Mechanisms of Disease During the Embryogenesis

Question 1

Describe the complexity involved in embryonic development

Answer 1

1) Fertilisation and Formation of the Zygote:

• fusion of sperm and egg cells during fertilization, creating a single cell known as the zygote, which is a single cell with full genetic potential

2) Cleavage:

• Series of rapid cell divisions without cell growth, leading to an increase in the cell number, divided into smaller cells called blastomeres without an increase in the overall size of the embryo
• This results in a multicellular structure ‘ball of cells’ known as a blastula, which consists of an outer layer of cells surrounding a fluid-filled cavity

3) Gastrulation:

• A phase during which the blastula undergoes significant reorganisation to form a structure known as the gastrula
• This process involves cell migration and differentiation leading to the formation of three germ layers: the ectoderm, mesoderm, and endoderm, which will give rise to all tissues and organs of the organism

4) Neurulation:

• Neurulation is the process by which the neural tube forms from the ectoderm, the outermost germ layer
• The neural tube will eventually develop into the central nervous system (brain and spinal cord).
• disruptions in neurulation can lead to severe congenital abnormalities like neural tube defects

5) Somitogenesis:

• the process by which somites form
• Somites are blocks of mesoderm located on either side of the neural tube in the developing vertebrate embryo
• These somites will give rise to important structures such as the vertebral column, dermis of the skin, and skeletal muscle

6) Organogenesis:

• The germ layers develop into the different organs of the organism.
• E.g. the ectoderm forms the nervous system and skin
• the mesoderm forms muscle, bone, and blood
• the endoderm forms the lining of the digestive tract and associated organs
• The homeotic (Hox) genes are regulators of organogenesis, encodes transcription factors

7) Morphogenesis:

• refers to the physical process that gives an organism its shape
• It involves the coordination of cell division, differentiation, and changes in cell shape and position
• These changes are controlled by regulatory genes, which are responsible for the spatial and temporal patterns of embryonic development

Gene Regulatory Networks (GRNs):

• complex networks of genes and their regulatory proteins (transcription factors) that interact to control the expression of genes in a coordinated manner
• The GRNs are responsible for the timing, location, and level of gene expression during development

Question 2

Describe and explain the difference between genetic and environmental causes for congenital disease

Answer 2

Genetic Causes:

1) Single-Gene Disorders:

• result from mutations in a single gene and follow Mendelian inheritance patterns
• They can be dominant (like Huntington’s disease), recessive (like cystic fibrosis), or X-linked (like haemophilia)

2) Chromosomal Disorders:

• caused by an abnormal number of chromosomes or structural changes in chromosomes
• E.g. Down syndrome is caused by having an extra copy of chromosome 21 (trisomy 21)

3) Multifactorial Inheritance Disorders:

• involve a combination of small variations in genes, often in interaction with environmental factors
• E.g. Cleft lip and palate

Environmental Causes:

1) Infections:

• Certain infections in the mother can lead to congenital diseases in the foetus
• E.g. rubella infection during pregnancy can cause heart defects, hearing loss

2) Drugs and Chemicals:

• Some medications and chemicals can cause congenital abnormalities if taken or encountered during pregnancy
• E.g. thalidomide, a drug originally used to treat morning sickness, caused severe limb abnormalities

3) Radiation:

• Exposure to radiation during pregnancy can lead to congenital abnormalities

Question 3

Identify examples of birth defects and relate them to a specific developmental process

Answer 3

1) Neural Tube Defects (NTDs):

• NTDs, including anencephaly and spina bifida, are severe birth defects of the brain and spine that occur due to abnormal neural tube closure
• The neural tube forms early in development (around the third and fourth weeks of embryogenesis) and normally closes to form the brain and spinal cord. If the tube doesn’t close properly, it can lead to NTDs
• E.g. anencephaly results from failure of the anterior (rostral) neural tube to close, leading to a lack of a major portion of the brain, skull, and scalp

2) Congenital Heart Defects (CHDs):

• occur due to disruptions in the complicated process of heart development
• E.g. Tetralogy of Fallot is a CHD involving four anatomical abnormalities of the heart and is caused by a defect in the development of the outflow tract of the heart

3) Cleft Lip and/or Cleft Palate:

• occur when the processes of facial development, specifically the fusion of the facial processes, don’t happen correctly
• The lip usually forms by about the 7th week of pregnancy and the palate by around the 10th week
• If the structures that form the upper lip or palate fail to join together, clefts can occur

4) Down Syndrome (Trisomy 21):

• caused by the presence of an extra full or partial copy of chromosome 21

5) Polydactyly:

• During limb development, the apical ectodermal ridge (AER) at the tip of the limb bud plays a crucial role in outgrowth and patterning of the limb along its proximodistal (shoulder to fingers/toes) axis
• Within the limb bud, there is also a zone of polarizing activity (ZPA) that produces signals to specify the anteroposterior (thumb to little finger) axis of the limb
• If these areas of the limb bud behave abnormally or receive incorrect genetic signals, the result can be an abnormal number of digits