Brain Development And Construction Of Neural Circuits - II PDF

BIOL2051-52 BRAIN DEVELOPMENT AND CONSTRUCTION OF NEURAL CIRCUITS - II Kif Liakath-Ali, PhD [email protected] www.splicelab.co.uk LEARNING OUTCOMES – LAST WEEK By the end of the three lectures, and following revision of...

BIOL2051-52 BRAIN DEVELOPMENT AND CONSTRUCTION OF NEURAL CIRCUITS - II Kif Liakath-Ali, PhD [email protected] www.splicelab.co.uk LEARNING OUTCOMES – LAST 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 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) 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 WHAT HAPPENS IF GRADIENTS GO WRONG? One example: lack of Shh Optic vesicles generated on dorsal side Shh inhibition/loss leads to loss of ventral identity => Synophthalmia (“cyclopia”) LEARNING OUTCOMES - TODAY 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 DO NEURONS GET INTO THEIR CORRECT PLACE? EXAMPLE: BUILDING THE CORTEX DIFFERENTIATION AND MIGRATION: BUILDING THE CORTEX Neuroepithelium/Neuroepithelial progenitor cells in neural tube = neural precursor cells Form the ventricular zone Radial glia connect the ventricular and pial surface, divide slowly and symmetrically Precursors divide asymetrically in the ventricular zone (innermost layer of neural tube) (“transit amplifying cells”) Generate new progenitors and postmitotic neuroblasts MIGRATION Neuroblast migrate to pial surface Form the marginal zone Differentiate into neurons Newer neuroblasts migrate past their older cousins => Cortex is built “inside out” A neuron’s final location reveals its birthdate => Columnar organisation NOT JUST NEURONS: ORIGIN OF GLIA Also generated from neuroepithelium Over time, glioblasts either remain attached to lumen and become ependymal cells (production of CSF) Or they move to the marginal layer and form astrocytes (maintenance and repair) or oligodendrocytes (myelination) MIGRATION IN ACTION Guerrier et al, Cell 2009 Hill, M.A. (2014) Embryology Stage 22 image 217.jpg. Retrieved September 28, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=File:Stage_22_image_217.j pg Ramon y Cajal CORTICAL INTERNEURONS HAVE A DIFFERENT ORIGIN! Interneurons are born in the ganglionic eminences Migrate tangentially Nery et al., Nat Neurosci 2002 EARLY DEVELOPMENT- SUMMARY https://learninglink.oup.com/access/content/purves6xe-student-resources/animation-22-1?previousFilter=tag_animatio ns Now that neurons are specified and in their correct place, how to form a network? LEARNING OUTCOMES - TODAY 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 POLARISATION “neurites” grow out Axon and dendrites are established Cell body and dendrites axons Dotti et al, 1988 TARGET INNERVATION To be functional, brains need to be wired correctly Many different neurons extend axons – random mix of spaghetti fibers? NO! Highly ordered structure Function of the brain depends on ordered circuits TARGET INNERVATION How does a growing process navigate through the embryonic body? Does the process know the entire route as it sets out? Growing processes use cues/ signals to help them navigate from “stepping stone” to “stepping stone”… They also “piggy back” along the way! “fasciculation” LEARNING OUTCOMES - TODAY 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 DO AXONS FIND THEIR CORRECT TARGET? LEARNING OUTCOMES – NEXT TIME 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