 28

laterally

medially

Question 29

On average limb defects occur in

Answer 29

two per thousand live births

Question 30

When is limb development most sensitive to teratogenic development?

Answer 30

between the 4th to 9th weeks of development.

Question 31

is a potent teratogen that causes significant limb defects.

Answer 31

Thalidomide

Question 32

What is the difference between a defect and a deformation?

Answer 32

defect = morphological abnormality resulting from abnormal developmental mechanisms or processes, thus it is inherent to the process of development.
deformation=abnormal form, shape or position of a normally formed body part. Mechanical forces that impact the child as it develops cause deformations.

Question 33

These types of limb defects would be similar to
amputations along the proximal–distal axis. That is segments or parts of segments are missing distal to the “amputation”.

Answer 33

Transverse Type –

Question 34

The most severe form of Transverse type is

the absence of an entire limb, a condition called

Answer 34

Amelia

Question 35

Transverse type condition where only a segment or part of a segment is missing, e.g. a forearm and hand or a foot. These types of truncation are called

Answer 35

Meromelia.

Question 36

This subset includes defects were there are parts
missing within one or more segments of the limb. For example, the radius and
some digits, along the anterior-posterior axis may be missing or the fibula may be absent.

Answer 36

Longitudinal Type

Question 37

where the missing parts are in the median aspect of the distal limb segment, such as the middle digits, which creates a “lobster claw-like” deformity.

Answer 37

Oligodactyly

Question 38

(seal limb) where the most distal limb segment(s) is (are) attached to the limb girdle, e.g. the hand is
attached to the shoulder girdle or the foot to the pelvic girdle.

Answer 38

Phocomelia

Question 39

Syndactyly and Sirenomelia are both examples of

Answer 39

Failure of Differentiation or Separation of Limb Parts

Question 40

Digits may be completely or partially fused. Fusion may involve only the skin or may include fusion of the bones.

Answer 40

Syndactyly

Question 41

fusion of complete lower limbs or lower limbs represented by a conical stump, is the most extreme case of this type of anomaly.

Answer 41

Sirenomelia

Question 42

a condition where there is one or more extra digits. This may occur unilaterally or bilaterally.

Answer 42

Polydactyly

Question 43

where several digits as well as part of the hand or foot are duplicated.

Answer 43

Diplopodia

Question 44

bands of amnion can break free and wrap around portions of the fetus. Amniotic bands can wrap around a normally formed limb causing a severe constriction or amputation

Answer 44

Congenital Constriction Band Syndrome

Question 45

Clubfoot (also called talipes) is any defect involving the ____ bone.

Answer 45

talas

Question 46

the foot is plantar-flexed (like a horse’s

foot), inverted and adducted (varus). This type is twice as common in boys as in girls.

Answer 46

talipes equinovarus,

Question 47

Cause of Clubfoot

Answer 47

Some believe that most instances of
clubfoot represent a defect the repair of which may involve some surgical as well
as casting procedures. A clubfoot may also be acquired when the foot becomes
located in an abnormal position within the uterus. Clubfoot is often isolated but it
is part of some syndromes. Multifactorial inheritance may also play a role.

Question 48

Developmental Dysplasias: The major problem is that the hip is for some reason

Answer 48

more susceptible to dislocation after birth.

Question 49

Reasoning for Developmenta Hip Dysplasia

Answer 49

This is compounded by the fact that normally at birth the hip joint is somewhat immature and malleable to aid in
the birth process. The thinking regarding this defect is that the hip joint is more insufficiently formed than usual. Congenital hip dysplasia is often associated
with breech births and with a syndrome of generalized joint laxity.

Question 50

What conditions during pregnancy and birth may also contribute to developmental hip dysplasias?

Answer 50

Hormones that make the maternal connective tissue soft at childbirth

Question 51

Pattern of susceptibility for developmental hip dysplasias?

Answer 51

more common in females and may be unilateral or bilateral. The defect tends to run in families

Question 52

characterized by an undescended scapula.
Normally the scapula is located between T2-T7. In this
deformity it is located at C4-T2. The muscles associated with the scapula are hypoplastic or atrophic which limits shoulder movement and is disfiguring.

Answer 52

The Sprengel Deformity

Question 53

Sprengle deformity shows a 3:1 predominance in_____. Usually there are associated anomalies of the_____.

Answer 53

males

spine

Question 54

People with this deformity have a variety of anomalies that include hypoplasia or aplasia of the clavicles, large head, small face, long neck, and a short narrow chest. They also have short fingers and dental problems.

Answer 54

Cleidocranial Dysplasia

Question 55

Cause of Cleidocranial Dysplasia

Answer 55

defect in Runx-2.