The molecular bases of brain development and CNS malignancies remain poorly understood. Here we show that Sonic hedgehog (Shh) signaling controls the development of the cerebellum at multiple levels. SHH is produced by Purkinje neurons, it is required for the proliferation of granule neuron precursors and it induces the differentiation of Bergmann glia. Blocking SHH function in vivo results in deficient granule neuron and Bergmann glia differentiation as well as in abnormal Purkinje neuron development. Thus, our findings provide a molecular model for the growth and patterning of the cerebellum by SHH through the coordination of the development of cortical cerebellar cell types. In addition, they provide a cellular context for medulloblastomas, childhood cancers of the cerebellum.

Reference

Alder
J.
,
Cho
N. K.
,
Hatten
M. E.
(
1996
)
Embryonic precursor cells from the rhombic lip are specified to a cerebellar granule neuron identity.
Neuron
17
,
389
399
Ang
S. L.
,
Rossant
J.
(
1994
)
HNF-3is essential for node and notochord formation in mouse development.
Cell
78
,
561
574
Aruga
J.
,
Yokota
N.
,
Hashimoto
M.
,
Furuichi
T.
,
Fukuda
M.
,
Mikoshiba
K. A.
(
1994
)
Novel zinc finger protein, Zic, is involved in neurogenesis, especially in the cell lineage of cerebellar granule cells.
J. Neurochem
63
,
1880
1890
Aruga
J.
,
Nagai
T.
,
Tokuyama
T.
,
Hayashizaki
Y.
,
Okazaki
Y.
,
Chapman
V. M.
,
Mikoshiba
K.
(
1996
)
The mouse Zic gene family: homologues of Drosophila pair-rule gene odd-paired.
J. Biol. Chem
271
,
1043
1047
Baptista
C. A.
,
Hatten
M. E.
,
Blazeski
R.
,
Mason
C. A.
(
1994
)
Cell-cell interactions influence survival and differentiation of purified Purkinje cells in vitro.
Neuron
12
,
243
260
Belloni
E.
,
Muenke
M.
,
Roessler
E.
,
Traverso
G.
,
Siegel-Bartelt
J.
,
Frumkin
A.
,
Mitchell
H. F.
,
Donis-Keller
H.
,
Helms
C.
,
Hing
A. V.
,
Heng
H. H. Q.
,
Koop
B.
,
Martindale
D.
,
Rommens
J. M.
,
Tsui
L.-C.
,
Scherer
S. W.
(
1996
)
Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly.
Nature Genetics
14
,
353
356
Ben-Arie
N.
,
Bellen
H. J.
,
Armstrong
D. L.
,
McCall
A. E.
,
Gordadze
P. R.
,
Guo
Q.
,
Matzuk
M. M.
,
Zoghbi
H. Y.
(
1997
)
Math1 is essential for genesis of the cerebellar granule neurons.
Nature
390
,
169
172
Chiang
C.
,
Litingtung
Y.
,
Lee
E.
,
Young
K. E.
,
Corden
J. L.
,
Westphal
H.
,
Beachy
P. A.
(
1996
)
Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function.
Nature
383
,
407
413
Cooper
M. K.
,
Porter
J. A.
,
Young
K. E.
,
Beachy
P. A.
(
1998
)
Teratogen-mediated inhibition of target tissue response to Shh signaling.
Science
280
,
1603
1607
Curran
T.
,
D'Arcangelo
G.
(
1998
)
Role of Reelin in the control of brain development.
Brain Research
26
,
285
294
Dahmane
N.
,
Lee
J.
,
Robins
P.
,
Heller
P.
,
Ruiz i Altaba
A.
(
1997
)
Activation of the transcription factor Gli1 and the Sonic hedgehog signaling pathway in skin tumors.
Nature
389
,
876
881
D'Ercole
J. A.
,
Ye
P.
,
Calikoglu
A. S.
,
Gutierrez-Ospina
G.
(
1996
)
The role of Insulin-like growth factors in the central nervous system.
Mol. Neurobiol
13
,
227
255
Dehart
D. B.
,
Lanoue
L.
,
Tint
G. S.
,
Sulik
K. K.
(
1997
)
Pathogenesis of malformations in a rodent model for Smith-Lemli-Opitz Syndrome.
Amer. J. Med. Genet
68
,
328
337
Duprez
D.
,
Fournier-Thibault
C.
,
Le Douarin
N.
(
1998
)
Sonic hedgehog induces proliferation of committed skeletal muscle cells in the chick limb.
Development
125
,
495
505
Dusart
I.
,
Airaksinen
M. S.
,
Sotelo
C.
(
1997
)
Purkinje cell survival and axonal regeneration are age dependent: an In vitro study.
J. Neurosci
17
,
3710
3726
Echelard
Y.
,
Epstein
D. J.
,
St-Jacques
B.
,
Shen
L.
,
Mohler
J.
,
McMahon
J. A.
,
McMahon
A. P.
(
1993
)
Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity.
Cell
75
,
1417
1430
Ericson
J.
,
Mortin
S.
,
Kawakami
A.
,
Roelink
H.
,
Jessell
T. M.
(
1996
)
Two critical periods of sonic hedgehog signaling required for the specification of motor neuron identity.
Cell
87
,
661
673
Ericson
J.
,
Rashbass
P.
,
Schedl
A.
,
Brenner-Morton
S.
,
Kawakami
A.
,
van Heyningen
V.
,
Jessell
T. M.
,
Briscoe
J.
(
1997
)
Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling.
Cell
90
,
169
180
Fan
C.-M.
,
Porter
J. A.
,
Chiang
C.
,
Chang
D. T.
,
Beachy
P. A.
,
Tessier-Lavigne
M.
(
1995
)
Long-range sclerotome induction by Sonic hedgehog direct role of the amino terminal cleavage product and modulation by the cyclic AMP signaling pathway.
Cell
81
,
457
465
Farese
R. V. J.
,
Herz
J.
(
1998
)
Cholesterol metabolism and embryogenesis.
Trends Genet
14
,
115
120
Feng
L.
,
Hatten
M. E.
,
Heintz
N.
(
1994
)
Brain lipid-binding protein (BLBP): a novel signaling system in the developing mammalian CNS.
Neuron
12
,
895
908
Fischer
M.
,
Trimmer
P.
,
Ruthel
G.
(
1993
)
Bergmann glia require continuous association with Purkinje cells for normal phenotype expression.
Glia
8
,
172
182
Fruttiger
M.
,
Calver
A. R.
,
Kruger
W. H.
,
Mudhar
H. S.
,
Michalovich
D.
,
Takakura
N.
,
Nishikawa
S.
,
Richardson
W. D.
(
1996
)
PDGF mediates a neuron-astrocyte interaction in the developing retina.
Neuron
17
,
1117
1131
Fruttiger
M.
,
Karlsson
L.
,
Hall
A. C.
,
Abramsson
A.
,
Calver
A. R.
,
Boström
H.
,
Willetts
K.
,
Bertold
C.-H.
,
Heath
J. K.
,
Betsholtz
C.
,
Richardson
W. D.
(
1999
)
Defective oligodendrocyte development andsevere hypomyelination in PDGF-A knockout mice.
Development
126
,
457
467
Furley
A. J.
,
Morton
S. B.
,
Manalo
D.
,
Karagogeos
D.
,
Dodd
J.
,
Jessell
T. M.
(
1990
)
The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity.
Cell
61
,
157
170
Gailani
M. R.
,
Stahle-Backdahl
M.
,
Leffell
D. J.
,
Glynn M. Zaphiropoulos
P. G.
,
Pressman
C.
,
Unden
A. B.
,
Dean
M.
,
Brash
D. E.
,
Bale
A. E.
,
Toftgard
R.
(
1991
)
The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas.
Nature Genet
14
,
7
8
Gao
W.-Q.
,
Heintz
N.
,
Hatten
M. E.
(
1991
)
Cerebellar granule cell neurogenesis is regulated by cell-cell interactions in vitro.
Neuron
6
,
705
715
Goldowitz
D.
,
Cushing
R. C.
,
Laywell
E.
,
D'Arcangelo
G.
,
Shelon
M.
,
Sweet
H.O.
,
Davisson
M.
,
Steindler
D.
,
Curran
T.
(
1997
)
Cerebellar disorganization characteristic of reeler in scrambler mutant mice despite presence of reelin.
J. Neurosci
17
,
8767
8777
Goodrich
L. V.
,
Johnson
R. L.
,
Milenkovic
L.
,
McMahon
J. A.
,
Scott
M. P.
(
1996
)
Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog.
Genes Dev
10
,
301
312
Goodrich
L. V.
,
Milenkovic
L.
,
Higgins
K. M.
,
Scott
M. P.
(
1997
)
Altered neural cell fates and medulloblastoma in mouse patched mutants.
Science
277
,
1109
1113
Hahn
H.
,
Wicking
C.
,
Zaphiropoulos
P. G.
,
Gailani
M. R.
,
Shanley
S.
,
Chidambaram
A.
,
Vorechovsky
I.
,
Holmberg
E.
,
Unden
A. B.
,
Gillies
S.
,
Negus
K.
,
Smyth
I.
,
Pressman
C.
,
Leffell
D. J.
,
Gerrard
B.
,
Goldstein
A. M.
,
Dean
M.
,
Toftgard
R.
,
Chenevix-Trench
G.
,
Wainwright
B.
,
Bale
A. E.
(
1996
)
Mutations ofthe human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome.
Cell
85
,
841
851
Hatten
M. E.
(
1985
)
Neuronal regulation of astroglial morphology and proliferation in vitro.
J. Cell Biol
100
,
384
396
Hatten
M. E.
,
Heintz
N.
(
1995
)
Mechanisms of neural patterning and specification in the developing cerebellum.
Annu Rev. Neurosci
18
,
385
408
Hatten
M. E.
,
Alder
J.
,
Zimmerman
K.
,
Heintz
N.
(
1997
)
Genes involved in cerebellar cell specification and differentiation.
Current Opin. Neurobiol
7
,
40
47
Herrup
K.
,
Kuemerle
B.
(
1997
)
The compartmentalization of the cerebellum.
Annu. Rev.Neurosci
20
,
61
90
Howell
B. W.
,
Hawkes
R.
,
Soriano
P.
,
Cooper
J. A.
(
1997
)
Neuronal position in the developing brain is regulated by mouse disabled-1.
Nature
389
,
733
–.
Huang
Z.
,
Kunes
S.
(
1996
)
Hedgehog, transmitted along retinal axons, triggers neurogenesis in the developing visual centers of the Drosophila brain.
Cell
86
,
411
422
Incardona
J. P.
,
Gaffield
W.
,
Kapur
R. P.
,
Roelink
H.
(
1998
)
The teratogenic veratrum alkaloid cyclopamine inhibits Sonic Hedgehog signal transduction.
Development
125
,
3553
3562
Jankovski
A.
,
Rossi
F.
,
Sotelo
C.
(
1996
)
Neuronal precursors in the postnatal mouse cerebellum are fully committed cells: evidence from heterochronic transplantations.
Eur. J. Neurosci
8
,
2308
2319
Jensen
A. M.
,
Wallace
V. A.
(
1997
)
Expression of Sonic hedgehog and its putative role as a precursor cell mitogen in the developing mouse retina.
Development
124
,
363
371
Johnson
R. L.
,
Rothman
A. L.
,
Xie
J.
,
Goodrich
L. V.
,
Bare
J. W.
,
Bonifas
J. M.
,
Quinn
A. G.
,
Myers
R. M.
,
Cox
D. R.
,
Epstein
E. H.
Jr.
,
Scott
M. P.
(
1996
)
Human homolog of Patched, a candidate gene for basal cell nevus syndrome.
Science
272
,
1668
1671
Kelly
R. I.
,
Roessler
E.
,
Hennekkam
R. C. M.
,
Feldman
G. L.
,
Kosaki
K.
,
Jones
M. C.
,
Palumbos
J. C.
,
Muenke
M.
(
1996
)
Holoprosencephaly in RSH/Smit-Lemli-Opitz Syndrome: Does abnormal cholesterol metabolism affect the function of sonic hedgehog?.
Am. J. Med. Genet
66
,
478
484
Kozmik
Z.
,
Sure
U.
,
Ruedi
D.
,
Busslinger
M.
,
Aguzzi
A.
(
1995
)
Deregulated expression of PAX5 in medulloblastoma.
Proc. Natl. Acad. Sci. USA
92
,
5709
5713
Krauss
S.
,
Concordet
J.-P.
,
Ingham
P. W.
(
1993
)
A functionally conserved homolog of the Drosophila segment polarity gene hedgehog is expressed in tissues with polarizing activity in zebrafish embryos.
Cell
75
,
1431
1444
Kuhar
S. G.
,
Feng
L.
,
Vidan
S.
,
Ross
M. E.
,
Hatten
M. E.
,
Heintz
N.
(
1993
)
Changing patterns of gene expression define four stages of cerebellar granule neuron differentiation.
Development
117
,
97
104
Lanoue
L.
,
Dehart
D. B.
,
Hinsdale
M. E.
,
Maeda
N.
,
Tint
G. S.
,
Sulik
K. K.
(
1997
)
Limb, genital, CNS, and facial malformations result from gene/environment-induced cholesterol deficiency: further evidence for a link to Sonic hedgehog.
Am.J. Med. Genet
73
,
24
31
Lee
J.
,
Platt
K.
,
Censullo
P.
,
Ruiz i Altaba
A.
(
1997
)
Gli1 is a target of Sonic hedgehog that induces ventral neural tube development.
Development
124
,
2537
2552
Lin
J. C.
,
Cepko
C. L.
(
1998
)
Granule cell raphes and parasagittal domains of Purkinje cells: complementary patterns in the developing chick cerebellum.
J. Neurosci
18
,
9342
9353
Marigo
V.
,
Johnson
R. L.
,
Vortkamp
A.
,
Tabin
C. J.
(
1996
)
Sonic hedgehog differentially regulates expression of Gli and Gli3 during limb development.
Dev. Biol
180
,
273
283
Miao
N.
,
Wang
M.
,
Ott
J. A.
,
D'Alessandro
J. S.
,
Woolf
T. M.
,
Bumcrot
D. A.
,
Mahanthappa
N. K.
,
Pang
K.
(
1997
)
Sonic Hedgehog promotes the survival of specific CNS neuron populations and protects these cells form toxic insult in vitro.
J. Neurosci
17
,
5891
5899
Millen
K. J.
,
Hui
C.-C.
,
Joyner
A. L.
(
1995
)
A role for En-2 and other murine homologues of Drosophila segment polarity genes in regulating positional information in the developing cerebellum.
Development
121
,
3935
3945
Miyata
T.
,
Nakajima
K.
,
Mikoshiba
K.
,
Ogawa
M.
(
1997
)
Regulation of Purkinje cell alignment by reelin as revealed with CR-50 antibody.
J. Neurosci
17
,
3599
3609
Ness
G. C.
,
Lopez
D.
,
Borrego
O.
,
Gilbert-Barness
E.
(
1997
)
Increased expression of low-density lipoprotein receptors in a Smith-Lemli-Opitz infant with elevated bilirubin levels.
Am. J. Med. Genet
68
,
294
299
Nothias
F.
,
Fishell
G.
,
Ruiz i Altaba
A.
(
1998
)
Cooperation of intrinsic and extrinsic signals in the elaboration of regional identity in the posterior cerebral cortex.
Curr.Biol
8
,
459
462
Oro
A. E.
,
Higgins
K. M.
,
Hu
Z.
,
Bonifas
J. M.
,
Epstein
E. H.
Jr.
,
Scott
M. P.
(
1997
)
Basal cell carcinomas in mice overexpressing Sonic hedgehog.
Science
276
,
817
821
Poncet
C.
,
Soula
C.
,
Trousse
F.
,
Kan
P.
,
Hirsinger
E.
,
Pourquie
O.
,
Duprat
A.-M.
,
Cochard
P.
(
1996
)
Induction of oligodendrocyte progenitors in the trunk neural tube by ventralizing signals: effects of notochord and floor plate grafts, and of sonic hedgehog.
Mech. Dev
60
,
13
32
Porter
J. A.
,
Young
K. E.
,
Beachy
P. A.
(
1996
)
Cholesterol modification of hedgehog signaling proteins in animal development.
Science
274
,
255
269
Pringle
N. P.
,
Yu
W.-P.
,
Guthrie
S.
,
Roelink
H.
,
Lumsden
A.
,
Peterson
A. C.
,
Richardson
W. D.
(
1996
)
Determination of neuroepithelial cell fate: induction of the oligodendrocyte lineage by ventral midline cells and Sonic hedgehog.
Dev. Biol
177
,
30
42
Reifenberger
J.
,
Wolter
M.
,
Weber
R. G.
,
Mgahed
M.
,
Ruzicka
T.
,
Lichter
P.
,
Reifenberger
G.
(
1998
)
Missense mutations in SMOH in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system.
Cancer Res
58
,
1798
1803
Repetto
M.
,
Maziere
J. C.
,
Citadelle
D.
,
Dupus
R.
,
Meier
M.
,
Biade
S.
,
Quiec
D.
,
Roux
C.
(
1990
)
Teratogenic effect of the cholesterol synthesis inhibitor AY 9944 on rat embryos in vitro.
Teratology
42
,
611
618
Rio
C.
,
Rieff
H. I.
,
Qi
P.
,
Corfas
G.
(
1997
)
Neuregulin and erbB receptors play a critical role in neuronal migration.
Neuron
19
,
39
50
Roelink
H.
,
Augsburger
A.
,
Heemskerk
J.
,
Korzh
V.
,
Norlin
S.
,
Ruiz i Altaba
A.
,
Tanabe
Y.
,
Placzek
M.
,
Edlund
T.
,
Jessell
T. M.
,
Dodd
J.
(
1994
)
Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord.
Cell
76
,
761
775
Roessler
E.
,
Belloni
E.
,
Gaudenz
K.
,
Jay
P.
,
Berta
P.
,
Scherer
S. W.
,
Tsui
L.-C.
,
Muenke
M.
(
1996
)
Mutations in the human Sonic Hedgehog gene cause holoprosencephaly.
Nature Genetics
14
,
357
360
Ruiz i Altaba
A.
(
1994
)
Coexpression of HNF-3and Isl-1/2 and mixed distribution of ventral cell types in the early neural tube.
Int. J. Dev. Biol
40
,
1081
1088
Ruiz i Altaba
A.
(
1997
)
Catching a Gli-mpse of hedgehog.
Cell
90
,
193
196
Ruiz i Altaba
A.
(
1998
)
Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog.
Development
125
,
2203
2212
Ruiz i Altaba
A.
,
Jessell
T. M.
,
Roelink
H.
(
1995
)
Restrictions to Floor Plate Induction by hedgehog and Winged Helix Genes in the Neural Tube of Frog Embryos.
Mol. Cell. Neurosci
6
,
106
121
Salen
G.
,
Shefer
S.
,
Batta
A. K.
,
Tint
G. S.
,
Xu
G.
,
Honda
A.
,
Irons
M.
,
Elias
E. R.
(
1996
)
Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome.
J. Lipid Res
37
,
1169
1180
Sasaki
H.
,
Hui
C. C.
,
Nakafuku
M.
,
Kondoh
H.
(
1997
)
A binding site for Gli proteins is essential for HNF-3floor plate enhancer activity in transgenics and can respond to Shh in vitro.
Development
124
,
1313
1322
Smeyne
R. J.
,
Chu
T.
,
Lewin
A.
,
Bian
F. S.
,
-Crisman
S.
,
Kunsch
C.
,
Lira
S. A.
,
Oberdick
J.
(
1995
)
Local control of granule cell generation by cerebellar Purkinje cells.
Molec. Cell. Neurosci
6
,
230
251
Sockanathan
S.
,
Jessell
T. M.
(
1998
)
Motor neuron-derived retinoid signalng specifies the subtype identity of spinal motor neurons.
Cell
94
,
503
514
Sotelo
C.
,
Alvarado-Mallart
R.-M.
,
Frain
M.
,
Vernet
M.
(
1994
)
Molecular plasticity of adult Bergmann fibers is associated with radial migration of grafted Purkinje cells.
J. Neurosci
14
,
124
133
St.-Jacques
B.
,
Dassule
H. R.
,
Karavanova
I.
,
Botchkarev
V. A.
,
Li
J.
,
Danielian
P. S.
,
McMahon
J. A.
,
Lewis
P. M.
,
Paus
R.
,
McMahon
A. P.
(
1998
)
Sonic hedgehog signaling is essential for hair development.
Curr. Biol
8
,
1058
1068
Sun
T.
,
Pringle
N. P.
,
Hardy
A. P.
,
Richardson
W. D.
,
Smith
H. K.
(
1998
)
Pax6 influences the time and site of origin of glial precursors in the central neural tube.
Mol. Cell. Neurosci
12
,
228
239
Tessier-Lavigne
M.
,
Placzek
M.
,
Lumsden
A. G.
,
Dodd
J.
,
Jessell
T. M.
(
1988
)
Chemotropic guidance of developing axons in the mammalian central nervous system.
Nature
336
,
775
778
Traiffort
E.
,
Charytoniuk
D. A.
,
Faure
H.
,
Ruat
M.
(
1998
)
Regional distribution of Sonic Hedgehog, Patched, and Smoothened mRNA in the adult rat brain.
J. Neurochem
70
,
1327
1330
Trojanowski
J. Q.
,
Tohyama
T.
,
Lee
V. M.-Y.
(
1992
)
Medulloblastomas and related primitive neuroectodermal brain tumors of childhood recapitulate molecular milestones in the maturation of neuroblasts.
Mol. Chem. Neuropath
17
,
121
135
Weinstein
D. C.
,
Ruiz i Altaba
A.
,
Chen
W. S.
,
Hoodless
P.
,
Prezioso
V. R.
,
Jessell
T. M.
,
Darnell
J. E.
Jr
(
1994
)
The winged helix transcription factor HNF-3is required for notochord development in the mouse embryo.
Cell
78
,
575
588
Wechsler-Reya
R. J.
,
Scott
M. P.
(
1999
)
Control of neuronal precursors proliferation in the cerebellum by Sonic hedgehog.
Neuron
22
,
103
114
Xie
J.
,
Murone
M.
,
Luoh
S. M.
,
Ryan
A.
,
Gu
Q.
,
Zhang
C.
,
Bonifas
J. M.
,
Lam
C. W.
,
Hynes
M.
,
Goddard
A.
,
Rosenthal
A.
,
Epstein
E. H.
Jr.
,
de Sauvage
F. J.
(
1998
)
Activating Smoothened mutations in sporadic basal-cell carcinoma.
Nature
391
,
90
92
Yang
X. W.
,
Zhong
R.
,
Heintz
N.
(
1996
)
Granule cell specification in the developing mouse brain as defined by expression of the zinc finger transcription factor RU49.
Development
122
,
555
566
Ye
W.
,
Shimamura
K.
,
Rubenstein
J. L. R.
,
Hynes
M. A.
,
Rosenthal
A.
(
1998
)
FGF and Shh signals control Dopaminergic and Serotonergic cell fate in the anterior neural plate.
Cell
93
,
755
766
Yokota
N.
,
Aruga
J.
,
Takai
S.
,
Yamada
K.
,
Hamazaki
M.
,
Iwase
T.
,
Sugimura
H.
,
Mikoshiba
K.
(
1996
)
Predominant expression of human Zic in cerebellar granule cell lineage and medulloblastoma.
Cancer Res
56
,
377
383
Yoneshima
H.
,
Nagata
E.
,
Matsumoto
M.
,
Yamada
M.
,
Nakajima
K.
,
Miyata
T.
,
Ogawa
M.
,
Mikoshiba
K.
(
1997
)
A novel neurological mutant mice, yotari, which exhibits reeler-like phenotype but expresses CR-50 antigen/Reelin.
Neurosci. Res
29
,
217
223
Yuasa
S.
,
Kitoh
J.
,
Oda
S.
,
Kawamura
K.
(
1993
)
Obstructed migration of Purkinje cells in the developing cerebellum of the reeler mutant mouse.
Anat. Embryol
188
,
317
329
This content is only available via PDF.