Neuroembryology as a Process of PaYern FormaVon Outline The

Outline Neuroembryology as a Process of Pa5ern Forma8on PSC 113 Jeff Schank The Development of Brains • Today, we will focus on how the brain develops as a complex process of pa5ern forma8on resul8ng in large part from self-­‐
organiza8on • For development, self-­‐organiza8on is a process by which components (e.g., cells) interact in rela8vely simple ways to create complicated pa5erns of organiza8on and structure. • Key features of self-­‐organiza8on are that – The parts themselves do not have a “blue print” or “instruc8on book”
for how they should organize themselves with respect to other parts
– There is no overall controlling element direc8ng the organiza8on
– Instead, complex pa5erns can emerge from local interac8ons with
other cells and physicochemical proper8es of their substrate and
context • The Development of Brains
• A Self-­‐Organiza8on Perspec8ve on the
Development of the Nervous System
• Pa5ern Forma8on and Self-­‐Organiza8on
– Cellular Slime Molds
• Rules of Pa5ern Forma8on in Brains
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Migra8on
Differen8a8on
Connec8vity Selec8ve Survival
A Self-­‐Organiza8on Perspec8ve on the Development of the Nervous System • There are many ques8ons 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 spa8al loca8on in the brain? – How do specific connec8ons form among neurons?
– How can we get this incredible complexity from so few genes?
• All of these ques8ons and many more have been addressed
since the early 1800s and today they are s8ll one of the more ac8ve areas of study of the nervous systems of animals 1 Pa5ern Forma8on and Self-­‐
Organiza8on: Cellular slime molds Dictystelium Discoideum Aggrega8on when starving Spiral waves via cAMP Slug stage Frui8ng bodies Embryonic Development and Induc8on Gastrula8on • Ectoderm (outer layer; these cells give rise to the nervous system and skin), • Mesoderm (middle layer; these cells give rise to the muscle,
skeleton, connec8ve 8ssue, and cardiovascular and urogenital
systems), and • Endoderm (inner layer; these cells give rise to the gut and other internal organs) 2 Neurula8on • 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 forma8on, 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 Principles of Pa5ern Forma8on in Brains • Migra8on
– Ader cell division (mitosis), cells that become neurons are in
many respects like the amoebae – These cells are called neuroblasts and lack many of the
characteris8cs of mature neurons (e.g., shape of the cell body, and dendri8c and axonal branches) – To fully develop as specific types of neurons, they must first migrate and aggregate at various loca8ons in the developing brain – Like the amoebae, the migra8ng neuroblasts extend part themselves in one direc8on and pull the rest of the cell in that direc8on – As with Dictyostelium amoebae, local physical and chemotaxic interac8ons among neuroblasts and substrate are cri8cal Cell prolifera8on •
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Cell prolifera8on begins at this point along the neural tube resul8ng in dis8nct specializa8ons along the rostral-­‐caudal axis
Cell prolifera8on gives rise to specific brain divisions: prosencephalon, mesencephelon, and
rhombencephelon
These three structures eventually become the cerebral hemispheres, the midbrain, and the brain stem, respec8vely Migra8on and Radial Glial Cells • radial glial (video 1) cells provide one mechanism by which migra8ng cells move to specific loca8ons • Many waves of migra8ng cells move up “rope” ladders
• For normal development to occur, earlier migra8ng cells must “get off” at the right place or pile ups can
occur • Failure to do so can lead to sever developmental abnormali8es in development such as "reeler" and
"staggerer" mice • In humans Neuronal Migra8on Disorders have been iden8fied such as Subcor8cal band heterotopia (video) 3 Migra8on and Radial Glial Cells Differen8a8on • Ader the amoebae like neuroblasts reach a des8na8on
in the developing nervous system they begin to differen8ate Connec8vity Selec8ve Survival • A func8onal brain are the pa5erns of connec8ons 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 8p of neurites and it responds to cues and interac8ons with its local environment. In
much the same way as migra8ng cells • Nerve growth factor (NGF) can guide the direc8on 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 selec8vity and death, dendrites can be increased
or decreased by the gradients of NGF surrounding a cell 4 Summary Anima8on Short summary anima8on of brain development. Note equivalence between connec8vity and synaptogenesis and the equivalence between selec8ve survival and synap8c pruning. 5