BIOL2051-52 Brain Development & Neural Circuits - I PDF

BIOL2051-52 BRAIN DEVELOPMENT AND CONSTRUCTION OF NEURAL CIRCUITS - I Kif Liakath-Ali, PhD [email protected] www.splicelab.co.uk THE CHALLENGE The human brain contains ~ 100billion neurons, each forming thousands of...

BIOL2051-52 BRAIN DEVELOPMENT AND CONSTRUCTION OF NEURAL CIRCUITS - I Kif Liakath-Ali, PhD [email protected] www.splicelab.co.uk THE CHALLENGE The human brain contains ~ 100billion neurons, each forming thousands of connections ~1quadrillion synapses are formed during development, >50% are eliminated again =1,000,000,000,000,000 Estimates of ≥1 petabyte (=1k TB) storage capacity Q: How does the brain generate the correct number of cells, right types of cells, in the correct place, in time, and assemble them into functional neural circuits? THE CHALLENGE Prof. Tom Jessell – Howard Hughes Holiday Lectures: www.hhmi.org/biointeractive MANY DIFFERENT TYPES OF NEURONS Ramon y Cajal 1899 AND OF GLIA EVERY FUNCTION OF THE NERVOUS SYSTEM - VOLUNTARY OR INVOLUNTARY – IS UNDERPINNED BY A CIRCUIT! sensing changes in the external environment deciding what to do based on instinct and experience responding HOW DOES ONE CELL GIVE RISE TO THE ENTIRE NERVOUS SYSTEM? Aim: To explore the key stages in the development of the nervous system LEARNING OUTCOMES By the end of the three lectures, and following revision of the associated learning material, you should be able to: Describe the processes of neurogenesis, differentiation, migration Describe the process of target innervation Describe the principles of synapse formation and elimination HOW DOES ONE CELL GIVE RISE TO THE ENTIRE NERVOUS SYSTEM? RESOURCES FOR REVISION: Your textbook! Purves: Neuroscience. Chapters on early brain development and construction of neural circuits. Additional resource: HHMI BioInteractive “Building Brains: The Molecular Logic of Neural Circuits.” Part of the lecture series “Making Your Mind: Molecules, Motion and Memory.” https://www.biointeractive.org/professional-learning/science-talks/building-brains-molecular-logic-n eural-circuits HOW DOES ONE CELL GIVE RISE TO THE ENTIRE NERVOUS SYSTEM? Neurogenesis: neurons are born Migration: neurons find their place and build e.g. cortex Differentiation: determination of cell fate Target innervation: Address selection Synapse formation: formation of connections At peak times during development 250,000 nerve cells are added per minute LEARNING OUTCOMES By the end of the three lectures, and following revision of the associated learning material, you should be able to: Describe the processes of neurogenesis, differentiation, migration Describe the process of target innervation Describe the principles of synapse formation and elimination NEUROGENESIS Formation of notochord at midline Neural plate develops from overlying ectoderm (neuroectoderm) Neuroectodermal precursor cells: neurulation This will give rise to the entire nervous system! NEUROGENESIS Neural plate folds inwards Closes: neural tube Floorplate above notochord; Where tube closes: roofplate And neural crest cells NEUROGENESIS Notochord, floorplate and roofplate are transient structures, essential for instructing nervous system formation Anterior end: brain Neural tube near somites: spinal cord Neural crest: separates from neural tube, major components of PNS Lumen of the tube: ventricles (CSF) NEUROGENESIS AND DIFFERENTIATION: HOW DO NEURONS BECOME DIFFERENT? High degree of patterning in the neural tube: Anterior/ posterior (rostral/ caudal) along the length of the tube Dorsal-ventral in cross section Patterning is instructed by morphogens NEUROGENESIS AND DIFFERENTIATION: HOW DO NEURONS BECOME DIFFERENT? Anterior-posterior patterning: Proliferation and segmentation generates the early spinal cord and 3 primary vesicles: brainstem, midbrain and forebrain..AND THIS IS WHAT IT LOOKS LIKE IN “REAL LIFE” Zebrafish early development, 8-20hpf, Huisken lab, MPI Dresden HOW DOES THIS DEVELOP INTO A BRAIN? HOW DOES THIS DEVELOP INTO A BRAIN? The size of the cortex, particularly the frontal lobe, distinguishes humans from animals the brain determines the person, it makes us who we are LEARNING OUTCOMES By the end of the three lectures, and following revision of the associated learning material, you should be able to: Describe the processes of neurogenesis, differentiation, migration Describe the process of target innervation Describe the principles of synapse formation and elimination NEUROGENESIS AND DIFFERENTIATION When and where a neuron is born determines its ultimate fate Morphogen gradients drive differentiation Wnt, BMPs FGF FGF - Fibroblast growth factors; Wnt - Wingless-related integration sites; BMP – Bone morphogenetic proteins  roofplate BMP Shh floorplate BMP – Bone morphogenetic proteins; Shh – Sonic Hedgehog HOW MORPHOGENS ACT? Morphogens bind to receptors to activate or repress sets of transcription factors Transcription factors control gene expression programs Gene expression profiles determine cell identity Distance from the secreting cells (gradients) / availability of ligand + presence of receptors determine response of each cell Hox genes: Family of transcription factors Establish segmentation along anterior- posterior axis Hox genes – Homeobox genes HOW DO WE KNOW THAT CELL FATE CAN BE INDUCED? Graft of tissue from pigmented to non-pigmented amphibian embryo Secondary axis developed, mixed origin => Transplanted cells instructed host cells! “Spemann-Mangold organiser” (1923, Nobel prize for Hans Spemann in 1935) LEARNING OUTCOMES By the end of the three lectures, and following revision of the associated learning material, you should be able to: Describe the processes of neurogenesis, differentiation, migration Describe the process of target innervation Describe the principles of synapse formation and elimination LEARNING OUTCOMES – NEXT WEEK By the end of the three lectures, and following revision of the associated learning material, you should be able to: Describe the processes of neurogenesis, differentiation, migration Describe the process of target innervation Describe the principles of synapse formation and elimination