1. Neuroembryology as a Process of Pattern Formation
PSC 113
Jeff Schank

2. 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
Migration
Differentiation
Connectivity
Selective Survival

3. The Development of Brains
Today, we will focus on how the brain develops as a self-organizing process
Self-organization is a process in which components (e.g., cells) interact in relatively simple ways to generated complex patterns of organization and structure.
Key features of self-organization are that
The parts do not have a “blue print” or “instruction book” for how they should organize
There is no overall controlling element directing the organization
Complex patterns can emerge from local interactions with other cells and physicochemical properties of their substrate and context

4. 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?

5. Four Causes
Composition
Proximate Cause
Organization
Function

6. Pattern Formation and Self-Organization: Cellular slime molds

7. Dictystelium Discoideum
Aggregation when starving
Spiral waves via cAMP
Slug stage
Fruiting bodies

8. Embryonic Development

9. 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)

10. 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

11. Cell proliferation
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

12. Principles of Pattern Formation in Brains
Migration
After cell division (mitosis), cells (neuroblasts) that will become neurons are in many respects like the amoebae
To fully develop as specific types of neurons, they must first migrate and aggregate at various locations in the developing brain
Like free-living 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

13. Migration and Radial Glial Cells
Radial glial (quick introduction to glial cells, also see) 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)

14. Migration and Radial Glial Cells

15. Differentiation
After the amoebae like neuroblasts reach a destination in the developing nervous system they begin to differentiate into neurons and glia cells

16. 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

17. Selective Survival

18. Summary Animation Relating Development to the Adult Brain