Bmp activity establishes a gradient of positional information throughout the entire neural plate

Development ◽  
1999 ◽  
Vol 126 (22) ◽  
pp. 4977-4987 ◽  
Author(s):  
K.A. Barth ◽  
Y. Kishimoto ◽  
K.B. Rohr ◽  
C. Seydler ◽  
S. Schulte-Merker ◽  
...  

Bone morphogenetic proteins (Bmps) are key regulators of dorsoventral (DV) patterning. Within the ectoderm, Bmp activity has been shown to inhibit neural development, promote epidermal differentiation and influence the specification of dorsal neurons and neural crest. In this study, we examine the patterning of neural tissue in mutant zebrafish embryos with compromised Bmp signalling activity. We find that although Bmp activity does not influence anteroposterior (AP) patterning, it does affect DV patterning at all AP levels of the neural plate. Thus, we show that Bmp activity is required for specification of cell fates around the margin of the entire neural plate, including forebrain regions that do not form neural crest. Surprisingly, we find that Bmp activity is also required for patterning neurons at all DV levels of the CNS. In swirl/bmp2b(−) (swr(−)) embryos, laterally positioned sensory neurons are absent whereas more medial interneuron populations are hugely expanded. However, in somitabun(−) (sbn(−)) embryos, which probably retain higher residual Bmp activity, it is the sensory neurons and not the interneurons that are expanded. Conversely, in severely Bmp depleted embryos, both interneurons and sensory neurons are absent and it is the most medial neurons that are expanded. These results are consistent with there being a gradient of Bmp-dependent positional information extending throughout the entire neural and non-neural ectoderm.

Development ◽  
1980 ◽  
Vol 57 (1) ◽  
pp. 71-78
Author(s):  
N. B. Levy ◽  
Ann Andrew ◽  
B. B. Rawdon ◽  
Beverley Kramer

Two- to ten-somite chick embryos were studied in order to ascertain whether, as has been proposed, there exists a ‘ventral neural ridge’ which gives rise to the hypophyseal (Rathke's) pouch. Serial sections and stereo-microscopy were used. The neural ridges arch around the rostral end of the embryo onto the ventral surface of the head, but no evidence was found for their extension to form a ‘ventral neural ridge’ reaching the stomodaeum: in fact a considerable expanse of non-thickened surface ectoderm was seen to separate the ventral portions of the neural ridges from the stomodaeum. The thickening of neural ectoderm which does appear on the ventral surface of the head results from apposition and fusion of the opposite neural ridges flanking the neural plate and thus the tip of the anterior neuropore - the classically accepted mode of closure of the neuropore. These findings are in accord with the generally accepted concept of the origin of thehypophyseal pouch rather than with its derivation from a ‘ventral neural ridge’. No sign of neural crest formation was encountered ventrally; this observation excludes the possibility that endocrine cells of the APUD series could originate from neural crest in this region.


Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 525-538 ◽  
Author(s):  
M.A. Selleck ◽  
M. Bronner-Fraser

We have investigated the lineage and tissue interactions that result in avian neural crest cell formation from the ectoderm. Presumptive neural plate was grafted adjacent to non-neural ectoderm in whole embryo culture to examine the role of tissue interactions in ontogeny of the neural crest. Our results show that juxtaposition of non-neural ectoderm and presumptive neural plate induces the formation of neural crest cells. Quail/chick recombinations demonstrate that both the prospective neural plate and the prospective epidermis can contribute to the neural crest. When similar neural plate/epidermal confrontations are performed in tissue culture to look at the formation of neural crest derivatives, juxtaposition of epidermis with either early (stages 4–5) or later (stages 6–10) neural plate results in the generation of both melanocytes and sympathoadrenal cells. Interestingly, neural plates isolated from early stages form no neural crest cells, whereas those isolated later give rise to melanocytes but not crest-derived sympathoadrenal cells. Single cell lineage analysis was performed to determine the time at which the neural crest lineage diverges from the epidermal lineage and to elucidate the timing of neural plate/epidermis interactions during normal development. Our results from stage 8 to 10+ embryos show that the neural plate/neural crest lineage segregates from the epidermis around the time of neural tube closure, suggesting that neural induction is still underway at open neural plate stages.


Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 4919-4930 ◽  
Author(s):  
M.A. Selleck ◽  
M.I. Garcia-Castro ◽  
K.B. Artinger ◽  
M. Bronner-Fraser

To define the timing of neural crest formation, we challenged the fate of presumptive neural crest cells by grafting notochords, Sonic Hedgehog- (Shh) or Noggin-secreting cells at different stages of neurulation in chick embryos. Notochords or Shh-secreting cells are able to prevent neural crest formation at open neural plate levels, as assayed by DiI-labeling and expression of the transcription factor, Slug, suggesting that neural crest cells are not committed to their fate at this time. In contrast, the BMP signaling antagonist, Noggin, does not repress neural crest formation at the open neural plate stage, but does so if injected into the lumen of the closing neural tube. The period of Noggin sensitivity corresponds to the time when BMPs are expressed in the dorsal neural tube but are down-regulated in the non-neural ectoderm. To confirm the timing of neural crest formation, Shh or Noggin were added to neural folds at defined times in culture. Shh inhibits neural crest production at early stages (0-5 hours in culture), whereas Noggin exerts an effect on neural crest production only later (5-10 hours in culture). Our results suggest three phases of neurulation that relate to neural crest formation: (1) an initial BMP-independent phase that can be prevented by Shh-mediated signals from the notochord; (2) an intermediate BMP-dependent phase around the time of neural tube closure, when BMP-4 is expressed in the dorsal neural tube; and (3) a later pre-migratory phase which is refractory to exogenous Shh and Noggin.


Development ◽  
1987 ◽  
Vol 99 (3) ◽  
pp. 311-325 ◽  
Author(s):  
C.R. Kintner ◽  
D.A. Melton

We have isolated Xenopus laevis N-CAM cDNA clones and used these to study the expression of N-CAM RNA during neural induction. The results show that the first marked increase in N-CAM RNA levels occurs during gastrulation when mesoderm comes in contact with ectoderm and induces neural development. In situ hybridization results show that the early expression of N-CAM RNA is localized to the neural plate and its later expression is confined to the neural tube. Induction experiments with explanted germ layers show that N-CAM RNA is not expressed in ectoderm unless there is contact with inducing tissue. Together these results suggest an approach to studying how ectoderm is committed to form neural rather than epidermal tissue. Specifically, the data suggest that neural commitment is marked and perhaps mediated by the transcriptional activation of genes, like N-CAM, in the neural ectoderm.


Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 43-50 ◽  
Author(s):  
P. Hunt ◽  
D. Wilkinson ◽  
R. Krumlauf

The structures of the face in vertebrates are largely derived from neural crest. There is some evidence to suggest that the form of the facial pattern is determined by the crest, and that it is specified before migration as to the structures that is is able to form. The neural crest is able to control the form of surrounding, non-neural crest tissues by an instructive interaction. Some of this cranial crest is derived from a region of the hindbrain that expresses Hox 2 homeobox genes in an overlapping and segment-restricted pattern. We have found that neurogenic and mesenchymal neural crest expresses Hox 2 genes from its point of origin beside the neural plate, during migration and after migration has ceased and that rhombomeres 3 and 5 do not have any expressing neural crest beside them. Each branchial arch expresses a different combination or code of Hox genes in a segment-restricted way. The surface ectoderm over the arches initially does not express Hox genes, and later adopts an expression pattern that reflects that of neural crest that has come to underlie it. We suggest that initially the neural plate and neural crest are spatially specified, while the surface ectoderm is unpatterned. Subsequently some positional information could be transferred to the surface ectoderm as a result of an interaction with the neural crest. Given that the role of the homologous genes in insects is position specification, and that neural crest is imprinted before migration, we suggest that Hox 2 genes are providing part of this positional information to the neural crest and hence are involved in patterning the structures of the branchial arches.


Open Biology ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. 170122 ◽  
Author(s):  
Pengcheng Ma ◽  
Biyu Ren ◽  
Xiangcai Yang ◽  
Bin Sun ◽  
Xiaoliang Liu ◽  
...  

Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans. Here, we report that ZC4H2 is highly expressed in the developing neural system and is involved in neural patterning and BMP signalling in Xenopus . Knockdown of ZC4H2 led to expansion of the expression of the pan neural plate marker Sox2 in Xenopus embryos. In mammalian cells, ZC4H2 promotes BMP signalling and is involved in BMP regulated myogenic and osteogenic differentiation of mouse myoblast cells. Mechanistically, ZC4H2 binds and stabilizes Smad1 and Smad5 proteins through reducing their association with the Smurf ubiquitin ligases and thus their ubiquitination. We also found that a group of ZC4H2 mutations, which have been isolated in patients with intellectual disorders, showed weaker Smad-stabilizing activity, suggesting that the ZC4H2–Smad interaction might contribute to proper neural development in humans.


Development ◽  
2000 ◽  
Vol 127 (13) ◽  
pp. 2873-2882 ◽  
Author(s):  
R.A. Cornell ◽  
J.S. Eisen

We examined the role of Delta signaling in specification of two derivatives in zebrafish neural plate: Rohon-Beard spinal sensory neurons and neural crest. deltaA-expressing Rohon-Beard neurons are intermingled with premigratory neural crest cells in the trunk lateral neural plate. Embryos homozygous for a point mutation in deltaA, or with experimentally reduced delta signalling, have supernumerary Rohon-Beard neurons, reduced trunk-level expression of neural crest markers and lack trunk neural crest derivatives. Fin mesenchyme, a putative trunk neural crest derivative, is present in deltaA mutants, suggesting it segregates from other neural crest derivatives as early as the neural plate stage. Cranial neural crest derivatives are also present in deltaA mutants, revealing a genetic difference in regulation of trunk and cranial neural crest development.


2021 ◽  
Author(s):  
Ruth Williams ◽  
Martyna Lukoseviciute ◽  
Tatjana Sauka-Spengler ◽  
Marianne E Bronner

The epiblast of vertebrate embryos is comprised of neural and non-neural ectoderm, with the border territory at their intersection harbouring neural crest and cranial placode progenitors. Here we profile avian epiblast cells as a function of time using single-cell RNA-seq to define transcriptional changes in the emerging ‘neural plate border’. The results reveal gradual establishment of heterogeneous neural plate border signatures, including novel genes that we validate by fluorescent in situ hybridisation. Developmental trajectory analysis shows that segregation of neural plate border lineages only commences at early neurulation, rather than at gastrulation as previously predicted. We find that cells expressing the prospective neural crest marker Pax7 contribute to multiple lineages, and a subset of premigratory neural crest cells shares a transcriptional signature with their border precursors. Together, our results suggest that cells at the neural plate border remain heterogeneous until early neurulation, at which time progenitors become progressively allocated toward defined lineages.


2020 ◽  
Vol 6 (18) ◽  
pp. eaaz1469 ◽  
Author(s):  
Pierluigi Scerbo ◽  
Anne H. Monsoro-Burq

During Cambrian, unipotent progenitors located at the neural (plate) border (NB) of an Olfactoria chordate embryo acquired the competence to form ectomesenchyme, pigment cells and neurons, initiating the rise of the multipotent neural crest cells (NC) specific to vertebrates. Surprisingly, the known vertebrate NB/NC transcriptional circuitry is a constrained feature also found in invertebrates. Therefore, evidence for vertebrate-specific innovations endowing vertebrate NC with multipotency is still missing. Here, we identified VENTX/NANOG and POU5/OCT4 as vertebrate-specific innovations. When VENTX was depleted in vivo and in directly-induced NC, the NC lost its early multipotent state and its skeletogenic potential, but kept sensory neuron and pigment identity, thus reminiscent of invertebrate NB precursors. In vivo, VENTX gain-of-function enabled NB specifiers to reprogram embryonic non-neural ectoderm towards early NC identity. We propose that skeletogenic NC evolved by acquiring VENTX/NANOG activity, promoting a novel multipotent progenitor regulatory state into the pre-existing sensory neuron/pigment NB program.


Development ◽  
1999 ◽  
Vol 126 (18) ◽  
pp. 3969-3979 ◽  
Author(s):  
K.B. Artinger ◽  
A.B. Chitnis ◽  
M. Mercola ◽  
W. Driever

In the developing vertebrate nervous system, both neural crest and sensory neurons form at the boundary between non-neural ectoderm and the neural plate. From an in situ hybridization based expression analysis screen, we have identified a novel zebrafish mutation, narrowminded (nrd), which reduces the number of early neural crest cells and eliminates Rohon-Beard (RB) sensory neurons. Mosaic analysis has shown that the mutation acts cell autonomously suggesting that nrd is involved in either the reception or interpretation of signals at the lateral neural plate boundary. Characterization of the mutant phenotype indicates that nrd is required for a primary wave of neural crest cell formation during which progenitors generate both RB sensory neurons and neural crest cells. Moreover, the early deficit in neural crest cells in nrd homozygotes is compensated later in development. Thus, we propose that a later wave can compensate for the loss of early neural crest cells but, interestingly, not the RB sensory neurons. We discuss the implications of these findings for the possibility that RB sensory neurons and neural crest cells share a common evolutionary origin.


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