Lecture 4

What are the three types of neurulation discussed in class?

Primary, Secondary, and Junctional neurulation.

What is primary neurulation?

Formation of the neural tube from the neural plate; ectoderm thickens to form a neural plate, which then folds to create the neural tube.

What is secondary neurulation?

Condensation and canalization at the tail bud forming a medullary cord that develops into a tube.

What is junctional neurulation?

Merging of the primary and secondary neural tubes, where the top half undergoes primary neurulation and the cells in neural groove form connection to medullary cord

What is exencephaly and anencephaly

Exencephaly - Failure to close the neural tube at the 2/3 points rostral end, Anencephaly - Exposed neural tissue is degraded and no survival

What is craniorachischisis?

Failure to initiate closure at the cervical-hindbrain boundary, resulting in exposed neural tissue along the back and head.

What is spina bifida/myelomeningocele?

A defect where a localized area of the neural tube did not close, forming a fluid-filled sac at the lesion site.

What are some challenges faced by individuals with myelomeningocele?

Reduced life expectancy, neurological problems, orthopedic issues, and lack of bladder control.

What is Arnold Chiari II malformation?

A condition characterized by a low lying fourth ventricle and displaced cerebellum, often associated with myelomeningocele.

What is the two-hit hypothesis for neurological disability in myelomeningocele?

First hit: failure to close leads to inadequate neuron development; Second hit: neurodegeneration due to exposure to neurotoxic substances.

How does dietary folate relate to neural tube defects?

Folate supplementation decreases the incidence of neural tube defects; poor dietary intake of folate is a predisposing environmental factor.

What were the finidings of MOMS trial

in utero repair was more effective at preventing Arnold Chiari malformation and more of the patients were able to walk independently
surgery side effect - weakening of uterus (complications during birth)

What is the difference between a complex and a mendelian trait?

• complex: determined by combined effect of multiple genetic variants of low or intermediate impact, plus strong environmental component

• Mendelian: determined by high impact genetic variants in single gene

What are the purposes of the folate cycle and the methionine cycle?

• Folate cycle produces purines

• Methionine cycle produces SAM (universal methyl donor )

• Both are critical for DNA replication, RNA transcription, DNA and protein methylation

  • determines which genes will be expressed or silenced

What methods have been used to prevent neural tube defects at the population level?

- Educational efforts to encourage people to take folate supplements

- Mail free folic acid vitamins

- Supplement food supply by adding folate to staple item (e.g. flour)