Limb Development

► Limb abnormalities and dysfunctions are among the most commonly encountered congenital
problems in domestic animals. This is due to the following reasons:

1. The appendicular tissues are particularly sensitive to both genetic (intrinsic) and
environmental (extrinsic) disturbances during the stages at which morphogenetic tissue
interaction are occurring

2. Relative autonomy of the developing limb. This contrasts with defects involving the notocord,
liver, kidney and other visceral organs which are more likely to be lethal in uteri or in early
postnatal stages, and are less frequently encountered in clinical practice

► All appendicular connective tissue arise from the lateral plate mesoderm, while voluntary
(skeletal) muscles are derived from the somites (paraxial mesoderm) specifically the myotome.
► The critical period of limb development is coincidental with the time at which the nerves, blood
vessels, muscles, skeletal and connective tissues in the limb are shaped (morphogenesis) and
internally organized (patterning)
► The stages of morphogenesis and patterning are followed by a period of rapid growth during
which the muscles and skeletal tissues mature, tendons and ligaments are formed and joints
develop. For the joints to develop, it is necessary that the limb be functionally innervated and
moving, otherwise, ankylosis (fixation of the joint) occurs. This stage lasts until the animal has
reached its adult size.

STAGES OF LIMB DEVELOPMENT

1. Aggregation of lateral plate somatic mesoderm beneath the surface ectoderm at four sites to
mark the

2. Formation of the limb buds

3. Enlargement of the limb buds

4. Thickening of the surface ectoderm in the distal margin of the limb bud. This thickening is called
the apical ectodermal ridge. Normal limb development is dependent on the interaction between
the limb bud mesoderm and the apical ectodermal ridge

5. Distal elongation of the limb bud. As this occurs, the mesenchyme within the bud forms two
morphologically distinct populations

a. Proximal population- forms chondrogenic condensations that soon develops into the scapula
or pelvis, then later, the humerus or femur.

b. Distal population- gives rise to the middle, distal (tarsal and carpal) and phalangeal structures

► The elongating limb becomes flattened in the dorsoventral plane of the embryo, and the distal
part acquires a paddle shape. As distal outgrowth continues, the limb bends ventrally so that the
original ventral surface of the limb becomes the medial surface.
 ► Subsequently, the limb rotate, which brings the cranial margin of the distal part of the limb
medially. The first digit then, is derived from the tissues originally located in the cranial part of the
limb bud.
► Areas of cell death called necrotic zones appear within the mesenchyme located immediately
beneath the cranial and caudal ectoderm.
► The limb bud is invaded by angiogenic cords, the primordia of endothelial lining of blood vessels
► Nerves enter the limb shortly thereafter
► After the myogenic primordia enter the limb bud from the ventral part of the adjacent somites,
they form two distinct condensations called dorsal and ventral muscle masses. These
condensations subsequently segregate into the primordia of individual muscles.

MECHANISMS OF LIMB DEVELOPMENT

1. Limb-forming mesenchyme is unique in its ability both to initiate the formation of an apical
ectodermal ridge (AER) and to provide for maintenance of the AER. This mesenchyme also
specifies the shape and form of the limb.

2. The AER is essential for continued proximodistal outgrowth of the limb. This ectodermal
thickening can initiate reorganization of underlying mesenchyme to produce duplications of distal
tissues

3. The proximodistal patterning of the limb is programmed within the distal cap, which includes the
AER and subjacent mesenchyme and is independent of proximally located tissues

4. Caudal limb mesenchyme can initiate a reorganization of adjacent limb mesenchyme and
subsequently, cause the formation of a new AER and development of a complete supernumerary
limb. Any extra limb formed will develop with its caudal margin adjacent to the grafted caudal
mesenchyme. This region of mesenchyme has been called the zone of polarizing activity (ZPA).
► The skeleton of the limbs is
formed as a hyaline cartilage
precursor ossifies.
► During the seventh and
the eighth weeks of
human development the
digits of the hand
become apparent.

► At the beginning of the fetal period, touch pads are prominent

features of the hands and feet.

► As the hand develops, webs that

are present between the
outgrowing digits must regress.

► Development of
the feet is like that of
the hands, but in the
human it starts
approximately 3 -4 days
later.
 ► The nails of the
fingers and toes first appear
as thickenings of the
epidermis called the primary
nail fields. The position of the
developing nails is evident in
this 64 day hand and foot.

APPENDICULAR MALFORMATIONS

► LIMB REDUCTIONS (melos= limb; dactylos=digits)

1. Amelia (a=lack of)- complete absence of limb

2. Ectromelia- partial or complete absence of a limb or its parts

3. Hemimelia- absence of the half of one or more segments of a limb (e.g. radial hemimelia- no
radius)

4. Meromelia- absence of part of a limb (e.g. crural meromelia- absence of tibia and fibula)

5. Micromelia- a limb that is reduced in size, smaller than normal but all its components or parts are
present

6. Phocomelia (phoco=seal)- absence or reduction of one or more proximal limb segments, often
accompanied by abnormalities of other parts of the limb

7. Syndactyly- fused digits

8. Bradydactyly- shortened digits

9. Ectrodactyly- absence of one or more digits

AMELIA

► Calf body born without legs that

lived several days.

► Of course, one or all limbs may be

found absent. Some proximal
portions of bone may be present
inside the skin areas.
 ► Congenital defect and drugs may be
one cause.

► LIMB DUPLICATIONS

1. Polydactyly- the presence of one or more extra digits. This is common in pigs and cats

2. Notomelia (notos=back)- refers to a limb growing from the back of the animal

3. Perineomelia- occurs when the ectopic limb projects from the perineum

► LIMB AND JOINT DEFORMITIES

1. Arthrogryposis- means crooked limb. It is a deformity of the limb characterized by curvature, or

retention of a joint in a flexed or extended position. Congenital.

2. Hip dysplasia- is an inherited condition usually associated with large, muscular breeds of dogs. It
is characterized by abnormal maturation of the hip joint. Associated frequently with GS and St.
Bernards.

Hip dysplasia

► Too much protein, too much energy, too much

calcium. This slide series is from a study to
investigate the etiology and pathogenesis of a
variety of skeletal diseases occurring in
growing dogs of large-sized breeds.
Subacute canine hip dysplasia

► The fibrocartilage rim tissue is

thickened, the femoral head articular
cartilage is thinned allowing the dark
underlying bone to be easily seen and
some excess connective tissue of
femoral neck. A fourth common
finding of eburnation of the cavity is
not present here.