Brain Development
95
Fig. 4
Shh dependent D–V patterning
in the neural tube. (a) Various cell types
are generated along the D–V axis of the
neural tube. The floor plate cells (FP)
and the underlying axial mesoderm,
notochord cells (N) produce the
secreted molecule sonic hedgehog
(Shh)
.MN
,motorneurons
;p,
progenitor domains; RP, roof plate,
(b) Ventral sources of Shh (FP and
N) set a Shh gradient, inducing and/or
repressing distinct sets of transcription
factors within the progenitor domains.
This helps generate various types of
neurons de±ned by the functions and
gene expression pro±les. (c) The
hedgehog signaling machinery revealed
in
Drosophila
. In vertebrates, there are
three hedgehogs (Sonic, Indian, and
Desert), and Gli transcription factors are
the vertebrate homologs of Ci (
cubitus
interruptus
).
RP
Commissural
neurons
pD
Association
neurons etc.
p0
p1
p2
p3
pMN
pOC
Oligodendrocytes
Lhx3
Chx10
V2
V1
V3
V0
Sim1
Evx1
Ist1
En1
Dorsal
Ventral
N
FP
(a)
pD
p0
p1
p2
p3
pMN
from FP&N
Nkx2.2/2.9
Nkx6.1
Nkx6.2
Pax6
Pax7
Irx3
Dbx2
Dbx1
Repressed by Shh
Induced by Shh
Olig2
Shh
(b)
Hedgehog
Hedgehog
+
Patched
Patched
Smoothened
Smoothened
Costal
Suppressor of fused
Fused kinase
Cubitus interruptus (Ci)
Microtubule
Microtubule
Cleaved Ci
Large ci
Corepressor
Coactivator
(c)
MN
induce each cell type in the spinal cord.
This raises the question of how a single
molecular gradient can serve to deFne dis-
tinct progenitor domains along the D–V
axis. The known Shh receptor components
are the seven-transmembrane proteins,
Patched and Smoothened, and interac-
tions between the ligand Shh and the
receptor molecules are shown to Fnally
activate the Gli transcription factors in ver-
tebrates (refer ±ig. 4c). As the degree of
receptor activation appears to control the
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