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 Synapse: connection Between two neurons “Connections” 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 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 Patterning (organization) and morphogenesis (shape and size) Patterning and morphogenesis the neural of theofneural tubetube 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 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://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 Neuronal migration (move from birthplace to workplace) Radial route Neuronal migration http://www.brainfacts.org/~/media/Brainfacts/Article%20Multimedia/Brain%20Basics/Neuroanatomy/Neuron%20Migration.ashx Tangential route http://upload.wikimedia.org/wikipedia/commons/7/70/Interneuronradial_glial_interactions_in_the_developing_cerebral_cortex.png Axon guidance Primary (connecting with the right partner) neurulation 1. Formation of the neural plate 2. Shaping of the neural plate 3. Bending of the neural plate to form the groove 4. 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.ibdm.univ-mrs.fr/equipe/axonguidance-in-the-mammalian-brain/ http://www.neuralimages.org/images/growth-cone.gif Model system http://csatimes.co.in/wp-content/uploads/2014/02/baby-chick-and-an-egg.jpg Morphogenesis (shape and size) of Neural tube formation in the theforebrain chick embryo Patterning and morphogenesis of the neural Hippocampus tube M L D ChP V X Holoprocencephalic forebrain Blocking RA signaling in midline Axon guidance in the visual pathway The visual pathway in chicken Visual centers In the forebrain Thalamic nuclei Optic tectum Retina 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 Ventral Retina Medial Lateral Optic Tectum Roger Sperry’s chemoaffinity hypothesis Topographic guidance cues along the AP and DV axes EphA Ephrin-A temporal Caudal nasal Rostral Optic Tectum Retina Dorsal Medial Ephrin-B Ventral EphB Lateral Hypothesis Strategy to identify new retino-tectal guidance molecules : Dorsal There are as yet unidentified guidance molecules that regulate retinotectal mapformation. Ventral Total RNA Total RNA Cy5 Cy3 Microarray 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 V Lactotransferrin D V Utrophin Genes expressed at higher levels in the dorsal tectum In-vivo experiments to validate the candidate guidance molecules RNAi-mediated knockdown and misexpression of candidate retinotectal guidance molecules T A T N P DiI Injection site Termination zone in tectum Summary Regulatory molecules ? Axon guidance Neurogenesis Patterning Migration Thank you!