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Exploring how the brain is shaped and wired

Exploring how the brain is shaped and wired. http://www.greenspine.ca/media/neuron_culture_800px.jpg. Jonaki Sen BSBE Department, IIT Kanpur. http://www.cs4fn.org/biology/images/brainxray.jpg. Input received through dendrite. Cell body of neuron containing DNA. Output sent through axon.

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Exploring how the brain is shaped and wired

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  1. Exploring how the brain is shaped and wired http://www.greenspine.ca/media/neuron_culture_800px.jpg Jonaki Sen BSBE Department, IIT Kanpur http://www.cs4fn.org/biology/images/brainxray.jpg

  2. Input received through dendrite Cell body of neuron containing DNA Output sent through axon Synapse: connection Between two neurons

  3. “Connections”

  4. Embryonic development Neural development http://www.greenspine.ca/media/neuron_culture_800px.jpg ? ? http://www.pieuvre.ca/2013/05/04/science-cellules-division/zygote/ http://www.hdwallpapers-3d.com/human-body-pictures/ http://www.cs4fn.org/biology/images/brainxray.jpg

  5. Series of events that build the brain • Patterning and morphogenesis of the neural tube • Neurogenesis: production of neurons • Neuronal differentiation • Neuronal migration • Axon guidance and synaptogenesis

  6. Patterning(organization) and morphogenesis (shape and size) of the neural tube Patterning and morphogenesis of the neural tube http://www.ib.cnea.gov.ar/~redneu/2013/BOOKS/Principles%20of%20Neural%20Science%20-%20Kandel/gateway.ut.ovid.com/gw2/ovidweb.cgisidnjhkoalgmeho00dbookimagebookdb_7c_2fc~61.htm http://www.mun.ca/biology/desmid/brian/BIOL3530/DEVO_05/ch05f32.jpg http://www.mun.ca/biology/desmid/brian/BIOL3530/DEVO_05/ch05f32.jpg

  7. Neurogenesis (production of neurons) and Neuronal differentiation (acquiring the properties of a neuron) Neurogenesis: production of neurons http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00064/full http://www.ibmb.csic.es/index.php?pg=laboratorio&tab=186&idLaboratorio=18 http://mindsparke.com/brain-training-blog/wp-content/uploads/2010/03/neurogenesis.jpg http://www.ibmb.csic.es/index.php?pg=laboratorio&tab=186&idLaboratorio=18

  8. Neuronal migration (move from birthplace to workplace) Radial route Tangential route Neuronal migration http://upload.wikimedia.org/wikipedia/commons/7/70/Interneuron-radial_glial_interactions_in_the_developing_cerebral_cortex.png http://www.brainfacts.org/~/media/Brainfacts/Article%20Multimedia/Brain%20Basics/Neuroanatomy/Neuron%20Migration.ashx

  9. Axon guidance (connecting with the right partner) Primary neurulation • Formation of the neural plate • Shaping of the neural plate • Bending of the neural plate to form the groove • Closure of the neural groove to form the neural tube. http://www.mun.ca/biology/desmid/brian/BIOL3530/DEVO_12/ch12f19.jpg http://briebuzz.blogspot.in/ http://www.neuralimages.org/images/growth-cone.gif http://www.ibdm.univ-mrs.fr/equipe/axon-guidance-in-the-mammalian-brain/ http://www.mun.ca/biology/desmid/brian/BIOL3530/DEVO_12/ch12f19.jpg

  10. Model system http://csatimes.co.in/wp-content/uploads/2014/02/baby-chick-and-an-egg.jpg

  11. Morphogenesis (shape and size) of the forebrain Neural tube formation in the chick embryo

  12. Patterning and morphogenesis of the neural tube Hippocampus M L D ChP X V Holoprocencephalic forebrain

  13. Blocking RA signaling in midline

  14. Axon guidance in the visual pathway

  15. The visual pathway in chicken Visual centers In the forebrain Thalamic nuclei Optic tectum Retina

  16. Ganglion cells from specific locations in the chick retina project to specific locations in the optic tectum. This gives rise to the retinotectal map Dorsal Medial Lateral Ventral Retina Optic Tectum

  17. Roger Sperry’s chemoaffinity hypothesis

  18. Topographic guidance cues along the AP and DV axes EphA Ephrin-A Caudal temporal nasal Rostral Optic Tectum Retina Dorsal Ephrin-B Medial Ventral Lateral EphB

  19. Strategy to identify new retino-tectal guidance molecules : Hypothesis Dorsal There are as yet unidentified guidance molecules that regulate retinotectal map-formation. Ventral Cy5 Total RNA Total RNA Cy3 Microarray

  20. Candidate topographic guidance molecules expressed asymmetrically along the dorsal-ventral axis of the tectum D D D V V V Ten-M3 homolog Coiled coil domain containing 46 Wnt-5A D D V V Lactotransferrin Utrophin Genes expressed at higher levels in the dorsal tectum

  21. In-vivo experiments to validate the candidate guidance molecules T T N DiI Injection site A A P P WT RNAi-mediated knockdown and misexpression of candidate retinotectal guidance molecules Termination zone in tectum

  22. Summary Regulatory molecules ? Axon guidance Neurogenesis Patterning Migration

  23. Thank you!

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