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A Ruiz i Altaba

Publications and source records attributed to A Ruiz i Altaba.

At least 37 records · Page 2Linked to original sources

Involvement of Livertine, a hepatocyte growth factor family member, in neural morphogenesis.

The formulation of the nervous system in vertebrate embryos involves extensive morphogenetic movements that include the folding of the neural tube and the migration of neural crest cells. Changes in cell shape and cell movements underlie neural morphogenesis but the molecular mechanisms involved in these processes in vivo are not well understood. Here, we show that a new member of the hepatocyte growth factor family, which we name Livertine, is expressed in frog embryos in neural cells including neural crest and midline neural plate cells which are undergoing pronounced morphogenetic movements. The ectopic expression of Livertine perturbs gastrulation and leads to positional changes in injected cells without apparently changing cell type. These results suggest that one of the normal functions of Livertine is the control of neural morphogenesis in the vertebrate embryo.

Amino Acid Sequence↗

Coexpression of HNF-3 beta and Isl-1/2 and mixed distribution of ventral cell types in the early neural tube.

Pattern formation in the vertebrate ventral neural tube has been proposed to depend on the ability of notochord-derived signals to induce the differentiation of distinct cell types in a distance-dependent manner. To determine whether the distribution of early differentiating cell types in the ventral neural tube is consistent with the operation of such a mechanism in vivo, the early localization of Isl-1/2+ motor neurons in relation to HNF-3 beta+ floor plate cells has been investigated. In the most immature regions of the caudal spinal cord of early rat and chick embryos, an initial mixed distribution of cell types was detected that develops into a distribution characteristic of the final embryonic pattern where different cell types are found at distinct locations. In addition, a number of cells that coexpress both markers are detected within the floor plate. At later stages, coexpression is also detected in the hindbrain in the boundary region between HNF-3 beta+ ventricular cells and Isl-1/2+ motor neurons. The mixed distribution of early differentiating cells expressing HNF-3 beta and Isl-1/2 and the coexpression of these markers in single cells within the floor plate suggest that secondary cellular interactions are important in the generation of the final embryonic pattern of the neural tube.

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Early stages of notochord and floor plate development in the chick embryo defined by normal and induced expression of HNF-3 beta.

We have cloned a cDNA encoding the chick HNF-3 beta gene and have used RNA and antibody probes that detect HNF-3 beta to monitor the normal and induced expression of the gene in early embryos. HNF-3 beta expressed in Koller's sickle, at the onset of primitive streak formation, and later in Hensen's node. At neural plate and neural tube stages, HNF-3 beta is expressed transiently in the notochord and is then expressed by floor plate cells. Prospective floor plate cells that are located in the epiblast immediately anterior to Hensen's node prior to its regression do not express HNF-3 beta, providing evidence that floor plate fate is normally determined only after these cells populate the midline of the neural plate and overlie the notochord. Removal of the notochord in vivo prevents floor plate development and in this condition HNF-3 beta is not expressed by cells at the ventral midline of the neural tube. Notochord grafts induce ectopic floor plate development and ectopic neural expression of HNF-3 beta. In vitro, neural plate explants are induced to express HNF-3 beta by notochord cells in a contact-dependent but cycloheximide-resistant manner, providing evidence that expression of HNF-3 beta is a direct response of neural plate cells to notochord-derived inducing signals.

Amino Acid Sequence↗

Restrictions to floor plate induction by hedgehog and winged-helix genes in the neural tube of frog embryos.

Intercellular signaling molecules of the vertebrate hedgehog family and transcription factors of the winged-helix family have been implicated in floor plate development. We have examined the consequences of misexpressing the vertebrate hedgehog gene vhh-1 (sonic hedgehog, shh) and the winged-helix gene HNF-3 beta in the neural plate and neural tube of frog embryos. Misexpression of either of these genes induces floor plate differentiation at ectopic locations. However, ectopic floor plate induction in response to both vhh-1 and HNF-3 beta was temporally and spatially restricted. At neural plate stages, ectopic floor plate differentiation was not detected. After neural tube closure, ectopic floor plate differentiation was detected but was restricted predominantly to the dorsal region of the neural tube. The ability of winged-helix and vertebrate hedgehog genes to induce floor plate differentiation in vivo may, therefore, be constrained by additional signals that specify the time and position of floor plate differentiation.

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The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo.

HNF-3 beta, a transcription factor of the winged-helix family, is expressed in embryonic and adult endoderm and also in midline cells of the node, notochord, and floor plate in mouse embryos. To define the function of HNF-3 beta, a targeted mutation in the HNF-3 beta locus was generated by homologous recombination in embryonic stem cells. Mice lacking HNF-3 beta die by embryonic day (E) 10-11. Mutant embryos examined from E6.5 to E9.5 do not form a distinct node and lack a notochord. In addition, mutant embryos show marked defects in the organization of somites and neural tube that may result from the absence of the notochord. The neural tube of mutant embryos exhibits overt anteroposterior polarity but lacks a floor plate and motor neurons. Endodermal cells are present but fail to form a gut tube in mutant embryos. These studies indicate that HNF-3 beta has an essential role in the development of axial mesoderm in mouse embryos.

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Floor plate and motor neuron induction by vhh-1, a vertebrate homolog of hedgehog expressed by the notochord.

The differentiation of distinct cell types in the ventral neural tube depends on local inductive signals from the notochord. We have isolated a vertebrate homolog of the Drosophila segment polarity gene hedgehog (hh) from zebrafish and rat, termed vhh-1. vhh-1 is expressed in the node, notochord, floor plate, and posterior limb bud mesenchyme. Each of these cell groups has floor plate inducing activity, suggesting that the vhh-1 gene may encode a floor plate-inducing molecule. Widespread expression of rat vhh-1 in frog embryos leads to ectopic floor plate differentiation in the neural tube. In vitro tests for the signaling functions of vhh-1 demonstrate that COS cells expressing the rat vhh-1 gene induce floor plate and motor neuron differentiation in neural plate explants. vhh-1 may, therefore, contribute to the floor plate and motor neuron inducing activities of the notochord.

Amino Acid Sequence↗

Pattern formation in the vertebrate neural plate.

Recent advances have been made in the understanding of the cellular and molecular mechanisms involved in the formation and patterning of the neural plate of vertebrate embryos. Both planar and vertical signaling pathways appear to be involved in the neural induction and axial patterning of the neural plate. The neural plate, behaving as a developmental field, might be patterned by signals emanating from boundary regions: the organizer region and the midline and edges of the neural plate. Here, A. Ruiz i Altaba describes a possible model for anteroposterior patterning involving ;lanar signals for amphibian, avian and mammalian embryos, compares the axial patterning of the neural plate with the patterning of insect epithelia, and discussed possible roles of noggin, follistatin and hedgehog-related genes in neural induction and patterning.

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Ectopic neural expression of a floor plate marker in frog embryos injected with the midline transcription factor Pintallavis.

The floor plate, a cell group that develops at the midline of the neural plate in response to inductive signals from the notochord, has been implicated in the control of dorsoventral neural pattern. The frog Pintallavis gene, encoding a member of the HNF-3/fork head transcription factor family, is expressed in the notochord and in midline neural plate cells that give rise to the floor plate. To examine whether Pintallavis might be involved in regulating the differentiation of the floor plate, we ectopically expressed Pintallavis by injection of synthetic mRNA into two-cell frog embryos. Injection of Pintallavis mRNA resulted in the ectopic expression of F-spondin, a gene encoding a floor plate-specific adhesion molecule, at the dorsal midline of the neural tube. The expression of Pintallavis in midline cells may therefore contribute to the establishment of the floor plate fate.

Albinism↗

Induction and axial patterning of the neural plate: planar and vertical signals.

In this review I summarize recent findings on the contributions of different cell groups to the formation of the basic plan of the nervous system of vertebrate embryos. Midline cells of the mesoderm--the organizer, notochord, and prechordal plate--and midline cells of the neural ectoderm--the notoplate and floor plate--appear to have a fundamental role in the induction and patterning of the neural plate. Vertical signals acting across tissue layers and planar signals acting through the neural epithelium have distinct roles and cooperate in induction and pattern formation. Whereas the prechordal plate and notochord have distinct vertical signaling properties, the initial anteroposterior (A-P) pattern of the neural plate may be induced by planar signals originating from the organizer region. Planar signals from the notoplate may also contribute to the mediolateral (M-L) patterning of the neural plate. These and other findings suggest a general view of neural induction and axial patterning.

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Sequential expression of HNF-3 beta and HNF-3 alpha by embryonic organizing centers: the dorsal lip/node, notochord and floor plate.

Axial patterning in the nervous system of vertebrate embryos depends on inductive signals that derive from the organizer region (the dorsal lip in amphibians and the node in birds and mammals) and leter from the notochord and floor plate. Previous studies have shown that Pintallavis, a member of the HNF-3/fork head transcription factor family, is expressed selectively by these cell groups in frog embryos and may be involved in regulating neural development. We report here that in early rat and mouse embryos, the embryonic endoderm, the node, the notochord and the floor plate express two related transcription factors, HNF-3 alpha and HNF-3 beta, which also function in the control of liver cell differentiation. Early embryonic tissues express variant forms of HNF-3 beta which derive from the use of 5' alternative exons. Within the organizer region and notochord, HNF-3 beta and HNF-3 alpha have distinct temporal patterns of expression and appear in partially overlapping domains. The early expression pattern of mammalian HNF-3 beta in the node, notochord and midline neural plate cells is similar to that of Pintallavis in frog embryos. There does not appear to be a Pintallavis homologue in mice. This prompted us to isolate and analyze the expression of the frog HNF-3 beta gene. In frog embryos, HNF-3 beta is expressed in the dorsal lip, pharyngeal endoderm and floor plate. In contrast to mammalian HNF-3 beta, the onset of frog HNF-3 beta expression in neural tissue occurs after neural tube closure. Thus, the combined expression patterns of Pintallavis and HNF-3 beta in frogs is equivalent to that of HNF-3 beta in rats and mice. Within neural tissue, the onset of expression of these regulatory genes define successive stages in the differentiation of floor plate cells. The results reported here show that closely related members of the HNF-3/fork head gene family are expressed by axial midline cell groups involved in neural induction and patterning and suggest the involvement of these genes in the development of the vertebrate neuraxis.

Amino Acid Sequence↗

Midline cells and the organization of the vertebrate neuraxis.

Vertebrate embryos exhibit a striking midline axis of symmetry that can be recognized in the overall body plan, the framework of skeletal structures and the organization of the nervous system. Cells located at the midline of the embryo during gastrulation have a crucial influence on the establishment of cell identity and pattern within the nervous system. The identification of transcription factors and secreted proteins that are expressed by these midline cell groups has begun to provide a molecular characterization of the organizing centers that establish early neural identity and pattern.

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Planar and vertical signals in the induction and patterning of the Xenopus nervous system.

The cellular mechanisms responsible for the formation of the Xenopus nervous system have been examined in total exogastrula embryos in which the axial mesoderm appears to remain segregated from prospective neural ectoderm and in recombinates of ectoderm and mesoderm. Posterior neural tissue displaying anteroposterior pattern develops in exogastrula ectoderm. This effect may be mediated by planar signals that occur in the absence of underlying mesoderm. The formation of a posterior neural tube may depend on the notoplate, a midline ectodermal cell group which extends along the anteroposterior axis. The induction of neural structures characteristic of the forebrain and of cell types normally found in the ventral region of the posterior neural tube requires additional vertical signals from underlying axial mesoderm. Thus, the formation of the embryonic Xenopus nervous system appears to involve the cooperation of distinct planar and vertical signals derived from midline cell groups.

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Pintallavis, a gene expressed in the organizer and midline cells of frog embryos: involvement in the development of the neural axis.

We have identified a novel frog gene, Pintallavis (the Catalan for lipstick), that is related to the fly fork head and rat HNF-3 genes. Pintallavis is expressed in the organizer region of gastrula embryos as a direct zygotic response to dorsal mesodermal induction. Subsequently, Pintallavis is expressed in axial midline cells of all three germ layers. In axial mesoderm expression is graded with highest levels posteriorly. Midline neural plate cells that give rise to the floor plate transiently express Pintallavis, apparently in response to induction by the notochord. Overexpression of Pintallavis perturbs the development of the neural axis, suppressing the differentiation of anterior and dorsal neural cell types but causing an expansion of the posterior neural tube. Our results suggest that Pintallavis functions in the induction and patterning of the neural axis.

Amino Acid Sequence↗

Retinoic acid modifies mesodermal patterning in early Xenopus embryos.

Treatment of early Xenopus embryos with retinoic acid (RA) produces a concentration-dependent series of defects in anterior axial structures that range from small deletions to embryos lacking heads. The graded series of axial defects obtained after RA administration to early embryos appears to result, in part, from actions of RA on embryonic mesoderm. RA modifies the differentiation of anterior dorsal mesoderm from animal cap ectoderm induced by mesoderm-inducing peptide growth factors (PGFs). Concentrations of RA that suppress anterior dorsal mesoderm result in the differentiation of mesoderm of more posterior or ventral character. The suppression of anterior dorsal mesoderm may account for the absence of anterior neural ectoderm after RA treatment. Although RA changes the character of mesoderm, it does not seem to affect mesodermal induction by PGFs or the levels of Xhox3 mRNA induced in the mesoderm by PGFs. RA therefore appears to affect steps downstream from those involved in the initial induction of mesoderm. In experiments to examine the possible physiological role of RA in early Xenopus development, dorsal and ventral ectoderm were found to respond differently to identical concentrations of PGFs. One potential basis for this heterogeneity is the existence of a localized inhibitor, possibly RA, in the early Xenopus embryo. RA could therefore contribute to axial patterning by inhibiting the development of mesoderm of different character induced by PGFs.

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Retinoic acid modifies the pattern of cell differentiation in the central nervous system of neurula stage Xenopus embryos.

Neural cell markers have been used to examine the effect of retinoic acid (RA) on the development of the central nervous system (CNS) of Xenopus embryos. RA treatment of neurula stage embryos resulted in a concentration-dependent perturbation of anterior CNS development leading to a reduction in the size of the forebrain, midbrain and hindbrain. In addition the overt segmental organization of the hindbrain was abolished by high concentrations of RA. The regional expression of two cell-specific markers, the homeobox protein Xhox3 and the neurotransmitter serotonin was also examined in embryos exposed to RA. Treatment with RA caused a concentration-dependent change in the pattern of expression of Xhox3 and serotonin and resulted in the ectopic appearance of immunoreactive neurons in anterior regions of the CNS, including the forebrain. Collectively, our results extend previous studies by showing that RA treatment of embryos at the neurula stage inhibits the development of anterior regions of the CNS while promoting the differentiation of more posterior cell types. The relevance of these findings to the possible role of endogenous retinoids in the determination of neural cell fate and axial patterning is discussed.

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Axial patterning and the establishment of polarity in the frog embryo.

We review the early development of the frog Xenopus laevis, concentrating on events that lead to the establishment of the body plan. Recent molecular and embryological experiments suggest that peptide growth factors and homeobox genes interact to specify cell fates and pattern during early development of this vertebrate.

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