The trunk neural crest of vertebrate embryos is a transient collection of precursor cells present along the dorsal aspect of the neural tube. These cells migrate on two distinct pathways and give rise to specific derivatives in precise embryonic locations. One group of crest cells migrates early on a ventral pathway and generates neurons and glial cells. A later-dispersing group migrates laterally and gives rise to melanocytes in the skin. These observations raise the possibility that the appearance of distinct derivatives in different embryonic locations is a consequence of lineage restrictions specified before or soon after the onset of neural crest cell migration. To test this notion, we have assessed when and in what order distinct cell fates are specified during neural crest development. We determined the proportions of different types of precursor cells in cultured neural crest populations immediately after emergence from the neural tube and at intervals as development proceeds. We found that the initial neural crest population was a heterogeneous mixture of precursors almost half of which generated single-phenotype clones. Distinct neurogenic and melanogenic sublineages were also present in the outgrowth population almost immediately, but melanogenic precursors dispersed from the neural tube only after many neurogenic precursors had already done so. A discrete fate-restricted neuronal precursor population was distinguished before entirely separate fate-restricted melanocyte and glial precursor populations were present, and well before initial neuronal differentiation. Taken together, our results demonstrate that lineage-restricted subpopulations constitute a major portion of the initial neural crest population and that neural crest diversification occurs well before overt differentiation by the asynchronous restriction of distinct cell fates. Thus, the different morphogenetic and differentiative behavior of neural crest subsets in vivo may result from earlier cell fate-specification events that generate developmentally distinct subpopulations that respond differentially to environmental cues.

REFERENCES

Anderson
D. J.
,
Axel
R.
(
1986
)
A bipotential neuroendocrine precursor whose choice of cell fate is determined by NGF and glucocorticoids.
Cell
47
,
1079
1090
Baroffio
A.
,
Dupin
E.
,
Le Douarin
N. M.
(
1988
)
Clone-forming ability and differentiation potential of migratory neural crest cells.
Proc. Natl. Acad. Sci. USA
85
,
5325
5329
Baroffio
A.
,
Dupin
E.
,
Le Douarin
N. M.
(
1991
)
Common precursors for neural and mesectodermal derivatives in the cephalic neural crest.
Development
112
,
301
305
Bronner-Fraser
M.
,
Fraser
S.
(
1988
)
Cell lineage analysis reveals multipotency of some avian neural crest cells.
Nature
355
,
161
164
Davidson
E. H.
(
1990
)
How embryos work: a comparative view of diverse modes of cell fate specification.
Development
108
,
365
389
Dupin
E.
,
Baroffio
A.
,
Dulac
C.
,
Cameron-Curry
P.
,
Le Douarin
N. M.
(
1990
)
Schwann-cell differentiation in clonal cultures of the neural crest, as evidenced by the anti-Schwann cell myelin protein monoclonal antibody.
Proc. Natl. Acad. Sci. USA
87
,
1119
1123
Erickson
C. A.
,
Duong
T. D.
,
Tosney
K. W.
(
1992
)
Descriptive and experimental analysis of the dispersion of neural crest cells along the dorsolateral path and their entry into ectoderm in the chick embryos.
Dev. Biol
151
,
251
272
Erickson
C. A.
,
Perris
R.
(
1993
)
The role of cell-cell and cell-matrix interactions in the morphogenesis of the neural crest.
Dev. Biol
159
,
60
74
Erickson
C. A.
,
Goins
T. L.
(
1995
)
Avian neural crest cells can migrate on the dorsolateral path only if they are specified as melanocytes.
Development
121
,
915
924
Fagotto
F.
,
Gumbiner
B. M.
(
1996
)
Cell contact-dependent Signaling.
Dev. Biol
180
,
445
454
Frank
E.
,
Sanes
J. R.
(
1991
)
Lineage of neurons and glia in chick dorsal root ganglia: analysis in vivo with a recombinant retrovirus.
Development
111
,
895
908
Fraser
S. E.
,
Bronner-Fraser
M.
(
1991
)
Migrating neural crest cells in the trunk of avian embryos are multipotent.
Development
112
,
913
920
Girdlestone
J.
,
Weston
J. A.
(
1985
)
Identification of early neuronal subpopulations in avian neural crest cell cultures.
Dev. Biol
109
,
274
287
Henion
P. D.
,
Landis
S. C.
(
1992
)
Developmental regulation of leucine-enkephalin expression in adrenal chromaffin cells by glucocorticoids and innervation.
J. Neurosci
12
,
3818
3827
Henion
P. D.
,
Weston
J. A.
(
1994
)
Retinoic acid selectively promotes the survival and proliferation of neurogenic precursors in cultured neural crest cell populations.
Dev. Biol
161
,
243
250
Henion
P. D.
,
Garner
A. S.
,
Large
T. H.
,
Weston
J. A.
(
1995
)
trk C-mediated NT-3 signaling is required for the early development of a subpopulation of neurogenic neural crest cells.
Dev. Biol
172
,
602
613
Hökfelt
T.
,
Johansson
O.
,
Ljungdahl
,
Lundberg
J.
,
Schultzberg
M.
(
1980
)
Peptidergic neurones.
Nature
284
,
515
521
Ito
K.
,
Sieber-Blum
M.
(
1991
)
In vitro clonal analysis of quail cardiac neural crest development.
Dev. Biol
148
,
95
106
Kahane
N.
,
Kalcheim
C.
(
1994
)
Expression of trkC receptor mRNA during development of the avian nervous system.
J. Neurobiol
25
,
571
584
Kitamura
K.
,
Takiguchi-Hayashi
K.
,
Sezaki
M.
,
Yamamoto
H.
,
Tekeuchi
T.
(
1992
)
Avian neural crest cells express a melanogenic trait during early migration from the neural tube: observations with the new monoclonal antibody MEBL-1.
Development
114
,
367
378
Le Douarin
N.
,
Ziller
C.
,
Couly
G.
(
1993
)
Patterning of neural crest derivatives in the avian embryo: In vivo and in vitro studies.
Dev. Biol
159
,
24
49
Marusich
M. F.
,
Weston
J. A.
(
1992
)
Identification of early neurogenic cells in the neural crest lineage.
Dev. Biol
149
,
295
306
Marusich
M.
,
Pourmehr
K.
,
Weston
J. A.
(
1986
)
A monoclonal antibody (SN1) identifies a subpopulation of avian sensory neurons whose distribution is correlated with axial level.
Dev. Biol
118
,
494
504
Marusich
M. F.
,
Furneaux
H. M.
,
Henion
P. D.
,
Weston
J. A.
(
1994
)
Hu neuronal proteins are expressed in proliferating Neurogenic Cells.
J. Neurobiol
25
,
143
155
Maxwell
G.
(
1976
)
Cell cycle changes during neural crest cell differentiation in vitro.
Dev. Biol
49
,
66
79
Oakley
R. A.
,
Lasky
C. J.
,
Erickson
C. A.
,
Tosney
K. W.
(
1994
)
Glycoconjugates mark a transient barrier to neural crest migration in the chicken embryo.
Development
120
,
103
114
Raible
D. W.
,
Eisen
J. S.
(
1994
)
Restriction of neural crest cell fate in the trunk of the embryonic zebrafish.
Development
120
,
495
503
Reedy
M. V.
,
Faraco
C. D.
,
Erickson
C. A.
(
1997
)
Temporal differences in developmental potential underlie the unique morphogenetic behaviors of early-and late-migrating avian trunk neural crest cells.
Dev. Biol
186
,
322
–.
Schilling
T. F.
,
Kimmel
C. B.
(
1994
)
Segment and cell type lineage restrictions during pharyngeal arch development in the zebrafish embryo.
Development
120
,
483
494
Selleck
M.
,
Scherson
T.
,
Bronner-Fraser
M.
(
1993
)
Origins of neural crest cell diversity.
Dev. Biol
159
,
1
11
Serbedzija
G. N.
,
Bronner-Fraser
M.
,
Fraser
S. E.
(
1989
)
A vital dye analysis of the timing and pathways of neural crest cell migration.
Development
106
,
809
819
Serbedzija
G. N.
,
Bronner-Fraser
M.
,
Fraser
S. E.
(
1994
)
Developmental potential of trunk neural crest cells in the mouse.
Development
120
,
1709
1718
Shah
N. M.
,
Marchionni
M. A.
,
Isaacs
I.
,
Stroobant
P.
,
Anderson
D. J.
(
1994
)
Glial growth factor restricts mammalian neural crest stem cells to a glial fate.
Cell
77
,
349
360
Shah
N. M.
,
Groves
A. K.
,
Anderson
D. J.
(
1996
)
Alternative neural crest cell fates are instructively promoted by TGFsuperfamily members.
Cell
85
,
331
343
Sieber-Blum
M.
,
Cohen
A.
(
1980
)
Clonal analysis of quail neural crest cells: They are pluripotent and differentiate in vitro in the absence of non-neuronal crest cells.
Dev. Biol
80
,
96
106
Sieber-Blum
M.
(
1989
)
Commitment of neural crest cells to the sensory neuron lineage.
Science
243
,
1608
1611
Stemple
D. L.
,
Anderson
D. J.
(
1992
)
Isolation of a stem cell for neurons and glia from the mammalian neural crest.
Cell
71
,
973
985
Stemple
D. L.
,
Anderson
D. J.
(
1993
)
Lineage diversification of the neural crest: In vitro investigations.
Dev. Biol
159
,
12
23
Tanaka
H.
,
Agata
A.
,
Obata
K.
(
1989
)
A new membrane antigen revealed by monoclonal antibodies is associated with motoneuron axonal pathways.
Dev. Biol
132
,
419
435
Tessarollo
L.
,
Tsouflas
P.
,
Martin-Zanca
D.
,
Gilbert
D. J.
,
Jenkins
N. A.
,
Copeland
N. G.
,
Parada
L. F.
(
1993
)
trkC, a receptor forneurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues.
Development
118
,
463
475
Verdi
J. M.
,
Groves
A. K.
,
Farinas
I.
,
Jones
K.
,
Marchionni
M. A.
,
Reichardt
L. F.
,
Anderson
D. J.
(
1996
)
A reciprocal cell-cell interaction mediated by NT-3 and neuregulins controls the early survival and development of sympathetic neuroblasts.
Neuron
16
,
515
527
Vogel
K. S.
,
Weston
J. A.
(
1988
)
A subpopulation of cultured avian neural crest cells has transient neurogenic potential.
Neuron
1
,
569
577
Vogel
K. S.
,
Weston
J. A.
(
1990
)
The sympathoadrenal lineage in avian embryos.
Dev. Biol
139
,
1
12
Wehrle-Haller
B.
,
Weston
J. A.
(
1995
)
Soluble and cell-bound forms of steel factor activity play distinct roles in melanocyte precursor dispersal and survival on the lateral neural crest migration pathway.
Development
121
,
731
742
Weston
J. A.
(
1991
)
Sequential segregation and fate of developmentally restricted intermediate cell populations in the neural crest lineage.
Curr. Top. Dev. Biol
25
,
133
153
Yao
K.-M.
,
Samson
M.-L.
,
Reeves
R.
,
White
K.
(
1993
)
Gene elav of Drosophila melanogaster: a prototype for neuronal-specific RNA binding protein gene family that is conserved in flies and humans.
J. Neurobiol
24
,
723
739
Zacchei
A. M.
(
1961
)
Lo sviluppo embrionale della quaglia giapponese (Coturnix coturnix japonica).
Arch. Ital. Anat. Embriol
66
,
36
72
Zhang
D.
,
Yao
L.
,
Bernd
P.
(
1994
)
Expression of trk and neurotrophin mRNA in dorsal root and sympathetic ganglia of the quail during development.
J. Neurobiol
25
,
1517
1532
This content is only available via PDF.