DEVBIOL

• Limb growth and development involves the appendicular skeletal components, including the shoulder and pectoral girdles, and the axial skeletal components, including the spine, ribs, and sternum.
• At the end of the fourth week of development, limb buds become visible as outpockets from the ventral body wall.
• The forelimb appears first followed by the hindlimb, appearing 2 days later.
• The final separation of the digits is achieved by additional apoptosis in the interdigital spaces.
• Programmed cell death, also known as apoptosis, occurs when the digit separation process is complete.
• Congenital absence of the radius or digital defects, such as absent thumb or polydactyly, can be considered as an indication for other malformations.
• Many digital defects occur that are related to these patterns of cell death, including polydactyly, syndactyly, and clefts.
• The limb buds consist of a mesodermal core derived from the parietal (somatic) layer of lateral plate mesoderm.
• In most cases, dominant mutations in the COL1A1 or COL1A2 genes are involved in the production of type I collagen, causing the abnormalities.
• Affected individuals are usually tall and slender with long thin limbs and a long thin face.
• Other characteristics of osteogenesis imperfecta include stunted growth, short stature, and scoliosis.
• Osteogenesis imperfecta involves the hands or feet or both.
• Several types of osteogenesis imperfecta range from mildly increased frequency of fractures to a severe form that is lethal in the neonatal period.
• Arthrogryposis or congenital joint contractures usually involve more than one joint and may be caused by neurological defects such as spina bifida or hydrocephalus.
• The limb buds undergo a process of cell proliferation and differentiation, resulting in the formation of the bones.
• Anomotic bands may cause ring constrictions and amputations of the limbs.
• The origin of the bands is not clear, but they present adhesions between the amniotic membrane and affected structures in the fetus.
• Individuals with synostosis in one or more cranial sutures, absence of the radius, and other defects may have drbfoot.
• Other investigators believe that bands originate or re-enter the amniotic chamber at the time of birth and surround part of the fetus.
• Drbfoot is often caused by constraint in utero from too little amniotic fluid (oligohydramniosc).
• Transverse limb deficiency, which may be caused by disruptions to the AER or to vascular abnormalities, is a type of limb defect.
• Congenital abnormalities such as craniosynostosis, tosis syndrome, and other disorders can lead to drbfoot.
• The limb buds are influenced by the apical ectodermal ridge (AER), which exerts an inductive influence on adjacent cells, causing them to remain as a population of undifferentiated, rapidly proliferating cells, forming the progress zone.
• The external view of a chick embryo limb at high magnification shows the ectoderm and the spinal cord at the tip of the limb called the AER.
• Upper limb buds lie opposite to the lower five cervical and upper thoracic segments.
• A single muscle may be formed from more than one original segment.
• The resulting complex pattern of muscles is determined by connective tissue derived from lateral plate mesoderm.
• In the AER, the connective tissue forms a separate ridge for each digit.
• In humans, the AER corresponds to the area of the hand between the thumb and the index finger.
• In humans, this occurs during the fifth week of development.
• By 56 days, digit separation is complete.
• At 14 days, separation of the digits occurs in the interdigital spaces.
• Limb musculature is derived from dorsal lateral cells of the somites and migrates into the limb to form muscles.
• Compound muscle components are scrambled according to the somites from which they are derived.
• As growth occurs, neurochemicals at the permissive end of the progression zone become further away from the ridge and influence and guide their division rates and differentiation.
• The AER is established at the distal tip of the limbs.
• After the ridge is established, it expresses FGF4 and FGF8, which maintains the rapidly proliferating population of mesoderm cells adjacent to the ridge.
• Positioning along the craniocaudal axis is constant.
• Formation of the bone is assisted by the presence of Enrailed-1 in ventral cerebral cortex, because the gene represses expression of R1 and induces expression of Enrailed-1.
• Once limb outgrowth is initiated, bone morphogenetic proteins (BMPs) expressed in ventral ectoderm are induced for the formation of the AER by signaling through the Hox box grin.