Foxa2 mediates critical functions of prechordal plate in patterning and morphogenesis and is cell autonomously required for early ventral endoderm morphogenesis

We have investigated axis-inducing activities and cellular fates of the zebrafish organizer using a new method of transplantation that allows the transfer of both deep and superficial organizer tissues. Previous studies have demonstrated that the zebrafish embryonic shield possesses classically defined dorsal organizer activity. When we remove the morphologically defined embryonic shield, embryos recover and are completely normal by 24 hours post-fertilization. We find that removal of the morphological shield does not remove all goosecoid- and floating head-expressing cells, suggesting that the morphological shield does not comprise the entire organizer region. Complete removal of the embryonic shield and adjacent marginal tissue, however, leads to a loss of both prechordal plate and notochord. In addition, these embryos are cyclopean, show a significant loss of floor plate and primary motorneurons and display disrupted somite patterning. Motivated by apparent discrepancies in the literature we sought to test the axis-inducing activity of the embryonic shield. A previous study suggested that the shield is capable of only partial axis induction, specifically being unable to induce the most anterior neural tissues. Contrary to this study, we find shields can induce complete secondary axes when transplanted into host ventral germ-ring. In induced secondary axes donor tissue contributes to notochord, prechordal plate and floor plate. When explanted shields are divided into deep and superficial fragments and separately transplanted we find that deep tissue is able to induce the formation of ectopic axes with heads but lacking posterior tissues. We conclude that the deep tissue included in our transplants is important for proper head formation.

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Inductive patterning of the embryonic brain in Drosophila

Development ◽

10.1242/dev.129.9.2121 ◽

2002 ◽

Vol 129 (9) ◽

pp. 2121-2128

Author(s):

Damon T. Page

Keyword(s):

Brain Development ◽

Common Ancestor ◽

Last Common Ancestor ◽

Embryonic Brain ◽

Germ Layers ◽

Brain Anomaly ◽

Prechordal Plate ◽

Foregut Endoderm ◽

The Brain ◽

Brain Patterning

In vertebrates (deuterostomes), brain patterning depends on signals from adjacent tissues. For example, holoprosencephaly, the most common brain anomaly in humans, results from defects in signaling between the embryonic prechordal plate (consisting of the dorsal foregut endoderm and mesoderm) and the brain. I have examined whether a similar mechanism of brain development occurs in the protostome Drosophila, and find that the foregut and mesoderm act to pattern the fly embryonic brain. When the foregut and mesoderm of Drosophila are ablated, brain patterning is disrupted. The loss of Hedgehog expressed in the foregut appears to mediate this effect, as it does in vertebrates. One mechanism whereby these defects occur is a disruption of normal apoptosis in the brain. These data argue that the last common ancestor of protostomes and deuterostomes had a prototype of the brains present in modern animals, and also suggest that the foregut and mesoderm contributed to the patterning of this ‘proto-brain’. They also argue that the foreguts of protostomes and deuterostomes, which have traditionally been assigned to different germ layers, are actually homologous.

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A single morphogenetic field gives rise to two retina primordia under the influence of the prechordal plate

Development ◽

10.1242/dev.124.3.603 ◽

1997 ◽

Vol 124 (3) ◽

pp. 603-615 ◽

Cited By ~ 38

Author(s):

H. Li ◽

C. Tierney ◽

L. Wen ◽

J.Y. Wu ◽

Y. Rao

Keyword(s):

Expression Pattern ◽

Lineage Tracing ◽

Chick Embryos ◽

Median Region ◽

Prechordal Plate ◽

Prechordal Mesoderm ◽

New Gene ◽

Vertebrate Embryos ◽

Migration Of Cells ◽

Anterior Neural Plate

Two bilaterally symmetric eyes arise from the anterior neural plate in vertebrate embryos. An interesting question is whether both eyes share a common developmental origin or they originate separately. We report here that the expression pattern of a new gene ET reveals that there is a single retina field which resolves into two separate primordia, a suggestion supported by the expression pattern of the Xenopus Pax-6 gene. Lineage tracing experiments demonstrate that retina field resolution is not due to migration of cells in the median region to the lateral parts of the field. Removal of the prechordal mesoderm led to formation of a single retina both in chick embryos and in Xenopus explants. Transplantation experiments in chick embryos indicate that the prechordal plate is able to suppress Pax-6 expression. Our results provide direct evidence for the existence of a single retina field, indicate that the retina field is resolved by suppression of retina formation in the median region of the field, and demonstrate that the prechordal plate plays a primary signaling role in retina field resolution.

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Inductive interactions direct early regionalization of the mouse forebrain

Development ◽

10.1242/dev.124.14.2709 ◽

1997 ◽

Vol 124 (14) ◽

pp. 2709-2718 ◽

Cited By ~ 68

Author(s):

K. Shimamura ◽

J.L. Rubenstein

Keyword(s):

Sonic Hedgehog ◽

Bone Morphogenetic Proteins ◽

Molecular Mechanisms ◽

Neural Plate ◽

Gene Encoding ◽

Prechordal Plate ◽

Optic Vesicles ◽

The Central Nervous System ◽

Anterior Neural Plate ◽

Anterior Posterior

The cellular and molecular mechanisms that regulate regional specification of the forebrain are largely unknown. We studied the expression of transcription factors in neural plate explants to identify tissues, and the molecules produced by these tissues, that regulate medial-lateral and local patterning of the prosencephalic neural plate. Molecular properties of the medial neural plate are regulated by the prechordal plate perhaps through the action of Sonic Hedgehog. By contrast, gene expression in the lateral neural plate is regulated by non-neural ectoderm and bone morphogenetic proteins. This suggests that the forebrain employs the same medial-lateral (ventral-dorsal) patterning mechanisms present in the rest of the central nervous system. We have also found that the anterior neural ridge regulates patterning of the anterior neural plate, perhaps through a mechanism that is distinct from those that regulate general medial-lateral patterning. The anterior neural ridge is essential for expression of BF1, a gene encoding a transcription factor required for regionalization and growth of the telencephalic and optic vesicles. In addition, the anterior neural ridge expresses Fgf8, and recombinant FGF8 protein is capable of inducing BF1, suggesting that FGF8 regulates the development of anterolateral neural plate derivatives. Furthermore, we provide evidence that the neural plate is subdivided into distinct anterior-posterior domains that have different responses to the inductive signals from the prechordal plate, Sonic Hedgehog, the anterior neural ridge and FGF8. In sum, these results suggest that regionalization of the forebrain primordia is established by several distinct patterning mechanisms: (1) anterior-posterior patterning creates transverse zones with differential competence within the neural plate, (2) patterning along the medial-lateral axis generates longitudinally aligned domains and (3) local inductive interactions, such as a signal(s) from the anterior neural ridge, further define the regional organization.

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Distinct and cooperative roles for Nodal and Hedgehog signals during hypothalamic development

Development ◽

10.1242/dev.129.13.3055 ◽

2002 ◽

Vol 129 (13) ◽

pp. 3055-3065 ◽

Cited By ~ 5

Author(s):

Juliette Mathieu ◽

Anukampa Barth ◽

Frederic M. Rosa ◽

Stephen W. Wilson ◽

Nadine Peyriéras

Keyword(s):

Signaling Pathways ◽

Hedgehog Signaling ◽

Evolutionary Conservation ◽

Neural Plate ◽

Nodal Signaling ◽

Functional Importance ◽

Anterior Dorsal ◽

Site Of Action ◽

Prechordal Plate ◽

Further Development

Despite its evolutionary conservation and functional importance, little is known of the signaling pathways that underlie development of the hypothalamus. Although mutations affecting Nodal and Hedgehog signaling disrupt hypothalamic development, the time and site of action and the exact roles of these pathways remain very poorly understood. Unexpectedly, we show here that cell-autonomous reception of Nodal signals is neither required for the migration of hypothalamic precursors within the neural plate, nor for further development of the anterior-dorsal hypothalamus. Nodal signaling is, however, cell-autonomously required for establishment of the posterior-ventral hypothalamus. Conversely, Hedgehog signaling antagonizes the development of posterior-ventral hypothalamus, while promoting anterior-dorsal hypothalamic fates. Besides their distinct roles in the regionalization of the diencephalon, we reveal cooperation between Nodal and Hedgehog pathways in the maintenance of the anterior-dorsal hypothalamus. Finally we show that it is the prechordal plate and not the head endoderm that provides the early signals essential for establishment of the hypothalamus.

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The role of Xenopus dickkopf1 in prechordal plate specification and neural patterning

Development ◽

10.1242/dev.127.22.4981 ◽

2000 ◽

Vol 127 (22) ◽

pp. 4981-4992 ◽

Cited By ~ 8

Author(s):

O. Kazanskaya ◽

A. Glinka ◽

C. Niehrs

Keyword(s):

Target Genes ◽

Loss Of Function ◽

Dorsoventral Patterning ◽

Gastrula Stage ◽

Neural Patterning ◽

Prechordal Plate ◽

Wnt Inhibitor ◽

The Central Nervous System ◽

Wnt Inhibitors

Dickkopf1 (dkk1) encodes a secreted WNT inhibitor expressed in Spemann's organizer, which has been implicated in head induction in Xenopus. Here we have analyzed the role of dkk1 in endomesoderm specification and neural patterning by gain- and loss-of-function approaches. We find that dkk1, unlike other WNT inhibitors, is able to induce functional prechordal plate, which explains its ability to induce secondary heads with bilateral eyes. This may be due to differential WNT inhibition since dkk1, unlike frzb, inhibits Wnt3a signalling. Injection of inhibitory antiDkk1 antibodies reveals that dkk1 is not only sufficient but also required for prechordal plate formation but not for notochord formation. In the neural plate dkk1 is required for anteroposterior and dorsoventral patterning between mes- and telencephalon, where dkk1 promotes anterior and ventral fates. Both the requirement of anterior explants for dkk1 function and their ability to respond to dkk1 terminate at late gastrula stage. Xenopus embryos posteriorized with bFGF, BMP4 and Smads are rescued by dkk1. dkk1 does not interfere with the ability of bFGF to induce its immediate early target gene Xbra, indicating that its effect is indirect. In contrast, there is cross-talk between BMP and WNT signalling, since induction of BMP target genes is sensitive to WNT inhibitors until the early gastrula stage. Embryos treated with retinoic acid (RA) are not rescued by dkk1 and RA affects the central nervous system (CNS) more posterior than dkk1, suggesting that WNTs and retinoids may act to pattern anterior and posterior CNS, respectively, during gastrulation.

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