XASH-3, a novel Xenopus achaete-scute homolog, provides an early marker of planar neural induction and position along the mediolateral axis of the neural plate

We have isolated a novel Xenopus homolog of the Drosophila achaete-scute genes, called XASH-3. XASH-3 expression is neural specific and is detected as early as stage 11 1/2, making it one of the earliest markers of neural induction so far described. Moreover, XASH-3 expression within the neural plate is regionally restricted. Transverse bands of XASH-3 mRNA mark discrete positions along the anteroposterior axis, while longitudinal bands mark a discrete position along the mediolateral axis. This latter site of XASH-3 expression appears to demarcate the prospective sulcus limitans, a boundary zone that later separates the functionally distinct dorsal (alar) and ventral (basal) regions of the spinal cord. In sandwich explants lacking any underlying mesoderm, XASH-3 is expressed in longitudinal stripes located lateral to the midline. This provides the first indication that planar or midline-derived inductive signals are sufficient to establish at least some aspects of positional identity along the mediolateral axis of the neural plate. By contrast, the transverse stripes of XASH-3 expression are not detected, suggesting that this aspect of anteroposterior neural pattern is lost or delayed in the absence of vertically passed signals. The restricted mediolateral expression of XASH-3 suggests that mediolateral patterning of the neural plate is an early event, and that this regionalization can be achieved in the absence of inducing signals derived from underlying mesoderm.

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Neural induction and regionalisation in the chick embryo

Development ◽

10.1242/dev.114.3.729 ◽

1992 ◽

Vol 114 (3) ◽

pp. 729-741 ◽

Cited By ~ 41

Author(s):

K.G. Storey ◽

J.M. Crossley ◽

E.M. De Robertis ◽

W.E. Norris ◽

C.D. Stern

Keyword(s):

Spinal Cord ◽

Nervous System ◽

Molecular Markers ◽

Chick Embryo ◽

Normal Development ◽

Neural Induction ◽

Stage 4 ◽

Embryo Chick ◽

Host Embryo ◽

Embryonic Region

Induction and regionalisation of the chick nervous system were investigated by transplanting Hensen's node into the extra-embryonic region (area opaca margin) of a host embryo. Chick/quail chimaeras were used to determine the contributions of host and donor tissue to the supernumerary axis, and three molecular markers, Engrailed, neurofilaments (antibody 3A10) and XlHbox1/Hox3.3 were used to aid the identification of particular regions of the ectopic axis. We find that the age of the node determines the regions of the nervous system that form: young nodes (stages 2–4) induced both anterior and posterior nervous system, while older nodes (stages 5–6) have reduced inducing ability and generate only posterior nervous system. By varying the age of the host embryo, we show that the competence of the epiblast to respond to neural induction declines after stage 4. We conclude that during normal development, the initial steps of neural induction take place before stage 4 and that anteroposterior regionalisation of the nervous system may be a later process, perhaps associated with the differentiating notochord. We also speculate that the mechanisms responsible for induction of head CNS differ from those that generate the spinal cord: the trunk CNS could arise by homeogenetic induction by anterior CNS or by elongation of neural primordia that are induced very early.

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Mechanism of anteroposterior axis specification in vertebrates. Lessons from the amphibians

Development ◽

10.1242/dev.114.2.285 ◽

1992 ◽

Vol 114 (2) ◽

pp. 285-302 ◽

Cited By ~ 33

Author(s):

J.M. Slack ◽

D. Tannahill

Keyword(s):

Molecular Markers ◽

Expression Patterns ◽

Signal Transduction Pathway ◽

Homeobox Gene ◽

Neural Induction ◽

High Sensitivity ◽

Neural Plate ◽

Mesoderm Induction ◽

Inducing Factors ◽

Almost All

Interest in the problem of anteroposterior specification has quickened because of our near understanding of the mechanism in Drosophila and because of the homology of Antennapedia-like homeobox gene expression patterns in Drosophila and vertebrates. But vertebrates differ from Drosophila because of morphogenetic movements and interactions between tissue layers, both intimately associated with anteroposterior specification. The purpose of this article is to review classical findings and to enquire how far these have been confirmed, refuted or extended by modern work. The “pre-molecular” work suggests that there are several steps to the process: (i) Formation of anteroposterior pattern in mesoderm during gastrulation with posterior dominance. (ii) Regional specific induction of ectoderm to form neural plate. (iii) Reciprocal interactions from neural plate to mesoderm. (iv) Interactions within neural plate with posterior dominance. Unfortunately, almost all the observable markers are in the CNS rather than in the mesoderm where the initial specification is thought to occur. This has meant that the specification of the mesoderm has been assayed indirectly by transplantation methods such as the Einsteckung. New molecular markers now supplement morphological ones but they are still mainly in the CNS and not the mesoderm. A particular interest attaches to the genes of the Antp-like HOX clusters since these may not only be markers but actual coding factors for anteroposterior levels. We have a new understanding of mesoderm induction based on the discovery of activins and fibroblast growth factors (FGFs) as candidate inducing factors. These factors have later consequences for anteroposterior pattern with activin tending to induce anterior, and FGF posterior structures. Recent work on neural induction has implicated cAMP and protein kinase C (PKC) as elements of the signal transduction pathway and has provided new evidence for the importance of tangential neural induction. The regional specificity of neural induction has been reinvestigated using molecular markers and provides conclusions rather similar to the classical work. Defects in the axial pattern may be produced by retinoic acid but it remains unclear whether its effects are truly coordinate ones or are concentrated in certain regions of high sensitivity. In general the molecular studies have supported and reinforced the “pre-molecular ones”. Important questions still remain: (i) How much pattern is there in the mesoderm (how many states?) (ii) How is this pattern generated by the invaginating organizer? (iii) Is there one-to-one transmission of codings to the neural plate? (iv) What is the nature of the interactions within the neural plate? (v) Are the HOX cluster genes really the anteroposterior codings?

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FGF signalling controls the timing of Pax6 activation in the neural tube

Development ◽

10.1242/dev.127.22.4837 ◽

2000 ◽

Vol 127 (22) ◽

pp. 4837-4843 ◽

Cited By ~ 1

Author(s):

N. Bertrand ◽

F. Medevielle ◽

F. Pituello

Keyword(s):

Spinal Cord ◽

Neural Tube ◽

Inhibitory Activity ◽

Neural Plate ◽

Presomitic Mesoderm ◽

Pax6 Expression ◽

Epithelial Development ◽

Repressive Effect ◽

Caudal Regression ◽

Fgf Signalling

We have recently demonstrated that Pax6 activation occurs in phase with somitogenesis in the spinal cord. Here we show that the presomitic mesoderm exerts an inhibitory activity on Pax6 expression. This repressive effect is mediated by the FGF signalling pathway. The presomitic mesoderm displays a decreasing caudorostral gradient of FGF8, and grafting FGF8-soaked beads at the level of the neural tube abolishes Pax6 activation. Conversely, when FGF signalling is disrupted, Pax6 is prematurely activated in the neural plate. We propose that the progression of Pax6 activation in the neural tube is controlled by the caudal regression of the anterior limit of FGF activity. Hence, as part of its posteriorising activity, FGF8 downregulation acts as a switch from early (posterior) to a later (anterior) state of neural epithelial development.

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Neural Activation and Transformation in Explants of Competent Ectoderm under the Influence of Fragments of Anterior Notochord in Urodeles

Development ◽

10.1242/dev.2.3.175 ◽

1954 ◽

Vol 2 (3) ◽

pp. 175-193

Author(s):

P. D. Nieuwkoop ◽

G. v. Nigtevecht

Keyword(s):

Spinal Cord ◽

Neural Induction ◽

Spatial Relations ◽

Neural Activation ◽

Stages Of Development ◽

Temporal And Spatial ◽

Pass Through ◽

Autonomous Development

Experiments in which folds of competent ectoderm were attached to neural plates of host embryos at various cranio-caudal levels (Nieuwkoop et al., 1952) suggested that two successive influences emanate from the underlying archenteron roof: a first one representing a more or less non-specific activation which leads autonomously to a differentiation in a prosencephalic direction; and a second one transforming these prosencephalic differentiation tendencies into more caudal ones leading to the formation of rhombencephalon and spinal cord. The work of Eyal-Giladi (1954) in which the temporal and spatial relations of neural induction were analysed by means of an interruption of the induction at various stages of development and at various cranio-caudal levels of the presumptive neural area showed very clearly that during gastrulation two successive waves of induction actually pass through the presumptive neuro-ectoderm in a caudo-cranial direction. The first wave, which emanates from the presumptive prechordal material, leads to an activation of the ectoderm and its autonomous development in a prosencephalic direction.

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Neurodevelopment

New Oxford Textbook of Psychiatry ◽

10.1093/med/9780198713005.003.0011 ◽

2020 ◽

pp. 91-100

Author(s):

Karl Zilles ◽

Nicola Palomero-Gallagher

Keyword(s):

Spinal Cord ◽

Nervous System ◽

Neural Tube ◽

Neural Plate ◽

Adult Brain ◽

The Central Nervous System ◽

Specialized Region ◽

The Brain ◽

Rostral Part ◽

Human Nervous System

The pre- and post-natal development of the human nervous system is briefly described, with special emphasis on the brain, particularly the cerebral and cerebellar cortices. The central nervous system originates from a specialized region of the ectoderm—the neural plate—which develops into the neural tube. The rostral part of the neural tube forms the adult brain, whereas the caudal part (behind the fifth somite) differentiates into the spinal cord. The embryonic brain has three vesicular enlargements: the forebrain, the midbrain, and the hindbrain. The histogenesis of the spinal cord, hindbrain, cerebellum, and cerebral cortex, including myelination, is discussed. The chapter closes with a description of the development of the hemispheric shape and the formation of gyri.

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Neural Induction, Neural Fate Stabilization, and Neural Stem Cells

The Scientific World JOURNAL ◽

10.1100/tsw.2002.217 ◽

2002 ◽

Vol 2 ◽

pp. 1147-1166 ◽

Cited By ~ 10

Author(s):

Sally A. Moody ◽

Hyun-Soo Je

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Neural Stem Cells ◽

Neural Development ◽

Current Knowledge ◽

Embryonic Stem ◽

Neural Induction ◽

Neural Plate ◽

Natural Rate ◽

Neural Fate

The promise of stem cell therapy is expected to greatly benefit the treatment of neurodegenerative diseases. An underlying biological reason for the progressive functional losses associated with these diseases is the extremely low natural rate of self-repair in the nervous system. Although the mature CNS harbors a limited number of self-renewing stem cells, these make a significant contribution to only a few areas of brain. Therefore, it is particularly important to understand how to manipulate embryonic stem cells and adult neural stem cells so their descendants can repopulate and functionally repair damaged brain regions. A large knowledge base has been gathered about the normal processes of neural development. The time has come for this information to be applied to the problems of obtaining sufficient, neurally committed stem cells for clinical use. In this article we review the process of neural induction, by which the embryonic ectodermal cells are directed to form the neural plate, and the process of neural�fate stabilization, by which neural plate cells expand in number and consolidate their neural fate. We will present the current knowledge of the transcription factors and signaling molecules that are known to be involved in these processes. We will discuss how these factors may be relevant to manipulating embryonic stem cells to express a neural fate and to produce large numbers of neurally committed, yet undifferentiated, stem cells for transplantation therapies.

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