Limb Development PDF

Embryology Development Of the Limbs - Objectives: -To demonstrate, understanding the limb development during pregnancy. -What are the important areas that signaled to developed a normal limb, and the effect of these signals to define the anatomical structures in relation to their...

Embryology Development Of the Limbs - Objectives: -To demonstrate, understanding the limb development during pregnancy. -What are the important areas that signaled to developed a normal limb, and the effect of these signals to define the anatomical structures in relation to their position. -How Bones, Muscles and nerve developed during these processes. -The positional changes (rotation) of limb during the development. -What limb developmental defect might occur. Limb Development Limb development begins with the activation of a group of mesenchymal cells from the somatic layer of lateral mesoderm. Limb buds first appear as elevations (swelling) of the ventrolateral body wall toward the end of the 4 the week (28 days). Limb buds is covered by thick band of ectoderm. The upper limb buds are visible by day 26 or 27 and the lower limb buds are appearing a day or 2 later. Limb buds elongate by the proliferation of the mesenchyme. The upper limb buds appear low on the embryo’s trunk because of the early development of the cranial half of the embryo. The upper limb buds develop opposite the caudal cervical segments and the lower limb buds form opposite the lumbar and upper sacral segments. At 32 days, the upper limb buds are paddle- shaped and the lower limb buds are flipper- like.  The limb bud appears as an elevation on the ventrolateral body wall resulting from proliferation of mesenchyme of the somatic layer of the lateral mesoderm. Each limb bud is surrounded by an area of ectoderm. Limb buds structure the limb buds are formed of: -Mesenchymal core derived from the parietal (somatic) layer of lateral plate mesoderm it forms the bones and connective tissues of the limb. paraxial mesoderm which forms muscules. -The mesenchymal core is covered by a layer of cuboidal ectoderm.  Molecular Regulation of Limb Development 1.Positioning of the limbs along the craniocaudal axis in the flank regions of the embryo is regulated by the HOX genes (HOXB8). HOX genes in general play a critical role in patterning the bones of the limbs. 2-Specification of the forelimb is regulated by: -The transcription factor TBX5. specification of the hind limb is regulated by: -TBX4. 3. Limb outgrowth is initiated by fibroblast growth factor (FGF) 10 secreted by lateral plate mesoderm in the limb—forming regions. AXIS OF LIMBS Positioning of the limbs along the craniocaudal axis in the flank regions of the embryo is regulated by the HOX genes expressed along this axis. 1.Proximodistal: limb grows from humerus to fingers. 2. Anteroposterior (craniocaudal): limb grows from thumb to little finger. 3. Dorsoventral: differentiation of the extensor and flexor compartments. 1.Proximodistal axis Apical Ectodermal Ridge (AER) is essential for limb bud development in proximal to distal axis. At the tip of each limb bud, the ectoderm is thickened to form the AER. This ridge has an inducing effect on underlying mesenchyme causing cells to proliferation. As cells are proliferating the limb bud grows distally and form progress zone. The earliest mesenchyme (the oldest) form base and proximal cells differentiate into cartilage. FGFs keep cells in the progress zone proliferating and prevent their differentiation. As the limb grows, cells at the back of the progress zone are moved farther away from the influence of FGFs secreted by the AER. As FGF concentrations decrease around these cells, they begin to form condensing mesenchyme, the first step in differentiating into cartilage. Anteroposterior axis Anteroposterior axis is control by zone of polarizing activity (ZPA). The master gene for this regulation is sonic hedgehog(SHH) secreted by (ZPA). The signal from the polarizing region appears to control both digit number and digit pattern. Digits appear in the proper order, with the thumb on the radial (anterior) side. As the limb grows, the ZPA moves distal ward to remain in proximity to the posterior border of the AER. Misexpression of ZPA or SHH in the anterior margin of a limb results in a mirror image duplication of limb structures. (polydactily)  Dorsoventral axis Dorsoventral (back of the hands versus the palms) is regulated by genes expressed in the dorsal and ventral ectoderm. -Bone patterning is regulated by a complex pattern of overlapping Hox gene expression, bmp and WNT-7 gene. -They also control the pattern of muscles, orientation of the joints and eventual characteristic differentiation of the epidermis. development of each limb proceeds proximodistally into its three components: Stylopod (humerus and femur). Zeugopod (radius/ulna and tibia/fibula). Autopod (carpels, metacarpals, digits/tarsals, digits/metatarsals).  Segmentation The proximal part of the limb begins to differentiate first followed by the distal part. The distal end flatten into a paddle like plate to form hand and foot plates. It is separated by proximal segment by a circular constriction. A second constriction appears and divides the proximal part into two segments. Digit formation Indentations appear in the hand plate. -At 6th week mesenchymal condensation appears as digital rays. -With further development the webs between the fingers regress. -The fingers are separated by each other. Development of the foot is like that of the hand. -Interdigital tissue is removed by programmed cell death(apoptosis) to create 5 separate digits. -Digits continue growing under the influence of the remaining parts of the AER that cover each one.  Limb Musculature -The limb musculature is derived from the myotomes of the somite that migrate into limb. -Muscle cells for the limbs are derived from somites at specific segmental levels. -for the upper limb, these segments are C5-T2; for the hind limb they are L2-S2. -The muscles are arranged into ventral and dorsal muscular mass with respect to axis. -The ventral muscle mass give rise to flexor and pronator in UL and flexor and adductor in LL. - The dorsal muscle mass give rise to extensor group of muscles. Limb Innervation - Upper limb bud appears opposite the caudal cervical spinal segments. Lower limb bud appears opposite the lumbar and sacral spinal segments. Spinal nerves enter the limb bud early in its development. Without this innervation, development stops. Nails Nails develop from nail folds on the tips of the fingers. Nail folds migrate onto the dorsal surface, bringing their nerve supply with them. Dermatomes and Myotomes: Dermatome – Strip of skin supplied by a single spinal nerve Myotome – Muscle/Group of muscles supplied by a single spinal nerve.