Download Neuroembryology as a Process of Pattern Formation

Neuroembryology as a Process of
Pattern Formation
PSC 113
Jeff Schank
Outline
• The Development of Brains
• A Self-Organization Perspective on the
Development of the Nervous System
• Pattern Formation and Self-Organization
– Cellular Slime Molds
• Rules of Pattern Formation in Brains
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Migration
Differentiation
Connectivity
Selective Survival
The Development of Brains
• Today, we will focus on how the brain develops as a complex
process of pattern formation resulting from self-organizing
processes
• For development, self-organization is a process by which
components (e.g., cells) interact in relatively simple ways to create
complicated patterns of organization and structure.
• Key features of self-organization are that
– The parts themselves do not have a “blue print” or “instruction book”
for how they should organize themselves with respect to other parts
– There is no overall controlling element directing the organization
– Instead, complex patterns can emerge from local interactions with
other cells and physicochemical properties of their substrate and
context
A Self-Organization Perspective on the
Development of the Nervous System
• There are many questions that can be asked about how
such a complex system such as a brain emerges during
development:
– How are all of the neurons generated from a single-celled
embryo (i.e. zygote)?
– How do neural cells “know” what type they are to become?
– How do neurons end up in the correct spatial location in the
brain?
– How do specific connections form among neurons?
– How can we get this incredible complexity from so few genes?
• All of these questions and many more have been addressed
since the early 1800s and today they are still one of the
more active areas of study of the nervous systems of
animals
Pattern Formation and SelfOrganization: Cellular slime molds
Dictystelium Discoideum
Aggregation when
starving
Spiral waves via
cAMP
Fruiting bodies
Slug stage
Embryonic Development
Gastrulation in Mammals
• Ectoderm (outer layer; these cells give rise to the nervous system
and skin),
• Mesoderm (middle layer; these cells give rise to the muscle,
skeleton, connective tissue, and cardiovascular and urogenital
systems), and
• Endoderm (inner layer; these cells give rise to the gut and other
internal organs)
Neurulation
• A groove forms along the anterior-posterior axis of the
ectoderm
• Ectodermal cells on either side of this neural groove thicken
and form the neural plate, which lies on the dorsal surface
of the developing embryo
• As the embryo develops, the folds of the neural plate meet
and cover the groove, forming the neural tube from which
will emerge the brain and the spinal cord of the central
nervous system
• During neural tube formation, some cells break away from
the neural plate and move just above the top of the neural
tube, forming the neural crest, which will eventually give
rise to spinal and autonomic ganglia
Cell proliferation
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Cell proliferation begins at this point along the neural tube resulting in distinct specializations along
the rostral-caudal axis
Cell proliferation gives rise to specific brain divisions: prosencephalon, mesencephelon, and
rhombencephelon
These three structures eventually become the cerebral hemispheres, the midbrain, and the brain
stem, respectively
Principles of Pattern Formation in
Brains
• Migration
– After cell division (mitosis), cells that become neurons are in
many respects like the amoebae
– These cells are called neuroblasts and lack many of the
characteristics of mature neurons (e.g., shape of the cell body,
and dendritic and axonal branches)
– To fully develop as specific types of neurons, they must first
migrate and aggregate at various locations in the developing
brain
– Like the amoebae, the migrating neuroblasts extend part
themselves in one direction and pull the rest of the cell in that
direction
– As with Dictyostelium amoebae, local physical and chemotaxic
interactions among neuroblasts and substrate are critical
Migration and Radial Glial Cells
• Radial glial (quick introduction to glial cells) cells
provide one mechanism by which migrating cells move
to specific locations
• Many waves of migrating cells move up “rope” ladders
• For normal development to occur, earlier migrating
cells must “get off” at the right place or pile ups can
occur
• Failure to do so can lead to sever developmental
abnormalities in development such as "reeler" and
"staggerer" mice
• In humans Neuronal Migration Disorders have been
identified such as Subcortical band heterotopia (video)
Migration and Radial Glial Cells
Differentiation
• After the amoebae like neuroblasts reach a destination
in the developing nervous system they begin to
differentiate into neurons and glia cells
Connectivity
• A functional brain are the patterns of connections formed by the
axons and dendrites of developing neurons
• Axons and dendrites move towards targets as neurites
• The growth cone (video 2, 3, 4) is at the tip of neurites and it
responds to cues and interactions with its local environment. In
much the same way as migrating cells
• Nerve growth factor (NGF) can guide the direction of the neural
growth cone just as cAMP guides the movement of Dictyostelium
amoebae
• Neurites move by finger-like extensions from the growth cones,
which adhere to the substrate and drag the neurite along
• Just as with neural selectivity and death, dendrites can be increased
or decreased by the gradients of NGF surrounding a cell
Selective Survival
Summary Animation
Short summary animation of brain development. Note equivalence
between connectivity and synaptogenesis and the equivalence
between selective survival and synaptic pruning.