Inductive interactions direct early regionalization of the mouse forebrain

Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2709-2718 ◽  
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.

Longitudinal organization of the anterior neural plate and neural tube

Development ◽  
1995 ◽  
Vol 121 (12) ◽  
pp. 3923-3933 ◽  
Author(s):  
K. Shimamura ◽  
D.J. Hartigan ◽  
S. Martinez ◽  
L. Puelles ◽  
J.L. Rubenstein
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Longitudinal Axis ◽  
Neural Plate ◽  
Molecular Properties ◽  
Spatially Correlated ◽  
Longitudinal Axon ◽  
Embryonic Cns ◽  
Anterior Neural Plate ◽  
Anterior Posterior

Over the last century, several morphological models of forebrain organization have been proposed that hypothesize alternative topological solutions for the relationships of the histogenic primordia. Central to all of these models are their definitions of the longitudinal axis and the longitudinal organization of the neural plate and neural tube. To understand the longitudinal organization of the anterior brain, we have sought to identify molecular properties that are continuous along the entire longitudinal axis of the embryonic CNS. In this essay, we describe studies of the expression of several genes in the mouse between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide evidence for the trajectory of the anterior-posterior axis and the longitudinal organization of the anterior CNS. Specifically, we report that the expression of noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are present along the entire CNS axis. Within the forebrain, the expression of these genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions in the neural plate and tube. We demonstrate that the earliest longitudinal axon pathways of the forebrain are spatially correlated with the longitudinal domain defined by Nkx-2.2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic neural plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the neural plate.

scholarly journals Hallmarks of primary neurulation are conserved in the zebrafish forebrain

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jonathan M. Werner ◽  
Maraki Y. Negesse ◽  
Dominique L. Brooks ◽  
Allyson R. Caldwell ◽  
Jafira M. Johnson ◽  
...  
Keyword(s):  
Neural Tube ◽  
Time Lapse ◽  
Neural Plate ◽  
Neural Tube Closure ◽  
Developmental Studies ◽  
Underlying Causes ◽  
The Central Nervous System ◽  
Resolution Imaging ◽  
Fold Formation ◽  
Anterior Neural Plate

AbstractPrimary neurulation is the process by which the neural tube, the central nervous system precursor, is formed from the neural plate. Incomplete neural tube closure occurs frequently, yet underlying causes remain poorly understood. Developmental studies in amniotes and amphibians have identified hingepoint and neural fold formation as key morphogenetic events and hallmarks of primary neurulation, the disruption of which causes neural tube defects. In contrast, the mode of neurulation in teleosts has remained highly debated. Teleosts are thought to have evolved a unique mode of neurulation, whereby the neural plate infolds in absence of hingepoints and neural folds, at least in the hindbrain/trunk where it has been studied. Using high-resolution imaging and time-lapse microscopy, we show here the presence of these morphological landmarks in the zebrafish anterior neural plate. These results reveal similarities between neurulation in teleosts and other vertebrates and hence the suitability of zebrafish to understand human neurulation.

scholarly journals Zebrafish Dkk1, induced by the pre-MBT Wnt signaling, is secreted from the prechordal plate and patterns the anterior neural plate

2000 ◽  
Vol 98 (1-2) ◽  
pp. 3-17 ◽  
Author(s):  
Minori Shinya ◽  
Cathrin Eschbach ◽  
Matthew Clark ◽  
Hans Lehrach ◽  
Makoto Furutani-Seiki
Keyword(s):  
Wnt Signaling ◽  
Neural Plate ◽  
Prechordal Plate ◽  
Anterior Neural Plate

Complex expression of the zp-50 pou gene in the embryonic zebrafish brain is altered by overexpression of sonic hedgehog

Development ◽  
1996 ◽  
Vol 122 (6) ◽  
pp. 1769-1780 ◽  
Author(s):  
G. Hauptmann ◽  
T. Gerster
Keyword(s):  
Sonic Hedgehog ◽  
Similar Response ◽  
Intercellular Signaling ◽  
Class Iii ◽  
Dorsoventral Patterning ◽  
Gene Encoding ◽  
Pou Domain ◽  
Distinct Cell ◽  
The Central Nervous System

We report the characterization of the zebrafish zp-50 class III POU domain gene. This gene is first activated in the prospective diencephalon after the end of the gastrula period. During somitogenesis, zp-50 is expressed in a very dynamic and complex fashion in all major subdivisions of the central nervous system. After one day of development, zp-50 transcripts are present in the fore- and midbrain in several distinct cell clusters. In the hindbrain, zp-50 expression is found in two types of domains. Correct zp-50 expression in the ventral fore- and midbrain requires genes known to be involved in dorsoventral patterning of the zebrafish CNS. Transcripts of the sonic hedgehog (shh) gene encoding an intercellular signaling molecule are detected in the forming diencephalon shortly prior to the appearance of zp-50 mRNA. Correct expression in this region of both shh, and zp-50, requires a functional cyclops (cyc) locus: shh and zp-50 transcripts are likewise absent from the ventral rostral brain of mutant cyc−/− embryos. Injection of synthetic shh mRNA into fertilized eggs causes ectopic zp-50 expression at more dorsal positions of the embryonic brain. The close spatial and temporal coincidence of expression in the rostral brain, the similar response to the cyc- mutation, and the ectopic zp-50 expression in the injection experiments all suggest that zp-50 may directly respond to the reception of the Shh signal.

scholarly journals An enigmatic translocation of the vertebrate primordial eye field

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
R. G. Loosemore ◽  
S. D. Matthaei ◽  
T. C. Stanger
Keyword(s):  
Progenitor Cells ◽  
Neural Plate ◽  
Evolutionary Significance ◽  
Mapping Data ◽  
Retinal Progenitor ◽  
Vertebrate Embryo ◽  
Eye Field ◽  
Optic Vesicles ◽  
Contralateral Eye ◽  
Anterior Neural Plate

Abstract The primordial eye field of the vertebrate embryo is a single entity of retinal progenitor cells spanning the anterior neural plate before bifurcating to form bilateral optic vesicles. Here we review fate mapping data from zebrafish suggesting that prior to evagination of the optic vesicles the eye field may undergo a Maypole-plait migration of progenitor cells through the midline influenced by the anteriorly subducting diencephalon. Such an enigmatic translocation of scaffolding progenitors could have evolutionary significance if pointing, by way of homology, to an ancient mechanism for transition of the single eye field in chordates to contralateral eye fields in vertebrates.

Early subdivisions in the neural plate define distinct competence for inductive signals

Development ◽  
2002 ◽  
Vol 129 (1) ◽  
pp. 83-93 ◽  
Author(s):  
Daisuke Kobayashi ◽  
Makoto Kobayashi ◽  
Ken Matsumoto ◽  
Toshihiko Ogura ◽  
Masato Nakafuku ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Optic Tectum ◽  
Neural Plate ◽  
Specific Response ◽  
Embryonic Brain ◽  
Fgf Receptor ◽  
Fibroblast Growth Factor 8 ◽  
Equivalent Potential ◽  
The Brain ◽  
Anterior Posterior

Regionalization of the embryonic brain is achieved through multi-step processes that operate sequentially and/or simultaneously. Localized sources of various signaling molecules act as organizing centers that pattern neighboring fields to create molecularly distinct domains. We investigated the mechanisms underlying the regionally distinct competence for two such organizing signals, Fibroblast growth factor 8 (Fgf8) and Sonic hedgehog (Shh), using chick embryos. First, we demonstrated that FGF receptor 1 (Fgfr1) and Fgfr3, expressed differentially in the developing brain, possess an equivalent potential to induce the regionally distinct Fgf8-responsive genes, depending on the anterior-posterior dimension of the brain. Next we found that homeodomain transcription factors Six3 and Irx3 can alter the regional responses to both Fgf8 and Shh in the forebrain. Six3 confers the ability to express Bf1, a gene essential for the telencephalon and eye development, and Nkx2.1, which is required for development of the hypothalamus. In contrast, Irx3 confers the ability to express En2 and Nkx6.1 in response to Fgf8 and Shh, respectively. Furthermore, an alteration in the region-specific response to Fgf8 upon misexpression of Irx3 resulted in transformation of diencephalic and possibly telencephalic tissues into the optic tectum. Finally, we demonstrated that Six3 and Irx3 can mutually repress their expression, which may contribute to the establishment of their complementary expression domains in the neural plate. These repressive interactions are specific, as Six3 did not repress Gbx2, and Irx3 did not disturb Otx2 expression. These findings provide evidence that the early embryonic forebrain is demarcated into two domains with distinct genetic programs, which argues against the authentic telen-diencephalic subdivision.

A Xenopus homebox gene defines dorsal-ventral domains in the developing brain

Development ◽  
1993 ◽  
Vol 118 (1) ◽  
pp. 193-202 ◽  
Author(s):  
M.S. Saha ◽  
R.B. Michel ◽  
K.M. Gulding ◽  
R.M. Grainger
Keyword(s):  
Initial Step ◽  
Neural Plate ◽  
Developing Brain ◽  
Vertebrate Development ◽  
Tissue Interactions ◽  
Temporal Localization ◽  
Distinguishing Features ◽  
The Brain ◽  
Anterior Neural Plate ◽  
Anterior Posterior

One of the distinguishing features of vertebrate development is the elaboration of the anterior neural plate into forebrain and midbrain, yet little is known about the early tissue interactions that regulate pattern formation in this region or the genes that mediate these interactions. As an initial step toward analyzing the process of regionalization in the anterior-most region of the brain, we have screened an anterior neural cDNA library for homeobox clones and have identified one which we have called XeNK-2 (Xenopus NK-2) because of its homology to the NK-2 family of homeobox genes. From neurula stages, when XeNK-2 is first detectable, through hatching stages, XeNK-2 mRNA is expressed primarily in the anterior region of the brain. By swimming tadpole stages, XeNK-2 expression resolves into a set of bands positioned at the forebrain-midbrain and the midbrain-hindbrain boundaries, after which XeNK-2 transcripts are no longer detectable. In addition to localized expression along the anterior-posterior axis, XeNK-2 may also play a role in the process of regionalization along the dorsal-ventral axis of the developing brain. At all stages examined, XeNK-2 mRNA is restricted to a pair of stripes that are bilaterally symmetrical in the ventral-lateral region of the brain. To begin to identify the tissue interactions that are required for the proper spatial and temporal localization of XeNK-2, we have performed a series of explant experiments. Consistent with earlier work showing that the A/P axis is not fixed at mid-gastrula stages, we show that XeNK-2 expression is activated when assayed in gastrula stage explants taken from any region along the entire A/P axis and that the tissue interactions necessary to localize XeNK-2 along the A/P axis are not completed until later neurula stages.

Ace/Fgf8 is required for forebrain commissure formation and patterning of the telencephalon

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2549-2561 ◽  
Author(s):  
S. Shanmugalingam ◽  
C. Houart ◽  
A. Picker ◽  
F. Reifers ◽  
R. Macdonald ◽  
...  
Keyword(s):  
Fibroblast Growth Factors ◽  
Large Family ◽  
Neural Tissue ◽  
Neural Plate ◽  
Normal Morphology ◽  
The Central Nervous System ◽  
Ace Activity ◽  
Midline Cells ◽  
Inductive Activity ◽  
Anterior Neural Plate

Fibroblast growth factors (Fgfs) form a large family of secreted signalling proteins that have a wide variety of roles during embryonic development. Within the central nervous system (CNS) Fgf8 is implicated in patterning neural tissue adjacent to the midbrain-hindbrain boundary. However, the roles of Fgfs in CNS tissue rostral to the midbrain are less clear. Here we examine the patterning of the forebrain in zebrafish embryos that lack functional Fgf8/Ace. We find that Ace is required for the development of midline structures in the forebrain. In the absence of Ace activity, midline cells fail to adopt their normal morphology and exhibit altered patterns of gene expression. This disruption to midline tissue leads to severe commissural axon pathway defects, including misprojections from the eye to ectopic ipsilateral and contralateral targets. Ace is also required for the differentiation of the basal telencephalon and several populations of putative telencephalic neurons but not for overall regional patterning of forebrain derivatives. Finally, we show that ace expression co-localises with anterior neural plate cells that have previously been shown to have forebrain patterning activity. Removal of these cells leads to a failure in induction of ace expression indicating that loss of Ace activity may contribute to the phenotypes observed when anterior neural plate cells are ablated. However, as ace mutant neural plate cells still retain at least some inductive activity, then other signals must also be produced by the anterior margin of the neural plate.

scholarly journals The surface-anchored NanA protein promotes pneumococcal brain endothelial cell invasion

2009 ◽  
Vol 206 (9) ◽  
pp. 1845-1852 ◽  
Author(s):  
Satoshi Uchiyama ◽  
Aaron F. Carlin ◽  
Arya Khosravi ◽  
Shannon Weiman ◽  
Anirban Banerjee ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Critical Role ◽  
Host Cells ◽  
Attributable Mortality ◽  
Infection Model ◽  
Gene Encoding ◽  
Neurological Sequelae ◽  
Sialidase Activity ◽  
The Central Nervous System ◽  
Necessary And Sufficient

In humans, Streptococcus pneumoniae (SPN) is the leading cause of bacterial meningitis, a disease with high attributable mortality and frequent permanent neurological sequelae. The molecular mechanisms underlying the central nervous system tropism of SPN are incompletely understood, but include a primary interaction of the pathogen with the blood–brain barrier (BBB) endothelium. All SPN strains possess a gene encoding the surface-anchored sialidase (neuraminidase) NanA, which cleaves sialic acid on host cells and proteins. Here, we use an isogenic SPN NanA-deficient mutant and heterologous expression of the protein to show that NanA is both necessary and sufficient to promote SPN adherence to and invasion of human brain microvascular endothelial cells (hBMECs). NanA-mediated hBMEC invasion depends only partially on sialidase activity, whereas the N-terminal lectinlike domain of the protein plays a critical role. NanA promotes SPN–BBB interaction in a murine infection model, identifying the protein as proximal mediator of CNS entry by the pathogen.

Sign in / Sign up

Export Citation Format

Share Document