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At least 1,171 records · Page 65Linked to original sources
PubMed1998

A small population of anterior cells patterns the forebrain during zebrafish gastrulation.

During gastrulation in vertebrates, dorsal ectoderm is induced to form neural tissue that later gives rise to the brain and spinal cord. This induction depends on signals arising from a group of cells on the dorsal side of the gastrula. This group of cells constitutes the organizer. It is thought that the organizer initially induces neural tissue with anterior, or forebrain, character, and that other signals subsequently posteriorize neural tissue in the trunk. Here we show that development of the anterior central nervous system of the zebrafish embryo also depends on a small group of ectodermal cells located in the prospective head region. Removal of these ectodermal cells during gastrulation perturbs subsequent neural patterning and results in widespread cell death. Transplantation of these cells shows that they can induce forebrain-specific gene expression in more posterior regions of the neural plate. Our results indicate that an early step in neural patterning is the establishment of a small population of signalling cells within the most anterior region of the embryo. These cells are required for patterning and survival of the anterior brain.

Animals↗
PubMed2000

Synergistic effects of FGF and non-ridge ectoderm on gene expression involved in the formation of the anteroposterior axis of the chick limb bud in cell culture.

Skeletal patterning of the vertebrate limb is controlled by the zone of polarizing activity (ZPA), apical ectodermal ridge (AER) and dorsal ectoderm. In the present study, to understand the involvement of fibroblast growth factor (FGF) and non-ridge ectoderm in anteroposterior (AP) axis formation, gene expression in chick limb bud mesenchymal cells in culture was investigated by reverse transcription-polymerase chain reaction and in situ hybridization. It was found that Shh expression was locally maintained in the mesenchymal cells underneath and near non-ridge ectoderm in coculture with the posterior mesenchymal cells and non-ridge ectoderm in the presence of FGF-4 by in situ hybridization. In Shh-expressing anterior limb bud mesenchymal cells cultured with non-ridge ectoderm, it was also discovered that Bmp-2 was activated in the presence of FGF-2, -4 and -8, while Hoxd-13 was activated in the presence of FGF-4 and that FGF-2 had a similar effect but FGF-8 did not. This result indicates that Hoxd-13 activation by SHH depends on non-ridge ectoderm and FGF-2 or FGF-4, and that there may be a difference in the effect on AP axis formation of the limb bud between FGF-2, -4 and -8. Possible roles of these genes and signal molecules in AP pattern formation are discussed.

Animals↗
PubMed2004

Pax6 interacts with cVax and Tbx5 to establish the dorsoventral boundary of the developing eye.

Dorsoventral pattern formation of the optic cup is essential for vertebrate eye morphogenesis and retinotectal topographic mapping. Dorsal and ventral aspects of the eye are distinct at early stages of development; cVax homeodomain protein expression is confined to the ventral optic cup, whereas Tbx5 (T-box transcription factor) expression domain becomes restricted to the dorsal region. Misexpression of cVax or Tbx5 induces profound defects in eye morphology and abnormal visual projections. In the Pax6-/- mutant Tbx5 fails to be expressed, and Vax1 and -2 are abnormally present in the entire optic vesicle. During eye development Pax6 becomes expressed in a gradient at the optic cup stage due to the specific activation of a highly conserved intronic alpha enhancer in the Pax6 locus. We observed that the highest level of Pax6 in the optic cup corresponds to the boundary between non-overlapping cVax and Tbx5 territories. To further investigate how these transcription factors control the patterning of the eye, we overexpressed Pax6 in the chick optic cup (E2) using in ovo electroporation. We observed that overexpression of Pax6 extends the Tbx5 and Bmp4 domains but reduces the cVax expression domains in the E3 chick eye. This results in an abnormal eye phenotype at E4. In addition, we showed that cVax and Tbx5 interact with Pax6 and modulate in an opposite manner the activity of the Pax6 alpha enhancer. Moreover, the Pax6/cVax interaction inhibits the transactivation properties of Pax6. These results demonstrate that Pax6 together with cVax and Tbx5 mediate dorsoventral patterning of the eye.

Animals↗
PubMed2001

Generating patterns from fields of cells. Examples from Drosophila segmentation.

In Drosophila, a cascade of maternal, gap, pair-rule and segment polarity genes subdivides the antero/posterior axis of the embryo into repeating segmental stripes. This review summarizes what happens next, i.e. how an intrasegmental pattern is generated and controls the differentiation of specific cell types in the epidermis. Within each segment, cells secreting the signalling molecules Wingless (the homologue of vertebrate Wnt-1) and Hedgehog are found in narrow stripes on both sides of the parasegmental boundary. The Wingless and Hedgehog organizing activities help to establish two more stripes per segment that localize ligands for the Epidermal Growth Factor and the Notch signalling pathways, respectively. These four signals then act at short range and in concert to control epidermal differentiation at the single cell level across the segment. This example from Drosophila provides a paradigm for how organizers generate precise patterns, and ultimately different cell types, in a naïve field of cells.

Animals↗
PubMed1998

Relationship between standing posture and stability.

BACKGROUND AND PURPOSE: This study determined whether persons with stability impairments have postural aberrations. We investigated whole-body posture and its relationship to center-of-gravity (COG) stability. SUBJECTS: Data from 27 subjects with vestibular hypofunction and 26 subjects without vestibular impairment were analyzed. METHOD: An optoelectronic full-body system measured kinematics. Force plates measured ground reaction forces while subjects stood with their feet 30 cm apart and eyes open and with their feet together and eyes closed. RESULTS: The subjects with vestibular hypofunction demonstrated less stability than the subjects without impairment, but there were no postural differences. Subjects with vestibular hypofunction had more weight on the left lower extremity during standing with feet apart. In all subjects in both groups, during standing with feet apart, the COG was anterior to the ankle, knee, back, and shoulder and posterior to the hip and neck. Subjects had an anterior pelvic tilt, extended trunk and head, right laterally flexed trunk and pelvis, and flexed knees. With their feet together, subjects increased their anterior pelvic tilt; trunk, head, and knee flexion; and anterior COG position. CONCLUSION AND DISCUSSION: Posture and stability had a low correlation. Subjects with bilateral vestibular hypofunction did not demonstrate a forward head or backward trunk lean, as has been reported anecdotally. Changing from standing with feet apart to feet together increased whole-body movement patterns to control standing stability.

Adult↗
PubMed2006

Functional genomics of early cortex patterning.

Several lines of evidence have illuminated the fundamental developmental principles involved in establishing and implementing pattern formation in the mammalian neocortex. A recent study has sought to unravel the underlying genetic control of cortex patterning by elucidating the transcriptional profile of discrete neocortical regions.

Animals↗
PubMed2002

Early patterning of the mouse embryo--contributions of sperm and egg.

The first cleavage of the fertilised mouse egg divides the zygote into two cells that have a tendency to follow distinguishable fates. One divides first and contributes its progeny predominantly to the embryonic part of the blastocyst, while the other, later dividing cell, contributes mainly to the abembryonic part. We have previously observed that both the plane of this first cleavage and the subsequent order of blastomere division tend to correlate with the position of the fertilisation cone that forms after sperm entry. But does sperm entry contribute to assigning the distinguishable fates to the first two blastomeres or is their fate an intrinsic property of the egg itself? To answer this question we examined the distribution of the progeny of early blastomeres in embryos never penetrated by sperm - parthenogenetic embryos. In contrast to fertilised eggs, we found there is no tendency for the first two parthenogenetic blastomeres to follow different fates. This outcome is independent of whether parthenogenetic eggs are haploid or diploid. Also unlike fertilised eggs, the first 2-cell blastomere to divide in parthenogenetic embryo does not necessarily contribute more cells to the blastocyst. However, even when descendants of the first dividing blastomere do predominate, they show no strong predisposition to occupy the embryonic part. Thus blastomere fate does not appear to be decided by differential cell division alone. Finally, when the cortical cytoplasm at the site of sperm entry is removed, the first cleavage plane no longer tends to divide the embryo into embryonic and abembryonic parts. Together these results indicate that in normal development fertilisation contributes to setting up embryonic patterning, alongside the role of the egg.

Animals↗
PubMed2003

Unique and combinatorial functions of Fgf3 and Fgf8 during zebrafish forebrain development.

Complex spatiotemporal expression patterns of fgf3 and fgf8 within the developing zebrafish forebrain suggest their involvement in its regionalisation and early development. These factors have unique and combinatorial roles during development of more posterior brain regions, and here we report similar findings for the developing forebrain. We show that Fgf8 and Fgf3 regulate different aspects of telencephalic development, and that Fgf3 alone is required for the expression of several telencephalic markers. Within the diencephalon, Fgf3 and Fgf8 act synergistically to pattern the ventral thalamus, and are implicated in the regulation of optic stalk formation, whereas loss of Fgf3 alone results in defects in ZLI development. Forebrain commissure formation was abnormal in the absence of either Fgf3 or Fgf8; however, most severe defects were observed in the absence of both. Defects were observed in patterning of both the midline territory, within which the commissures normally form, and neuronal populations, whose axons comprise the commissures. Analysis of embryos treated with an FGFR inhibitor suggests that continuous FGF signalling is required from gastrulation stages for normal forebrain patterning, and identifies additional requirements for FGFR activity.

Animals↗
PubMed2006

Sfrp1 and Sfrp2 regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis.

Regulation of Wnt signaling is essential for embryonic patterning. Sfrps are secreted Wnt antagonists that directly interact with the Wnt ligand to inhibit signaling. Here, we show that Sfrp1 and Sfrp2 are required for anteroposterior (AP) axis elongation and somitogenesis in the thoracic region during mouse embryogenesis. Double homozygous mutations in Sfrp1 and Sfrp2 lead to severe shortening of the thoracic region. By contrast, a homozygous mutation in one or the other exerts no effect on embryogenesis, indicating that Sfrp1 and Sfrp2 are functionally redundant. The defect of a shortened thoracic region appears to be the consequence of AP axis reduction and incomplete somite segmentation. The reduction in the AP axis is partially due to abnormalities in cell migration of pre-somitic mesoderm from the end of gastrulation. Aberrant somite segmentation is associated with altered oscillations of Notch signaling, as evidenced by abnormal Lfng and Hes7 expression during somitogenesis in the thoracic region. This study suggests that Wnt regulation by Sfrp1 and Sfrp2 is required for embryonic patterning.

Animals↗
PubMed1998

Determination of the zebrafish forebrain: induction and patterning.

We report an analysis of forebrain determination and patterning in the zebrafish Danio rerio. In order to study these events, we isolated zebrafish homologs of two neural markers, odd-paired-like (opl), which encodes a zinc finger protein, and fkh5, which encodes a forkhead domain protein. At mid-gastrula, expression of these genes defines a very early pattern in the presumptive neurectoderm, with opl later expressed in the telencephalon, and fkh5 in the diencephalon and more posterior neurectoderm. Using in vitro explant assays, we show that forebrain induction has occurred even earlier, by the onset of gastrulation (shield stage). Signaling from the early gastrula shield, previously shown to be an organizing center, is sufficient for activation of opl expression in vitro. In order to determine whether the organizer is required for opl regulation, we removed from late blastula stage embryos either the presumptive prechordal plate, marked by goosecoid (gsc) expression, or the entire organizer, marked by chordin (chd) expression. opl was correctly expressed after removal of the presumptive prechordal plate and consistently, opl was correctly expressed in one-eyed pinhead (oep) mutant embryos, where the prechordal plate fails to form. However, after removal of the entire organizer, no opl expression was observed, indicating that this region is crucial for forebrain induction. We further show that continued organizer function is required for forebrain induction, since beads of BMP4, which promotes ventral fates, also prevented opl expression when implanted during gastrulation. Our data show that forebrain specification begins early during gastrulation, and that a wide area of dorsal mesendoderm is required for its patterning.

Amino Acid Sequence↗
PubMed1999

The Drosophila dead ringer gene is required for early embryonic patterning through regulation of argos and buttonhead expression.

The dead ringer (dri) gene of Drosophila melanogaster is a member of the recently discovered ARID-box family of eukaryotic genes that encode proteins with a conserved DNA binding domain. dri itself is highly conserved, with specific orthologs in the human, mouse, zebrafish and C. elegans genomes. We have generated dri mutant alleles to show that dri is essential for anterior-posterior patterning and for muscle development in the embryo. Consistent with the mutant phenotype and the sequence-specific DNA-binding properties of its product, dri was found to be essential for the normal early embryonic expression pattern of several key regulatory genes. In dri mutant embryos, expression of argos in the terminal domains was severely reduced, accounting for the dri mutant head phenotype. Conversely, buttonhead expression was found to be deregulated in the trunk region, accounting for the appearance of ectopic cephalic furrows. Curiously, dri was found also to be required for maintenance of expression of the ventrolateral region of even-skipped stripe four. This study establishes dri as an essential co-factor in the regulated expression of specific patterning genes during early embryogenesis.

Animals↗
PubMed2000

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

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.

Animals↗
PubMed2000

Windbeutel is required for function and correct subcellular localization of the Drosophila patterning protein Pipe.

Drosophila embryonic dorsal-ventral polarity originates in the ovarian follicle through the restriction of pipe gene expression to a ventral subpopulation of follicle cells. Pipe, a homolog of vertebrate glycosaminoglycan-modifying enzymes, directs the ventral activation of an extracellular serine proteolytic cascade which defines the ventral side of the embryo. When pipe is expressed uniformly in the follicle cell layer, a strong ventralization of the resulting embryos is observed. Here, we show that this ventralization is dependent on the other members of the dorsal group of genes controlling dorsal-ventral polarity, but not on the state of the Epidermal Growth Factor Receptor signal transduction pathway which defines egg chamber polarity. Pipe protein expressed in vertebrate tissue culture cells localizes to the endoplasmic reticulum. Strikingly, coexpression of the dorsal group gene windbeutel in those cells directs Pipe to the Golgi. Similarly, Pipe protein exhibits an altered subcellular localization in the follicle cells of females mutant for windbeutel. Thus, Windbeutel protein enables the correct subcellular distribution of Pipe to facilitate its pattern-forming activity.

Animals↗
PubMed2002

FGF3 and FGF8 mediate a rhombomere 4 signaling activity in the zebrafish hindbrain.

The segmentation of the vertebrate hindbrain into rhombomeres is highly conserved, but how early hindbrain patterning is established is not well understood. We show that rhombomere 4 (r4) functions as an early-differentiating signaling center in the zebrafish hindbrain. Time-lapse analyses of zebrafish hindbrain development show that r4 forms first and hindbrain neuronal differentiation occurs first in r4. Two signaling molecules, FGF3 and FGF8, which are both expressed early in r4, are together required for the development of rhombomeres adjacent to r4, particularly r5 and r6. Transplantation of r4 cells can induce expression of r5/r6 markers, as can misexpression of either FGF3 or FGF8. Genetic mosaic analyses also support a role for FGF signaling acting from r4. Taken together, our findings demonstrate a crucial role for FGF-mediated inter-rhombomere signaling in promoting early hindbrain patterning and underscore the significance of organizing centers in patterning the vertebrate neural plate.

Animals↗
PubMed2000

Vertebrate orthologues of the Drosophila region-specific patterning gene teashirt.

In Drosophila the teashirt gene, coding for a zinc finger protein, is active in specific body parts for patterning. For example, Teashirt is required in the trunk (thorax and abdomen) tagmata of the embryo, parts of the intestine and the proximal parts of appendages. Here we report the isolation of vertebrate cDNAs related to teashirt. As in Drosophila, human and murine proteins possess three widely spaced zinc finger motifs. Additionally, we describe the expression patterns of the two murine genes. Both genes show regionalized patterns of expression, in the trunk, in the developing limbs and the gut.

Amino Acid Sequence↗