Patterning the central nervous system

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Patterning the central nervous system

• 1. master genes
• 2. induction
• Neurogenesis,
• Fate determination during proliferation
• Fate determination during differentiation
• Gain of function and loss of function
• Markers

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The early vertebrate brain vesicles and neuromeres
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Patterning forebrain
Lateral neural tube
pituitary and mammillary region of hypothalamus
Division of telencephalon and diencephalon BF-1-/
- deletion of ventral telecephalon and severe
reduction of the cortex
Emx1 Emx2 in pallium Dlx1 Dlx2 in striatum
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1. Otx2
2. Rostral pole of neural plate, row-1, ANR (FGF8 to
   BF-1), as secondary signaling center, set up by
   prechordal endoderm

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Patterning dorsal telencephalic regions (pallium,
future cortex) Genes Pax6, Tbr1,
Emx1ltEmx2ltOtx1ltOtx2
Patterning ventral telencephalic region (LGE,
MGE, future striatum and globus pallidus), Dlx,
Nkx2.1
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Emx1 KO corpus callosum Emx2 KO hippocampal
dentate gyrus and the CR cells (reeler) Gli3 KO
Disruption of dorsal telecephalic-diencephalic
boundary cortical lamination defects. Further
specification of dorsal telencephalon incoming
thalamic afferents Ventral telencephalon Dorsalat
eral LGE to striatum Ventromedial MGE to
globus pallidus Nkx2.1 KO, more striatum Pax6
to R-cadherin, LewisX antigen, KO lose
corticostriatal boundary Transplantation
community effect (tissue vs. single cells)
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Small GABAergic inhibitory interneurons
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Diencephalic regionalization Parencephalon to
ventral (anterior) and dorsal (posterior)
thalamus, zli (zona limitans intrathalamica) VT (
Dlx1 and Dlx2), DT (Gbx2 and Wnt3) Zli (SHH,
mamillothalamic tract) Synencephalon to
anterior, posterior (pretectum) Prosomere cell
lineage restriction, virus?
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Zli transition from epichordal to prechordal
regions, SHH, Dlx in ventral thalamus, Gbx2 and
Wnt3 in dorsal thalamus. Pax6 in pretetum, vs,
En and Pax2 in mesencephalon.
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Midbrain Dorsal tectum, torus semicircularis,
(superior and inferior colliculi) Ventral
substantia nigra, ventral tegmental area, motor
neurons of oculomotor nerve.
Tectum AP polarity. Epherin (controlled by En)
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Patterning of midbrain by isthmus
Position of isthmus is decided by Otx2 and Gbx2,
(Otx2-/, Otx1-/-)
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Midbrain inversion, En expression Isthmus
transplantation Wnt1 maintenance of En FGF8
induction Pax2, 5, 8 for isthmus formation
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FGF8 is not enough to induce cerebellum in
rostral hindbrain. DV axis is dependent on SHH
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Hindbrain
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Segmentation and neuronal pattern, rhombomere,
boundary, gene expression, pairwise organization
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Repetitive reticular neurons Two-segment repeat
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Compartment
Young neurons vs. ventricular zone
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Partition by adhesion EphA4, EphB2, EphB3 in r3,
r5 (by Krox20, by Kreisler (r5, r6)) EphrinB in
r2, r4, r6
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Retinoids on Hox Birth defects in hindbrain Hox
expression change RARE Raldh2, in presomitic
mesoderm, source Cyp26, inactivates RA in
midbrain and forebrain, sink. FGF8 as an
anterior inhibitor of Hox and induces cerebellum
in r1.
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Spinal cord and somites
Relay model Gradient model
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Pax genes encode DV value?
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Target genes of SHH HNF3b, Nkx2.1, Nkx2.2, Isl1,
Pax3, Pax6, Msx1
Sequential induction, RA specification
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LMCM Isl1, Isl2 LMCL Isl2, Lim1 MMCL Isl1,
Isl2 MMCM Isl1, Isl2, Lim3, Gsh4 Preganglionic
MC Isl1
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Dorsal spinal cord Slug (neural crest), Lmx1
(roof plate), LH2 (dorsal interneurons)
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Role of SHH in ventral forebrain High MGE Low
LGE
SHH as a permissive ventral inducer.
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Coordination of AP and DV patterning mechanisms
AP identity is formed earlier than DV identity