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) 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

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 http://www.ibmb.csic.es/index.php?pg=laboratorio&tab=186&idLaboratorio=18

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

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

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

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

Holoprocencephalic forebrain Patterning and morphogenesis of the neural tube D V M L Hippocampus ChP 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 This is a cartoon of the visual pathways in the chicken, which is the avian model organism we study. We chose the chicken primarily because of the larger size of the various components of the visual pathway as compared to the mouse. As you can see in this cartoon there are two visual pathways carrying visual information from the retina. The lemnothalamic pathway (dashed line) goes from the retina to the OPT in the thalamus and then to the visual Wulst. The Collothalamic one (solid line) goes from the retina to the optic tectum in the mid-brain, from there to the nucleus rotundus in the thalamus and thereafter to the Ectostriatum in the telencephalon. This second one is the major pathway in the birds. Optic tectum Retina

rise to the retinotectal map 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

Roger Sperry’s chemoaffinity hypothesis

Retina Ephrin-A Ephrin-B 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

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

Candidate topographic guidance molecules expressed asymmetrically along the dorsal-ventral axis of the tectum D D D V V V Coiled coil domain containing 46 Ten-M3 homolog Wnt-5A D D V V Lactotransferrin 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 N A P WT DiI Injection site Termination zone in tectum

Summary ? Patterning Neurogenesis Axon guidance Migration Regulatory molecules ? Neurogenesis Axon guidance Patterning Migration

Thank you!