scholarly journals Visceral endoderm-restricted translation of Otx1 mediates recovery of Otx2 requirements for specification of anterior neural plate and normal gastrulation

Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 5091-5104 ◽  
Author(s):  
D. Acampora ◽  
V. Avantaggiato ◽  
F. Tuorto ◽  
P. Briata ◽  
G. Corte ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Expression Patterns ◽  
Epileptic Seizures ◽  
Primitive Streak ◽  
Neural Plate ◽  
Visceral Endoderm ◽  
Temporal Expression ◽  
Biochemical Activity ◽  
The Difference ◽  
Anterior Neural Plate

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, contribute to brain morphogenesis. In particular Otx1 null mice are viable and show spontaneous epileptic seizures and abnormalities affecting the dorsal telencephalic cortex. Otx2 null mice die early in development and fail in specification of the rostral neuroectoderm and proper gastrulation. In order to determine whether Otx1(−/−)and Otx2(−/−) highly divergent phenotypes reflect differences in temporal expression or biochemical activity of OTX1 and OTX2 proteins, the Otx2-coding sequence was replaced by a human Otx1 full-coding cDNA. Homozygous mutant embryos recovered anterior neural plate and proper gastrulation but failed to maintain forebrain-midbrain identities, displaying a headless phenotype from 9 days post coitum (d.p.c.) onwards. Unexpectedly, in spite of the RNA distribution in both visceral endoderm (VE) and epiblast, the hOTX1 protein was synthesized only in the VE. This VE-restricted translation was sufficient to recover Otx2 requirements for specification of the anterior neural plate and proper organization of the primitive streak, thus providing evidence that the difference between Otx1 and Otx2 null mice phenotypes originates from their divergent expression patterns. Moreover, our data lead us to hypothesize that the differential post-transcriptional control existing between VE and epiblast cells may potentially contribute to fundamental regulatory mechanisms required for head specification.

scholarly journals Initiation of Murine Embryonic Erythropoiesis: A Spatial Analysis

Blood ◽  
1997 ◽  
Vol 89 (4) ◽  
pp. 1154-1164 ◽  
Author(s):  
Louise Silver ◽  
James Palis
Keyword(s):  
Expression Patterns ◽  
Erythroid Differentiation ◽  
Primitive Streak ◽  
Neural Plate ◽  
Temporal Expression ◽  
Targeted Disruption ◽  
Mesoderm Cell ◽  
Temporal And Spatial ◽  
Extraembryonic Mesoderm

Abstract Hematopoiesis in the mouse conceptus begins in the visceral yolk (VYS), with primitive erythroblasts first evident in blood islands at the headfold stage (E8.0). VYS erythropoiesis is decreased or abrogated by targeted disruption of the hematopoietic transcription factors tal-1, rbtn2, GATA-1, and GATA-2. To better understand the potential roles of these genes, and to trace the initial temporal and spatial development of mammalian embryonic hematopoiesis, we examined their expression patterns, and that of βH1-globin, in normal mouse conceptuses by means of in situ hybridization. Attention was focused on the 36-hour period from mid-primitive streak to early somite stages (E7.25 to E8.5), when the conceptus undergoes rapid morphologic changes with formation of the yolk sac and blood islands. Each of these genes was expressed in extraembryonic mesoderm, from which blood islands are derived. This VYS expression occurred in a defined temporal sequence: tal-1 and rbtn2 transcripts were detected earlier than the others, followed by GATA-2 and GATA-1, and then by βH1-globin. Transcripts for all of these genes were present in VYS mesoderm cell masses at the neural plate stage (E7.5), indicating commitment of these cells to the erythroid lineage before the appearance of morphologically recognizable erythroblasts. By early somite stages (E8.5), GATA-2 mRNA expression is downregulated in VYS blood islands as terminal primitive erythroid differentiation proceeds. We conclude that primitive mammalian erythropoiesis arises during gastrulation through the ordered temporal expression of tal-1, rbtn2, GATA2, and GATA-1 in a subset of extraembryonic mesoderm cells. During the stages analyzed, tal-1 and rbtn2 expression was also present in posterior embryonic mesoderm, while GATA-1 and GATA-2 expression was evident in extraembryonic tissues of ectodermal origin.

scholarly journals Anterior neural plate regionalization in cripto null mutant mouse embryos in the absence of node and primitive streak

2003 ◽  
Vol 264 (2) ◽  
pp. 537-549 ◽  
Author(s):  
Giovanna L Liguori ◽  
Diego Echevarría ◽  
Raffaele Improta ◽  
Massimo Signore ◽  
Eileen Adamson ◽  
...  
Keyword(s):  
Mutant Mouse ◽  
Primitive Streak ◽  
Neural Plate ◽  
Mouse Embryos ◽  
Null Mutant ◽  
Mutant Mouse Embryos ◽  
Anterior Neural Plate ◽  
Null Mutant Mouse

scholarly journals Multiple roles for FGF-3 during cranial neural development in the chicken

Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1399-1410 ◽  
Author(s):  
R. Mahmood ◽  
P. Kiefer ◽  
S. Guthrie ◽  
C. Dickson ◽  
I. Mason
Keyword(s):  
Neural Development ◽  
Primitive Streak ◽  
Neural Plate ◽  
Multiple Roles ◽  
Posterior Half ◽  
Temporal Expression ◽  
Pharyngeal Arches ◽  
Early Organogenesis ◽  
Vertebrate Embryos ◽  
Associated Function

FGF-3 has been implicated in the development of the hindbrain and otocyst in vertebrate embryos. Since the chicken embryo offers a favourable system in which to study the development of these structures, we have isolated and characterised cDNAs for chicken Fgf-3 and determined its pattern of expression in chick embryos from stage 3 (primitive streak) to stage 25 (early organogenesis). Within the developing cranial neural tube, Fgf-3 exhibits dynamic spatial and temporal expression. During extension of the head process, RNA is detected in the midline of the developing neural plate. In neurulating embryos, transcripts are observed initially in rhombomeres 4 and 5 of the hindbrain and later, in rhombomere 6. During hindbrain development, expression is lost from these rhombomeres, but becomes restricted to rhombomere boundaries, providing an intracellular marker which distinguishes a population of cells within boundary regions. Fgf-3 expression is elevated in ventral and medial boundary regions and is greatly reduced in dorsal parts. Studies of regenerating rhombomere boundaries show that Fgf-3 expression is induced in reforming boundaries when even-numbered rhombomere tissue is grafted next to odd, but not when like is juxtaposed to like. Fgf-3 disappears from boundary regions just prior to the loss of the morphological boundaries suggesting a boundary-associated function. Other sites of expression have also been identified. At early stages of development Fgf-3 is expressed in the epiblast and mesendoderm of the primitive streak, in mesoderm lateral to the streak and in Hensen's node. In older embryos transcripts are detected in the endoderm of the pharyngeal pouches, the ectoderm of the second and third pharyngeal arches and the stomodeum. Expression was also detected in the segmental plate and in the posterior half of the three most-recently generated somites.

Head induction in the chick by primitive endoderm of mammalian, but not avian origin

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 815-825 ◽  
Author(s):  
H. Knoetgen ◽  
C. Viebahn ◽  
M. Kessel
Keyword(s):  
Lower Layer ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Neural Plate ◽  
Visceral Endoderm ◽  
Avian Origin ◽  
Bmp Antagonist ◽  
Rabbit Embryos ◽  
Inductive Potential ◽  
Anterior Visceral Endoderm

Different types of endoderm, including primitive, definitive and mesendoderm, play a role in the induction and patterning of the vertebrate head. We have studied the formation of the anterior neural plate in chick embryos using the homeobox gene GANF as a marker. GANF is first expressed after mesendoderm ingression from Hensen's node. We found that, after transplantation, neither the avian hypoblast nor the anterior definitive endoderm is capable of GANF induction, whereas the mesendoderm (young head process, prechordal plate) exhibits a strong inductive potential. GANF induction cannot be separated from the formation of a proper neural plate, which requires an intact lower layer and the presence of the prechordal mesendoderm. It is inhibited by BMP4 and promoted by the presence of the BMP antagonist Noggin. In order to investigate the inductive potential of the mammalian visceral endoderm, we used rabbit embryos which, in contrast to mouse embryos, allow the morphological recognition of the prospective anterior pole in the living, pre-primitive-streak embryo. The anterior visceral endoderm from such rabbit embryos induced neuralization and independent, ectopic GANF expression domains in the area pellucida or the area opaca of chick hosts. Thus, the signals for head induction reside in the anterior visceral endoderm of mammals whereas, in birds and amphibia, they reside in the prechordal mesendoderm, indicating a heterochronic shift of the head inductive capacity during the evolution of mammalia.

Forebrain and midbrain development requires epiblast-restrictedOtx2translational control mediated by its 3′ UTR

Development ◽  
2001 ◽  
Vol 128 (15) ◽  
pp. 2989-3000 ◽  
Author(s):  
Pietro Pilo Boyl ◽  
Massimo Signore ◽  
Dario Acampora ◽  
Juan Pedro Martinez-Barbera ◽  
Cristina Ilengo ◽  
...  
Keyword(s):  
Brain Development ◽  
Translational Control ◽  
Transcriptional Control ◽  
Molecular Level ◽  
Regulatory Element ◽  
Untranslated Regions ◽  
Visceral Endoderm ◽  
Protein Levels ◽  
Neuronal Progenitor ◽  
Anterior Neural Plate

Otx genes play an important role in brain development. Previous mouse models suggested that the untranslated regions (UTRs) of Otx2 mRNA may contain regulatory element(s) required for its post-transcriptional control in epiblast and neuroectoderm. In order to study this, we have perturbed the 3′ UTR of Otx2 by inserting a small fragment of DNA from the λ phage. Otx2λ mutants exhibited proper gastrulation and normal patterning of the early anterior neural plate, but from 8.5 days post coitum they developed severe forebrain and midbrain abnormalities. OTX2 protein levels in Otx2λ mutants were heavily reduced in the epiblast, axial mesendoderm and anterior neuroectoderm but not in the visceral endoderm. At the molecular level, we found out that the ability of the Otx2λ mRNA to form efficient polyribosome complexes was impaired. Sequence analysis of the Otx2-3′ UTR revealed a 140 bp long element that is present only in vertebrate Otx2 genes and conserved in identity by over 80%. Our data provide experimental evidence that murine brain development requires accurate translational control of Otx2 mRNA in epiblast and neuronal progenitor cells. This leads us to hypothesise that this control might have important evolutionary implications.

scholarly journals Cables2 Is a Novel Smad2-Regulatory Factor Essential for Early Embryonic Development in Mice

2019 ◽  
Author(s):  
Tra Thi Huong Dinh ◽  
Hiroyoshi Iseki ◽  
Seiya Mizuno ◽  
Saori Iijima-Mizuno ◽  
Yoko Tanimoto ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Expression Patterns ◽  
Physiological Role ◽  
Primitive Streak ◽  
Early Embryonic Development ◽  
Visceral Endoderm ◽  
Tetraploid Complementation ◽  
Mouse Tissues

ABSTRACTCDK5 and Abl enzyme substrate 2 (Cables2), a member of the Cables family that has a C-terminal cyclin box-like domain, is widely expressed in adult mouse tissues. However, the physiological role of Cables2 in vivo is unknown. We show here that Cables2-deficiency causes post-gastrulation embryonic lethality in mice. The mutant embryos progress to gastrulation, but then arrest, and fail to grow. Analysis of gene expression patterns reveals that formation of the anterior visceral endoderm and the primitive streak is impaired in Cables2-deficient embryos. Tetraploid complementation analyses support the critical requirement of Cables2 in both the epiblast and visceral endoderm for progression of embryogenesis. In addition, we show that Cables2 physically interacts with a key mediator of the canonical Nodal pathway, Smad2, and augments its transcriptional activity. These findings provide novel insights into the essential role of Cables2 in the early embryonic development in mice.

Sequential roles for Otx2 in visceral endoderm and neuroectoderm for forebrain and midbrain induction and specification

Development ◽  
1998 ◽  
Vol 125 (5) ◽  
pp. 845-856 ◽  
Author(s):  
M. Rhinn ◽  
A. Dierich ◽  
W. Shawlot ◽  
R.R. Behringer ◽  
M. Le Meur ◽  
...  
Keyword(s):  
Es Cells ◽  
Homeobox Gene ◽  
Neural Plate ◽  
Regulatory Genes ◽  
Neural Function ◽  
Visceral Endoderm ◽  
Essential Function ◽  
The Brain ◽  
Anterior Neural Plate ◽  
Recombination Assay

The homeobox gene Otx2 is a mouse cognate of the Drosophila orthodenticle gene, which is required for development of the brain, rostral to rhombomere three. We have investigated the mechanisms involved in this neural function and specifically the requirement for Otx2 in the visceral endoderm and the neuroectoderm using chimeric analysis in mice and explant recombination assay. Analyses of chimeric embryos composed of more than 90% of Otx2−/− ES cells identified an essential function for Otx2 in the visceral endoderm for induction of the forebrain and midbrain. The chimeric studies also demonstrated that an anterior neural plate can form without expressing Otx2. However, in the absence of Otx2, expression of important regulatory genes, such as Hesx1/Rpx, Six3, Pax2, Wnt1 and En, fail to be initiated or maintained in the neural plate. Using explant-recombination assay, we could further demonstrate that Otx2 is required in the neuroectodem for expression of En. Altogether, these results demonstrate that Otx2 is first required in the visceral endoderm for the induction, and subsequently in the neuroectoderm for the specification of forebrain and midbrain territories.

Differential transcriptional control as the major molecular event in generating Otx1−/− and Otx2−/− divergent phenotypes

Development ◽  
1999 ◽  
Vol 126 (7) ◽  
pp. 1417-1426 ◽  
Author(s):  
D. Acampora ◽  
V. Avantaggiato ◽  
F. Tuorto ◽  
P. Barone ◽  
M. Perera ◽  
...  
Keyword(s):  
Amino Acid ◽  
Inner Ear ◽  
Transcriptional Control ◽  
Expression Patterns ◽  
Sequence Divergence ◽  
Epileptic Seizures ◽  
Amino Acid Sequences ◽  
Functional Homology ◽  
Multiple Abnormalities ◽  
Temporal Profiles

Otx1 and Otx2, two murine homologs of the Drosophila orthodenticle (otd) gene, show a limited amino acid sequence divergence. Their embryonic expression patterns overlap in spatial and temporal profiles with two major exceptions: until 8 days post coitum (d.p.c.) only Otx2 is expressed in gastrulating embryos, and from 11 d.p.c. onwards only Otx1 is transcribed within the dorsal telencephalon. Otx1 null mice exhibit spontaneous epileptic seizures and multiple abnormalities affecting primarily the dorsal telencephalic cortex and components of the acoustic and visual sense organs. Otx2 null mice show heavy gastrulation abnormalities and lack the rostral neuroectoderm corresponding to the forebrain, midbrain and rostral hindbrain. In order to define whether these contrasting phenotypes reflect differences in expression pattern or coding sequence of Otx1 and Otx2 genes, we replaced Otx1 with a human Otx2 (hOtx2) full-coding cDNA. Interestingly, homozygous mutant mice (hOtx2(1)/hOtx2(1)) fully rescued epilepsy and corticogenesis abnormalities and showed a significant improvement of mesencephalon, cerebellum, eye and lachrymal gland defects. In contrast, the lateral semicircular canal of the inner ear was never recovered, strongly supporting an Otx1-specific requirement for the specification of this structure. These data indicate an extended functional homology between OTX1 and OTX2 proteins and provide evidence that, with the exception of the inner ear, in Otx1 and Otx2 null mice contrasting phenotypes stem from differences in expression patterns rather than in amino acid sequences.

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.

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