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Ectodermal Derivatives:
Neurulation
Gilbert - Chapter 12 pp. 373-380
Today’s Goals
• Conclude Unit 2 - Cleavage and Gastrulation
• Overview of Germ Layer Derivatives/Body
Plan of Vertebrates
• Identify Derivatives of the Ectoderm, and
Neural Ectoderm
• Define Neurulation
• Define Primary versus Secondary Neurulation
• Identify different mechanism of Neurulation in
mammals
• Define “Neural Crest” & identify the adult
structures formed by these cells
Ectoderm
• Surface Ectoderm:
– Epidermis, hair, nails, olfactory epithelium, mouth
epithelium, tooth enamel, lens, cornea
• Neural Crest:
– PNS (sympathetic and parasympathetic), adrenal
medulla, melanocytes, facial cartilage, dentine of
teeth
• Neural Tube:
– Brain, neural pituitary, spinal cord, motor neurons,
retina
Neurulation
• During gastrulation, a population of the
dorsal ectoderm is specified to become
neural ectoderm
– Involves signals: Noggin, chordin, follistatin
– Cells become columnar in their
appearance: Neural plate
– The neural plate will be induced to form a
hollow neural tube = spinal cord, brain, etc.
Formation of the Neural Tube
• 2 mechanisms
• Primary Neurulation
– Cells that flank neural plate induce the neural
plate to proliferate, invaginate, pinch off to form
neural tube
• Secondary Neurulation
– Mesenchyme cells of the ectoderm coalesce to
form a solid cord
– Cord then hollows
– This happens further posteriorly
Primary Neurulation
• Divides the ectoderm into 3 populations
– Neural tube, overlying ectoderm, neural crest
• Edges of neural plate thicken
– Move up to form neural folds
– Between folds, neural groove forms
– Forms the midline of the embryo
• Neural folds come together at midline
– Fuse to form neural tube
– Neural crest cells migrate out of dorsal-most
neural tube
Primary Neurulation
• The neural plate is induced to form by
signals from the underlying mesoderm
(notochord)
• Occurs in a rostro-caudal (anteriorposterior) direction
Neural Tube Closure:
Xenopus Model
• Neural tube separates from surrounding
ectoderm and seals to form hollow tube
– Mediated by expression of adhesion
molecules
– N-cadherin and N-CAM are expressed in
neural plate
– E-cadherin is expressed in remaining
ectoderm
– Thus, surface ectoderm and neural plate
can’t adhere to each other
Neural Tube Closure:
Xenopus model
• If N-cadherin is overexpressed in the
surrounding surface ectoderm, neural
tube closure is impeded
– This is achieved by injecting N-cadherin
mRNA into the embryo at the 2-cell stage
Neurulation in Mammals
• Neural tube closes in several places
along axis (not in A to P direction)
• If any one of those closures fails, neural
defects result
Mammalian Neural Tube
defects
• Spina Bifida
– Posterior Neural tube does not fuse
– Spinal cord remains exposed
• Anencephaly
– Anterior Neural tube does not fuse
– Forebrain ceases to develop
– Lethal
• Occur in 1 of 500 births in humans
• Preventable through diet (over 50%)
– Folic Acid
Secondary Neurulation
• Mesenchyme cells condense to form
solid medullary cord
• Cord hollows out
• This occurs in the posterior end of the
embryo (lumbar, tail regions)
Neural Crest
• Originate in dorsal neural tube
• Migrate extensively to populate the
body with a variety of cell types
– Neurons, glia, adrenal medulla, pigment
cells of the skin (melanocytes), skeletal
components of head
Neural Crest Formation
• Neural crest cells form at the junction of
the neural plate and the epidermal
ectoderm
– At the boundary, cells are induced to
express neural crest specific transcription
factors: Slug, FoxD3
Slug and FoxD3 in Neural
Crest Formation
• FoxD3
– If inhibited, no neural crest cells form
– Thus, necessary for neural crest
specification
• Slug
– If inhibited, neural crest cells cannot
migrate
– Thus, necessary for neural crest migration
Neural Crest: 4 domains
• Cranial (cephalic) neural crest
– Cartilage, bone, cranial neurons, glia and connective tissues
of the face, bones of middle ear, jaw, tooth primordia
• Trunk neural crest
– Dorsal root ganglia and sensory neurons, sympathetic
ganglia, melanocytes - ALL pigment cells of body!
• Vagal and sacral neural crest
– Parasympathetic nerves of gut
• Cardiac neural crest
– Melanocytes, neurons, division between aorta & pulmonary
artery
SO Complex
• You could take a whole course on
developmental neurobiology
• We can’t even scratch the surface in
this class!
But wait!. . . .
• Neural crest cells are individual migrating cells Difficult to see in the embryo
• How did scientists find out where they were located,
and what they became later on?
• Ex. Nicole Le Douarin and the Quail-Chick Chimera
• http://www.sdbonline.org/archive/dbcinema/ledouarin/
ledouarin.html - anchor
Example of a
Quail-Chick
Chimera Not Le
Douarin, Not
Neural crest,
but somite