Genes involved in forebrain development in the zebrafish, Danio rerio

Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 191-203 ◽  
Author(s):  
C.P. Heisenberg ◽  
M. Brand ◽  
Y.J. Jiang ◽  
R.M. Warga ◽  
D. Beuchle ◽  
...  

We identified four zebrafish mutants with defects in forebrain induction and patterning during embryogenesis. The four mutants define three genes: masterblind (mbl), silberblick (slb), and knollnase (kas). In mbl embryos, the anterior forebrain acquires posterior forebrain characteristics: anterior structures such as the eyes, olfactory placodes and the telencephalon are missing, whereas the epiphysis located in the posterior forebrain is expanded. In slb embryos, the extension of the embryonic axis is initially delayed and eventually followed by a partial fusion of the eyes. Finally, in kas embryos, separation of the telencephalic primordia is incomplete and dorsal midline cells fail to form a differentiated roof plate. Analysis of the mutant phenotypes indicates that we have identified genes essential for the specification of the anterior forebrain (mbl), positioning of the eyes (slb) and differentiation of the roof plate (kas). In an appendix to this study we list mutants showing alterations in the size of the eyes and abnormal differentiation of the lenses.

2021 ◽  
Vol 7 (24) ◽  
pp. eabg5968
Author(s):  
Baruch Haimson ◽  
Oren Meir ◽  
Reut Sudakevitz-Merzbach ◽  
Gerard Elberg ◽  
Samantha Friedrich ◽  
...  

Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here, we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression and is missing in galliforms. The morphology and wiring at brachial levels of the chicken embryonic spinal cord resemble those of ephrin-B3 null mice. Dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.


Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 983-991 ◽  
Author(s):  
Astrid Vogel-Höpker ◽  
Hermann Rohrer

The role of BMPs in the development of the major noradrenergic centre of the brain, the locus coeruleus (LC), was investigated. LC generation is reflected by initial expression of the transcription factors Phox2a and Phox2b in dorsal rhombomere1 (r1), followed by expression of dopamine-β-hydroxylase and tyrosine hydroxylase. Bmp5 is expressed in the dorsal neuroepithelium in proximity to Phox2-expressing cells. BMP inhibition in stage 10 chick embryos resulted in the lack of LC neurones or in their generation at the dorsal midline, and loss of roof plate and rhombic lip, but it did not affect neural crest development. These results reveal late essential BMP functions in the specification of dorsal neuronal phenotypes in r1, including LC neurones, and in the development of dorsal midline structures.


Development ◽  
1995 ◽  
Vol 121 (8) ◽  
pp. 2595-2609 ◽  
Author(s):  
K. Woo ◽  
S.E. Fraser

The zebrafish is an excellent vertebrate model for the study of the cellular interactions underlying the patterning and the morphogenesis of the nervous system. Here, we report regional fate maps of the zebrafish anterior nervous system at two key stages of neural development: the beginning (6 hours) and the end (10 hours) of gastrulation. Early in gastrulation, we find that the presumptive neurectoderm displays a predictable organization that reflects the future anteroposterior and dorsoventral order of the central nervous system. The precursors of the major brain subdivisions (forebrain, midbrain, hindbrain, neural retina) occupy discernible, though overlapping, domains within the dorsal blastoderm at 6 hours. As gastrulation proceeds, these domains are rearranged such that the basic order of the neural tube is evident at 10 hours. Furthermore, the anteroposterior and dorsoventral order of the progenitors is refined and becomes aligned with the primary axes of the embryo. Time-lapse video microscopy shows that the rearrangement of blastoderm cells during gastrulation is highly ordered. Cells near the dorsal midline at 6 hours, primarily forebrain progenitors, display anterior-directed migration. Cells more laterally positioned, corresponding to midbrain and hindbrain progenitors, converge at the midline prior to anteriorward migration. These results demonstrate a predictable order in the presumptive neurectoderm, suggesting that patterning interactions may be well underway by early gastrulation. The fate maps provide the basis for further analyses of the specification, induction and patterning of the anterior nervous system, as well as for the interpretation of mutant phenotypes and gene-expression patterns.


Development ◽  
1994 ◽  
Vol 120 (8) ◽  
pp. 2225-2234 ◽  
Author(s):  
K. Shimamura ◽  
S. Hirano ◽  
A.P. McMahon ◽  
M. Takeichi

E-cadherin is transiently expressed in local regions of the embryonic mouse brain, which include several patchy areas on the mesencephalon and diencephalon and their roof plate and part of cerebellar rudiments. In the present study, we compared this E-cadherin expression with that of Wnt-1, which occurs in specific zones in the embryonic brain, and found certain spatiotemporal relations between them: Wnt-1 expression tended to run parallel or overlap with peripheries of the E-cadherin-positive areas. For example, in the dorsal midline, Wnt-1 was expressed at the middle of the roof plate, while E-cadherin was absent in the middle zone but detected in two arrays of marginal roof plate cells. Furthermore, alpha N-catenin, a cadherin-associated protein, was found to occur at the roof plate of the mesencephalon and diencephalon, coinciding with Wnt-1 expression. The expression of these molecules was then studied in two alleles of the Wnt-1 mutation, Wnt-1sw and Wnt-1neo. In mice homozygous for these mutant genes, E-cadherin expression in the roof plate was up-regulated; the middle E-cadherin-negative zone disappeared. Moreover, E-cadherin expression in the roof plate began earlier in the mutant mice than in wild-type mice. On the contrary, alpha N-catenin expression in the dorsal midline was suppressed in these mutants. These changes in cadherin and catenin expression occurred at the level of mRNA expression. These results suggest that the Wnt-1 signal is, either directly or indirectly, involved in the regulation of expression of E-cadherin and alpha N-catenin in restricted regions of the embryonic brain. This mechanism may contribute to the patterning of the expression of these adhesion-related proteins in the embryonic brain.


Development ◽  
1995 ◽  
Vol 121 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
M.C. Danos ◽  
H.J. Yost

The left-right body axis is defined relative to the dorsal-ventral and anterior-posterior body axes. Since left-right asymmetries are not randomly oriented with respect to dorsal-ventral and anterior-posterior spatial patterns, it is possible that a common mechanism determines all three axes in a coordinate manner. Two approaches were undertaken to determine whether alteration in dorsal-anterior development perturbs the left-right orientation of heart looping. Treatments known to decrease dorsal-anterior development in Xenopus laevis, UV irradiation during the first cell cycle or Xwnt-8 DNA injections into dorsal blastomeres, caused an increase in cardiac left-right reversals. The frequency of left-right reversal was correlated with the severity of dorsal-anterior perturbation and with the extent of anterior notochord regression. Injection of Xwnt-8 DNA into dorsal midline cells resulted in decreased dorsal-anterior development and a correlated increase in cardiac left-right reversals. In contrast, injection of Xwnt-8 DNA into cardiac progenitor blastomeres did not result in left-right reversals, and dorsal-anterior development and notochord formation were normal. Disrupting development of dorsal-anterior cells, including cells that give rise to the Organizer region and the notochord, results in the randomization of cardiac left-right asymmetry. These results suggest dorsal-anterior development and the regulation of left-right orientation are linked.


Development ◽  
1996 ◽  
Vol 123 (1) ◽  
pp. 1-36 ◽  
Author(s):  
P. Haffter ◽  
M. Granato ◽  
M. Brand ◽  
M.C. Mullins ◽  
M. Hammerschmidt ◽  
...  

In a large-scale screen, we isolated mutants displaying a specific visible phenotype in embryos or early larvae of the zebrafish, Danio rerio. Males were mutagenized with ethylnitrosourea (ENU) and F2 families of single pair matings between sibling F1 fish, heterozygous for a mutagenized genome, were raised. Egg lays were obtained from several crosses between F2 siblings, resulting in scoring of 3857 mutagenized genomes. F3 progeny were scored at the second, third and sixth day of development, using a stereomicroscope. In a subsequent screen, fixed embryos were analyzed for correct retinotectal projection. A total of 4264 mutants were identified. Two thirds of the mutants displaying rather general abnormalities were eventually discarded. We kept and characterized 1163 mutants. In complementation crosses performed between mutants with similar phenotypes, 894 mutants have been assigned to 372 genes. The average allele frequency is 2.4. We identified genes involved in early development, notochord, brain, spinal cord, somites, muscles, heart, circulation, blood, skin, fin, eye, otic vesicle, jaw and branchial arches, pigment pattern, pigment formation, gut, liver, motility and touch response. Our collection contains alleles of almost all previously described zebrafish mutants. From the allele frequencies and other considerations we estimate that the 372 genes defined by the mutants probably represent more than half of all genes that could have been discovered using the criteria of our screen. Here we give an overview of the spectrum of mutant phenotypes obtained, and discuss the limits and the potentials of a genetic saturation screen in the zebrafish.


Development ◽  
1999 ◽  
Vol 126 (16) ◽  
pp. 3561-3571 ◽  
Author(s):  
T. Theil ◽  
G. Alvarez-Bolado ◽  
A. Walter ◽  
U. Ruther

Dentate gyrus and hippocampus as centers for spatial learning, memory and emotional behaviour have been the focus of much interest in recent years. The molecular information on its development, however, has been relatively poor. To date, only Emx genes were known to be required for dorsal telencephalon development. Here, we report on forebrain development in the extra toes (Xt(J)) mouse mutant which carries a null mutation of the Gli3 gene. This defect leads to a failure to establish the dorsal di-telencephalic junction and finally results in a severe size reduction of the neocortex. In addition, Xt(J)/Xt(J) mice show absence of the hippocampus (Ammon's horn plus dentate gyrus) and the choroid plexus in the lateral ventricle. The medial wall of the telencephalon, which gives rise to these structures, fails to invaginate during embryonic development. On a molecular level, disruption of dorsal telencephalon development in Xt(J)/Xt(J) embryos correlates with a loss of Emx1 and Emx2 expression. Furthermore, the expression of Fgf8 and Bmp4 in the dorsal midline of the telencephalon is altered. However, expression of Shh, which is negatively regulated by Gli3 in the spinal cord, is not affected in the Xt(J)/Xt(J) forebrain. This study therefore implicates Gli3 as a key regulator for the development of the dorsal telencephalon and implies Gli3 to be upstream of Emx genes in a genetic cascade controlling dorsal telencephalic development.


Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4366-4375 ◽  
Author(s):  
Yvonne A. R. White ◽  
Joshua T. Kyle ◽  
Antony W. Wood

Abstract IGF-II is the predominant IGF ligand regulating prenatal growth in all vertebrates, including humans, but its central role in placental development has confounded efforts to fully elucidate its functions within the embryo. Here we use a nonplacental model vertebrate (zebrafish) to interrogate the intraembryonic functions of IGF-II signaling. The zebrafish genome contains two coorthologs of mammalian IGF2 (igf2a, igf2b), which exhibit distinct patterns of expression during embryogenesis. Expression of igf2a mRNA is restricted to the notochord, primarily during segmentation/neurulation. By contrast, igf2b mRNA is expressed in midline tissues adjacent to the notochord, with additional sites of expression in the ventral forebrain, and the pronephros. To identify their intraembryonic functions, we suppressed the expression of each gene with morpholino oligonucleotides. Knockdown of igf2a led to defects in dorsal midline development, characterized by delayed segmentation, notochord undulations, and ventral curvature. Similarly, suppression of igf2b led to defects in dorsal midline development but also induced ectopic fusion of the nephron primordia, and defects in ventral forebrain development. Subsequent onset of severe body edema in igf2b, but not igf2a morphants, further suggested a distinct role for igf2b in development of the embryonic kidney. Simultaneous knockdown of both genes increased the severity of dorsal midline defects, confirming a conserved role for both genes in dorsal midline development. Collectively, these data provide evidence that the zebrafish orthologs of IGF2 function in dorsal midline development during segmentation/neurulation, whereas one paralog, igf2b, has evolved additional, distinct functions during subsequent organogenesis.


Neuroreport ◽  
1995 ◽  
Vol 6 (2) ◽  
pp. 281-283 ◽  
Author(s):  
Keiko Takiguchi-Hayashi ◽  
Yasuyoshi Arimatsu

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