Embryonic Brain Development and Nervous System Structure

• ectoderm


  skin (epidermis) and nervous system

  • outer germ layer
• mesoderm

  mostly muscle and connective tissues

  • middle germ layer
  • will condense to form the notochord
• endoderm


  all the other stuff, like most organs

  • inner germ layer
• gastrulation


  rearrangement of cells in the developing organism to form the germ layers
• neurulation


  process by which the region of the ectoderm that will become the nervous system involutes

  • primary
• gastrulation and neurulation

  • first, the cells that will become the mesoderm move to the inside of the embryo
  • will condense to form the notochord by 16-18 days post fertilization
  • next, the region of ectoderm overlaying the mesoderm (the neural plate) will involute to form the neural tube
• what makes the neural plate the neural plate?

  signals from the underlying mesoderm/notochord act on this region of tissue to specify it to be neurally fated and not epidermally fated like the rest of the ectoderm
• gastrulation, and the formation of the mesoderm, is the single most important event in development

  • no gastrulation -> no mesoderm -> no notochord -> no molecular signals to support the formation of neural tissue
• mammalian neurulation: primitive streak

  • groove along the midline where cells migrate through
  • mesodermal cells migrate in first -> condense to form the notochord inside along the midline
• mammalian neurulation: neural plate

  • ectodermal cells that overlay the notochord; receive molecular signal to become neurally fated
  • involute to form neural tube
• mammalian neurulation: neural crest

  • celsl at the very border between the neural plate and the rest of the ectoderm
  • break away from the ectoderm and neural tube
  • will eventually form many things including sensory/peripheral neurons and some glia
• the formation of the neural tube has distinct migratory routes. each route will have the neural crest cells exposed to different chemical cues which will control the types of cells they differentiate into
• mammalian neurulation: day 22

  • by day 22 post fertilization, the neural tube is closed and the neural crest cells have broken free
  • the neural tube will differentiate along the anterior/posterior axis and the dorsal/ventral axis
  • the dorsal portion of the neural tube is the roofplate and the ventral portion of the neural tube is the floorplate
  • different kinds of cells will form along the dorsal/ventral and anterior/posterior axes of the neural tube
• neurulation:

  • the neural tube, which contains the majority of the cells that are permitted to become neural, is formed and closed by the end of the first month after fertilization
  • neural tube closes starting in the middle and extends to the anterior and posterior
  • anterior neuropore: at brain end; should close by day 26
  • posterior neuropore: at tail end; should close by day 28
• anencephaly


  failure to develop a brain

  • often a result of the anterior neuropore not closing
  • fatal
• iniencephaly

  regions of skull and cervical spine fail to develop along with brain structures

  • anterior neural tube defect
  • fatal
• encephalocele


  brain bulges through sac like opening in the skull

  • anterior neural tube defect
  • almost always fatal
• craniorachischisis

  exposed brain and spinal cord

  • fatal
  • extremely incomplete closure of neural tube
• spina bifida

  incomplete closing of the backbone and membranes around the spinal cord

  • 28th day of gestation (posterior neuropore)
  • most common location is the lower back, but can occur in the middle back or neck
• spina bifida: myelomeningocele

  • most serious type of spina bifida
  • sac of fluid comes through an opening in the baby's back
  • part of the spinal cord and nerves are in the sac and are damaged
  • causes moderate to sever disabilities, such as problems affecting bathroom usage, loss of feeling in the person's legs/feet and not being able to move the legs
• spina bifida: meningocele

  • sac of fluid comes through and opening in the baby's back, but the spinal cord is not in this sac
  • usually little or no nerve damage. can cause minor disabilities
• spina bifida: occulta

  • mildest type of spina bifida
  • "hidden"
  • small gap in the spine but no opening or sac on the back
  • spinal cord and nerves are usually normal
• the cells are multipotent

  • they are restricted in that they must become some type of neural cell, but they are still open to becoming any type of neural cell
  • early on, most are progenitors who will give rise to more progenitors, neurons and glia
  • expand the nervous system
  • as development progresses, their fates will become restricted
• embryonic stem cells

  taken from pre-gastrulas

  • can become any type of cell in the embryo
  • true stem cells
• neural stem cells

  restricted to becoming cells of the nervous system

  • not true stem cells because they are restricted
• multipotent progenitors 


  cells that can give 'birth' to many different cell types

  • more accurate description of cells in the early neural tube
• holoprosencephaly

  failure of the prosencephalon to develop into two hemispheres; sometimes the result of Sonic Hedgehog (Shh) defects
• retinoic acid exposure

  retinoic acid is anti-anterior/anti-brain; too much retinoic acid during the wrong part of development can lead to loss of forebrain structures
• medulloblastoma


  progenitors keep dividing after they should stop; leads to uncontrolled granule cell proliferation; often a result of a Shh defect
• prosencephalon (forebrain) -> telencephalon -> cerebral cortex, cerebral nuclei (basal ganglia, amygdala, basal forebrain) | lateral ventricles
• prosencephalon (forebrain) -> diencephalon -> thalamus, hypothalamus, retina | third ventricle
• mesencephalon (midbrain) -> superior and inferior colliculi, red nucleus, substantia nigra | cerebral aqueduct
• rhombencephalon (hindbrain) -> metencephalon -> cerebellum, pons | fourth ventricle
• rhombencephalon (hindbrain) -> myelencephalon -> medulla oblongata | fourth ventricle
• spinal cord -> spinal cord | central canal
• telencephalon


  cerebral cortex

  hippocampus

  amygdala

  basal ganglia
• cortical neogenesis

  1. progenitors occupy VZ (ventricular zone)
  2. first neurons exit cell cycle and go to preplate (Cajal-Retzius and subplate)
  3. new neurons (red) migrate along radial glia fibers to form cortical plate
• not all cortical neurons are born locally: GABAergic interneruons
• diencephalon

  thalamus

  hypothalamus

  epithalamus
• brainstem (midbrain and stuff)

  • midbrain
  • substantia nigra
  • colliculi
  • red nucleus
  • VTA
  • pons
  • medulla
  • home of 10 pairs of cranial nerves
  • motor and sensory info highway
  • cardiac and respiratory function