neuroembryology as a process of pattern formation psc 113 jeff schank
TRANSCRIPT
Neuroembryology as a Process of Pattern Formation
PSC 113Jeff 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– 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 Self-Organization: Cellular slime molds
Dictystelium Discoideum
Aggregation when starving
Spiral waves via cAMP
Fruiting bodies
Slug stage
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
• 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)
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.
