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 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

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? – 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

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

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

7. Embryonic Development

8. 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)

9. Neurulation A groove forms along the anterior-posterior axis of the ectodermgroove forms 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 systemneural tube 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 ganglianeural tube formation

10. 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

11. 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 directionmigrating neuroblastspull the rest of the cell – As with Dictyostelium amoebae, local physical and chemotaxic interactions among neuroblasts and substrate are criticalDictyostelium amoebae

12. Migration and Radial Glial Cells Radial glial (quick introduction to glial cells) cells provide one mechanism by which migrating cells move to specific locationsquick introduction to glial cells 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" micereeler In humans Neuronal Migration Disorders have been identified such as Subcortical band heterotopia (video)Neuronal Migration Disorders Subcortical band heterotopia video

13. Migration and Radial Glial Cells

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

15. 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 cellsgrowth cone234 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

16. Selective Survival

17. Summary Animation Short summary animation of brain development. Note equivalence between connectivity and synaptogenesis and the equivalence between selective survival and synaptic pruning.