Development general

Question 1

Overview of brain development

Answer 1

• CNS is derived from the ectoderm, the outermost tissue layer of the embryo
• in third week of human embryonic development, the neuroectoderm appears and forms the neural plate along the back of the embryo
• neural plate is source of majority of neurons and glial cells
• by week 4, neural plate wraps itself to create the neural tube, which is filled with CSF
• over development, the anterior part of the neural tube forms three vesicle that become the forebrain, midbrain, and hindbrain
• these three vesicles then further develop into telencephalon, diencephalon, mesencephalon, myelencephalon

—> neural tube gives rise to the brain and spinal cord —> any mutations at this stage can lead to fatal deformities or lifelong disabilities

• walls of neural tube contain stem cells, which drive brain growth as they divide
• gradually some cells stop dividing and differentiate into neurons and glia
• neurons migrate to different parts of the brain and self-organize
• once neurons have reached their positions, they form axons and dendrites to communicate with each other

Question 2

Neural Induction

Answer 2

• during early embryo stages, the ectoderm becomes specified to give rise to the epidermis and the neural plate
• this change from ectoderm to neuro-ectoderm requires signals from the mesoderm:
  
  • mesodermal cells form a layer between the endoderm and ectoderm —> give rise to a structure called notochord
  • ectodermal cells overlying the notochord develop into the neural plate in response to a signal produced by the notochord —> bone morphogenetic proteins are inhibited, which leads to cells expressing proneural genes and forming neural tissue
  • rest of the ectoderm becomes skin —> bone morphogenetic proteins prevents the formation of neural tissue
  • mesoderm converting the overlying ectoderm into neural tissue = neural induction
• when ectodermal cells are cultured in the absence of mesodermal cells, the express neural genes —> suggests that neural differentiation is the default and that BMP need to be present in order to prevent this

Question 3

Patterning and Shh

Answer 3

Neural tube is patterned by sonic hedgehog

• Shh is essential for specification of ventral neuron progenitor domains
• loss of Shh prevents proper specification
• Shh acts a morphogen —> induces cell differentiation dependent on its concentration
  
  • low concentration: interneurons
  • high concentrations: motor neurons

Question 4

Radial Migration

Answer 4

• how neurons migrate from their neural stem cell origion
• radial glial cell
• process:
  
  • first postmitotic cells leave the stem cell niche and migrate outward to form the preplate
  • do this via somal translocation
  • bipolar and attch the leading edge of the process to the pia
  • soma is transported to the pial surface
  • new neurons migrate along radial glial fibres to form the cortical plate
  • each waves of migrating cells travel past their predecessors forming layers in an inside-out matter —> youngest neurons are closest to the surface