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!