Important Process for the Normal Regulation of Organogenesis and Morphogenesis During Development: Apoptosis
Both respiratory and musculoskeletal systems carry out specific roles. It is only with the formation of these organs which the different roles can be carried out. The formation of these systems will be discussed also the role of apoptosis in the development of these systems. Apoptosis is cell death and is important in the normal regulation of organogenesis and morphogenesis during development.
Lung development is described within five stages. These are: embryonic, pseudo glandular, canalicular, saccular and alveolar. Development of the respiratory system is from the fourth week of gestation. Development of the respiratory system includes both the lungs and conducting pathways from which the trachea, bronchi and bronchioles form.
The outgrowth of the foregut called the respiratory diverticulum marks the origins of the lungs and occurs at the embryonic stage. This shares an opening with the gut at the start however two ridges form which separate out the oesophagus and trachea in the following stage. In this stage interactions between the germ layers occur and cause the mesoderm to develop into cartilage and smooth muscle. The pseudo glandular stage occurs from 6- 16 weeks in humans. Cartilage and smooth muscle cells start to form on the walls of the bronchi. Furthermore, pneumocytes surface which is lung-specific type II alveolar cells. Producing surfactant and by the end of this stage, the respiratory tree is formed. The canalicular stage occurs from 17 to 24 weeks at which the respiratory parts of the lung develop. Type I alveolar cells develop via the process of the ducts lumen widening causing epithelial cells to flatten. The saccular stage occurs from week 25 to birth, and the development of respiratory parts of the lungs are still forming. Type II alveolar cells form creating alveolar stability which will prevent the alveoli from collapsing throughout the expiration mechanism.
Apoptosis is required in lung development as Yeganeh et al investigated cell death is required as its inhibition reduces lung branching this was found in vitro. Apoptosis is required to remove excess mesenchymal cells. This is in order to thin the lung surface to provide space for the airways and air sacs to develop. This was found in both embryonic and pseudo glandular stages allowing room for the growth of the lung bud and a higher rate of apoptosis found in the later stage as more branching of lung development occurs then. Apoptosis at the canicular stage occurs by thinning of the alveolar septa to increase air spaces and in increase in gas exchange. Epithelial cell apoptosis is evident at the saccular stage and types 2 alveolar cell apoptosis which contributes to lung remodelling later through gestation. It is with apoptosis occurring that gas exchange is possible efficiently.
Within the musculoskeletal system, the limbs occur from week 4 to the adult period. A standard limb has three parts: stylopod, zeugopod and autopod. With the mesoderm cells proliferating the limb bud forms and it is known the upper bud forms at the level of C5-t1 and the lower bugs are apparent on the level of L1-L5. It is known that limb buds are described in three parts. The paraxial mesoderm which provides dermis and muscle. The lateral plate provides bone and blood vessels and the neural crest is known of it role with melanocytes and the peripheral nervous system (PNS). After reciprocal exchanges of the mesoderm and ectoderm, a ridge is formed called the apical ectodermal ridge (AER). Underneath that ridge lie dividing cells that act rapidly and is the proliferating zone. Without the AER distal outgrowth of the limb would not occur and hence is vital for the proximal-distal axis.
Mesenchymal cells in the down region on the limb bud make up the anterior-posterior axis of the limb. This is known as the zone of polarising activity (ZPA). This zone releases sonic hedgehog (SHH) which causes digit formation. Digit formation occurs at between weeks 6 -7. The mesenchymal cells condense which forms a long thick ending. It is only with localised cell death that five digital rays are apparent. Bones are developed via somite derived from paraxial mesoderm, this develops into vertebral and bones.
As discussed previously localised cell death is needed for digits to be separate and this is only achieved with programmed cell death. This eliminates cells that are not required during embryogenesis. Chen and Zhao have discussed that there are many signalling factors and genes related to the control of cell death in limb buds. Abnormalities apparent in digit separation is dependent on BMP signalling and the release of SHH from the ZPA. BMP4, a BMP derivative was the first evidence showing the regulation of apoptosis of neural crest cells. This result in syndactyly. Apoptosis can be regulated by environmental conditions similarly can be regulated by the interactions between epithelial and mesenchymal. It was found by Saunders et al that the AER or ectoderm are vital in apoptosis and by removing small layer apoptosis will be inhibited. This shows the interactions between epithelial and mesenchymal are key for apoptosis.
The different forms of apoptosis for lungs and limbs are specific to each structure. For example, apoptosis in the lungs means that the maximum amount of gases can be exchanged and in limb and bone structure movements such as grasping of objects and movement. A similarity of apoptosis in both structures is the interactions of epithelial and mesenchymal which are both vital for apoptosis to take place. Without this interaction, apoptosis would not take place and lungs and limbs both would not adapt to the best of their function. The difference of the role of apoptosis is the outcome if apoptosis is not initiated. Abnormalities in limbs that would occur are amelia this is the absence of a whole limb. This is caused by an early loss of Fgf signalling. When extra digits form called polydactyly is caused by upregulation of the SHH pathway. Abnormalities that form in the lungs due to no apoptosis is newborn respiratory distress syndrome (NRDS) this occurs when a baby’s lung is not fully developed and causes breathing difficulties. Chronic lung disease can occur when air sacs are not fully developed to allow the maximum exchange of gases. The differences in apoptosis are vital in the musculoskeletal, respiratory and other systems such as the nervous system. This allows that system to function to the best of its ability.
