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At least 865 records · Page 48Linked to original sources
PubMed1993

Retinal afferents innervate functionally tectal but not neocortical grafts placed in lesioned superior colliculus of adult rats.

Solid pieces of tectum or occipital neocortex derived from 17-day rat fetuses were placed over the lesioned right superior colliculus (SC) in adult rats as sheets retaining the internal structure of the embryonal tissue. The upper laminae of the recipient's SC (approximately up to stratum opticum) were removed by aspiration after the neocortex overlying the SC was aspirated out. Two to 5 months after the operation a microelectrode study of the neuronal electrical activity in the grafts was performed. Recordings from the tectal transplants revealed normal patterns of the spontaneous neuronal activity in all grafts and clear neuronal reactions to visual stimuli in a large portion of them (6 out of 11). Visual reactions in these grafts were recorded from the majority of studied neurons (185/226). The properties of the receptive fields as well as the range of latencies of the reactions corresponded to those characteristic of the normal SC. Topographic representation of the visual field upon the transplants was found. Recordings from the cortical grafts showed an abnormal character of the spontaneous neuronal activity and the absence of reactions to any sensory stimulation of the recipients. The data obtained suggest that regenerating optic axons in adult hosts retain specificity in functional innervation of only appropriate target neurons and can re-establish the topographic representation of the retina upon tectal grafts. Retinal afferents innervate functionally tectal but not neocortical grafts placed in lesioned superior colliculus of adult rats.

Animals↗
PubMed1988

Developmental genetics of the gastrulation defective locus in Drosophila melanogaster.

The fs(1)gastrulation defective (dg) locus is one of the dorsal-group genes of Drosophila. Maternal expression of this gene is required for gastrulation movements and the differentiation of structures along the embryonic dorso-ventral axis. Twelve alleles of gd displayed a complex pattern of complementation, suggesting a direct interaction between subunits of a multimeric protein. Essential expression of the gd locus was strictly maternal with no zygotic contribution by the paternally derived allele. Clonal analysis revealed that expression of the gd locus was required in the germ line and that extreme dorsalization represented the null gd phenotype. Temperature-sensitive (ts) alleles displayed a ts period that included the last 4-5 hr of oogenesis and the first 1.5-2 hr of embryogenesis. Eggs from one ts allelic combination displayed reduced hatching when retained in the ovary at permissive temperatures, suggesting the loss of a labile egg component. This lability may also be responsible for the variable phenotypes displayed by offspring from individual females.

Alleles↗
PubMed1990

Structure and developmental expression of the chicken NGF receptor.

The nucleotide and deduced amino acid sequence of a cDNA clone of the chicken NGF receptor (NGFR) is reported and is compared with sequences of mammalian NGF receptors. A model is presented in which monodentate or bidentate binding of NGF dimers to repeated cysteine-rich sequence elements of the receptor yields low- or high-affinity NGF binding, respectively. In situ hybridization is used to characterize expression of NGFR in developing chick from 40 hr to 10 days of embryogenesis. NGFR mRNA expression is detected in premigratory neural crest cells, in epibranchial placode cells, and in all sensory, sympathetic and parasympathetic derivatives of these structures. In the embryonic CNS, NGFR mRNA is detected in the mantle zone but not the periventricular germinal zone throughout most of the neural tube. By Embryonic Day 8, NGFR mRNA is detected in a substantial fraction of cells in every brain region, with highest levels present in developing motor neurons. NGFR mRNA also is transiently expressed in many mesenchymal cell populations including cells in branchial arch, sclerotome, muscle anlagen, and feather follicles. The functional significance of wide-spread embryonic expression of the NGF receptor is discussed.

Amino Acid Sequence↗
PubMed1984

Cloning and transcriptional analysis of the segmentation gene fushi tarazu of Drosophila.

In the course of studying the Antennapedia (Antp) locus, we found that one of the 3' Antp exons has weak cross-homology to another gene affecting segmentation, fushi tarazu (ftz; meaning "not enough segments"), which is 30 kb to the left of Antp. Homozygous ftz- embryos die before hatching and lack alternate body segments. The reduced number of segments results from the fusion of the anterior portion of one segment with the posterior portion of the next segment. The ftz gene encodes a single 1.9 kb poly(A)+ RNA expressed exclusively from the early blastoderm to gastrula stages of embryonic development. The structure of the ftz gene has been analyzed by S1 nuclease mapping and by restriction mapping of a cDNA clone. The ftz gene consists of two exons, and it is the 3' exon that cross-hybridizes with the 3' exon of Antp. The role of ftz in cell determination is discussed.

Animals↗
PubMed1995

Analysis of the genes involved in organizing the tail segments of the Drosophila melanogaster embryo.

The metameric organization of the Drosophila melanogaster tail is obscured by developmental events that partially suppress or fuse some of its regions. To better define the developmental origins and segmental identities in the tail of the Drosophila embryo, we documented expression patterns and mutant phenotypes of several genes that play important roles in its morphogenesis. We documented the domains of engrailed (en), Abdominal-B (Abd-B) and caudal (cad) expression in the tail region. The staining pattern of cut (ct) was used to correlate the embryonic sense organs with their respective positions on the larval cuticle. The en patterns in different Bithorax-Complex (BX-C) Abd-B morphogenetic (m) and regulatory (r) mutants demonstrated that Abd-B functions to, among other things, suppress embryonic ventral epidermal structures on the posterior side of A8 to A9. Ventral epidermal structures were not added back into the en pattern in r- or BX-C- mutants, indicating that although the BX-C functions extend through A10, other non-BX-C genes must be required for development of this segment.

Animals↗
PubMed2006

Identification and developmental expression analysis of a novel homeobox gene closely linked to the mouse Twirler mutation.

The Twirler mutation arose spontaneously and causes inner ear defects in heterozygous and cleft lip and/or cleft palate in homozygous mutant mice, providing a unique animal model for investigating the molecular mechanisms of inner ear and craniofacial development. Here, we report the identification of a novel homeobox gene, Iroquois-related homeobox like-1 (Irxl1), from the Twirler locus. Irxl1 encodes a TALE-family homeodomain protein with its homeodomain exhibiting the highest amino acid sequence identity (54%) to those of invertebrate Iroquois and vertebrate Irx subfamily members. The putative Irxl1 protein lacks the Iro-box, a conserved motif in all known members of the Irx subfamily. Searching the databases showed that Irxl1 orthologs exist in Xenopus, chick, and mammals. In situ hybridization analyses of mouse embryos at various developmental stages showed that Irxl1 mRNA is highly expressed in the frontonasal process and palatal mesenchyme during primary and secondary palate development. In addition, Irxl1 mRNA is strongly expressed in mesenchyme surrounding the developing inner ear, in discrete regions of the developing mandible, in the dermamyotome during somite differentiation, and in a subset of muscular structures in late embryonic stages. The developmental expression pattern indicates that Irxl1 is a good candidate gene for the Twirler gene.

Amino Acid Sequence↗
PubMed2003

Sonic hedgehog regulates the position of the trigeminal ganglia.

The trigeminal ganglia differentiate in part from specialized ectodermal structures in the embryonic head termed the trigeminal placodes. However, the signals which govern the migration of trigeminal precursors and the final morphology of the ganglia are poorly defined. Here, we show that notochord or floor plate tissue can induce the formation of ectopic sensory ganglia adjacent to the developing dorsal mesencephalon. Neurons within these ganglia coexpress the transcription factors Brn3a and Islet, which together characterize primary sensory neurons throughout the developing embryo. The ectopic ganglia originate from Pax3-expressing regions of the surface ectoderm that normally contribute to the ophthalmic trigeminal (op5), and can only be induced at developmental stages during which op5 precursors are present in the mesencephalic region. The migration of trigeminal precursors is also blocked by a local source of recombinant Shh, while in mouse embryos lacking Shh, these cells continue to migrate until they fuse into a single ganglion at the ventral midline. Together, these results suggest that Shh acts to arrest the migration of sensory precursors rather than to induce sensory neurons de novo. Consistent with this hypothesis, Shh induces the expression of the proteoglycan PG-M/versican in the cranial mesoderm, which has been previously implicated in the regulation of the movement of sensory neural precursors.

Animals↗
PubMed2003

PCR-based quantification of amplified RNA from laser microdissected mouse liver samples.

New molecular methods such as quantitative reverse transcription-polymerase chain reaction (RT-PCR) and microarray gene expression analysis have been established recently to quantify gene expression in tissue samples. Such methods, although highly sensitive, require RNA quantities of at least several micrograms. These amounts are not available in many experiments concerning microdissected embryonic or regenerating structures. We combined laser-assisted tissue preparation, RNA amplification, and quantitative RT-PCR to estimate both accuracy and linearity of gene expression in small tissue samples. Our results show that mRNA isolated from laser-microdissected fetal liver tissue or regenerative nodules, which originated from EGFP-marked transplanted fetal cells, can be significantly increased with the amplification protocol. The quantitative expression ratio of the genes albumin and GAPDH was conserved after one and two rounds of amplification compared to nonamplified material. Furthermore, genes expressed at low levels such as the transcription factor C/EBPbeta become detectable after two rounds of amplification in small microdissected tissue samples.

Albumins↗
PubMed1997

Comparative effects of essential and nonessential metals on preimplantation mouse embryo development in vitro.

It is well recognized that deficiencies of essential trace elements during early development can result in structural abnormalities and/or embryonic death. Recently, there has been increasing interest in the concept that small excesses of essential metals can also have negative effects on the developing embryo. We hypothesized that, with respect to toxicity, metals with similar physico-chemical properties would act by similar mechanisms to influence the preimplantation embryo. In the current study we investigated the influence of four essential (Cu, Mn, Fe, Zn), and eight nonessential (Cr, Hg, Pb, V, Al, Ag, Cd, As) metals on mouse preimplantation embryonic development. Two cell stage mouse embryos were cultured for 72 h in media containing varying metal concentrations (0.05 - 200 microM). Embryo cell differentiation and proliferation were respectively assessed by scoring for blastocyst formation and final embryo cell number. Both nonessential and essential metals were embryotoxic at relatively low concentrations. However, in contrast to our expectations, at similar molar concentrations, redox active essential metals were less toxic than non-redox active nonessential metals. These data suggest that direct metal binding to critical membrane sites and/or intracellular ligands, including protein and nucleic acids, may trigger abnormal development and death prior to metal-associated oxidative damage.

Animals↗
PubMed1998

40-MHZ echocardiography scanner for cardiovascular assessment of mouse embryos.

Congenital heart disease results from genetic defects that are manifested at early stages of embryogenesis. The mouse is the preferred animal model for studies of mammalian embryonic development and for an increasing number of human disease models. A number of genes identified in the mouse are critical for normal cardiovascular development, but an understanding of the underlying mechanisms regulating heart development is still incomplete, in part because of the lack of methods to measure hemodynamics in live mouse embryos. We describe the development of a 40-MHz ultrasound scanner, which allows image-guided continuous-wave and pulsed Doppler blood flow measurements in mouse embryos, in utero, at the critical early developmental stages. Doppler waveforms acquired from mouse embryonic umbilical vessels, descending aorta, and cardiac ventricles are presented to demonstrate the utility of the method. By combining image-guided ultrasound Doppler with the many available mouse mutants, this approach should lead to new insights into embryonic cardiovascular structure-function relationships.

Animals↗
PubMed1996

Presynaptic development at the Drosophila neuromuscular junction: assembly and localization of presynaptic active zones.

We describe the extent to which presynaptic structures at the embryonic neuromuscular junction of Drosophila can form in mutants where development of postsynaptic somatic muscles is affected. Although twist mutant embryos lack mesoderm, motor axons still grow out of the CNS and form morphologically normal presynaptic active zones, independent of their target cells. In myoblast city mutant embryos, myoblasts do not fuse but form fully differentiated mononucleate muscles, which make functional neuromuscular synapses with correctly localized presynaptic active zones. Myoblasts also fail to fuse but still attract appropriate innervation in mef2 mutant embryos. However, these myoblasts fail to differentiate into muscles and presynaptic active zones fail to localize at neuromuscular contacts. Thus, the process of synapse formation can be genetically separated from the process of target recognition, revealing that localization of presynaptic active zones requires mef2-dependent muscle differentiation.

Animals↗
PubMed1998

Toward understanding SOX9 function in chondrocyte differentiation.

The transcription factors that trigger the determinative switch to chondrocyte differentiation in mesenchymal cells are still unknown. In humans, mutations in the gene for SOX9, a transcription factor with a DNA-binding domain similar to that of the mammalian testis-determining factor SRY, cause campomelic dysplasia, a severe dwarfism syndrome which affects all cartilage-derived structures. During mouse embryonic development, the Sox9 gene becomes active in all prechondrocytic mesenchymal condensations, and at later stages its expression is maintained at high levels in fully differentiated chondrocytes. A chondrocyte-specific enhancer in the gene for collagen type II (Col2a1), a characteristic marker of chondrocytes, is a direct target for SOX9, and ectopic expression of SOX9 in transgenic mouse embryos is sufficient to activate the endogenous Col2a1 gene in some tissues. These data suggest that SOX9 could have a major role in chondrogenesis. Studies are in progress to identify other target genes for SOX9 in chondrocytes and also other transcription factors that are believed to cooperate with SOX9 in the activation of chondrocyte-specific genes. Defining SOX9 function and the mechanisms that regulate SOX9 gene expression should contribute to a better understanding of chondrocyte differentiation.

Animals↗
PubMed2004

Early steps in the development of the forebrain.

The tremendous complexity of the adult forebrain makes it a challenging task to elucidate how this structure forms during embryonic development. Nevertheless, we are beginning to understand how a simple epithelial sheet of ectoderm gives rise to the labyrinthine network of cells that constitutes the functional forebrain. Here, we discuss early events in forebrain development--those that lead to the establishment of the anterior neural plate and the regional subdivision of this territory into the different domains of the prospective forebrain.

Animals↗
PubMed2005

Visualization of early embryos of the butterfly Bicyclus anynana.

We report on the first attempts, using both light and fluorescence microscopy, to visualize the developing embryo of the butterfly Bicyclus anynana. We developed a new protocol that enabled the clear visualization of the internal egg structures in early embryogenesis (1-24 h after egg laying). Dechorionation was followed by fixation and physical dissection of the external egg structures. Observations of embryonic and extra-embryonic cells were made using a Hoechst nuclear stain that fluoresces in the blue spectrum when bound to DNA and excited with ultraviolet (UV) light under a fluorescence microscope. Preliminary data on the developmental rate of the early embryo are also presented.

Animals↗
PubMed1993

The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma.

The tumour suppressor gene WT1 encodes a transcription factor expressed in tissues of the genito-urinary system. Inactivation of this gene is associated with the development of Wilms tumour a pediatric kidney cancer. We show that WT1 is also expressed at high levels in many supportive structures of mesodermal origin in the mouse. We also describe a case of adult human mesothelioma, a tumour derived from the peritoneal lining, that contains a homozygous point mutation within WT1. This mutation, within the putative transactivation domain, converts the protein from a transcriptional repressor of its target sequence to a transcriptional activator. The role of WT1 in normal development thus extends to diverse structures derived from embryonic mesoderm and disruption of WT1 function contributes to the onset of adult, as well as pediatric, tumours.

Adult↗
PubMed2002

The cancer connection: BRCA1 and BRCA2 tumor suppression in mice and humans.

BRCA1 and BRCA2 mutations are estimated to be responsible for the great majority of familial breast and ovarian cancers. Much progress has been made toward the understanding of the function of these proteins through genetic, biochemical, and structural studies. The embryonic lethality encountered in the knockout mouse initially hindered the development of mouse models aimed at studying tumor suppression. However, mice that harbor hypomorphic Brca1 and Brca2 alleles and cre-mediated tissue-specific deletions for Brca1 and Brca2 have been generated. Mice deficient for either Brca1 or Brca2 sustain a wide range of carcinoma and mammary epithelium deleted for Brca1 or Brca2 is highly susceptible to mammary tumorigenesis. Mammary (and other) tumors occur at long latency as compared to oncogene-induced mouse tumors. p53 deficiency is highly cooperative with both Brca1 and Brca2 in promoting tumorigenesis. Analysis of Brca1-associated mammary tumors reveals significant similarities to BRCA1-associated breast cancer in regard to high tumor grade, hormone receptor negativity, a high incidence of p53 mutations and genetic instability.

Animals↗
PubMed1998

Targeted disruption of ATF4 discloses its essential role in the formation of eye lens fibres.

BACKGROUND: Activating transcription factor-4 (ATF4)--also termed CREB2, C/ATF, and TAXREB67--is a basic-leucine zipper (bZip) transcription factor that belongs to the ATF/CREB family. In addition to its own family members, ATF4 can also form heterodimers with other related but distinct bZIP proteins such as the C/EBP, AP-1 and Maf families, which may give rise to a variety of combinatorial diversity in gene regulation. In order to assess the in vivo essential role of ATF4, we have generated mice lacking ATF4 by gene targeting. RESULTS: ATF4-deficient mice exhibited severe microphthalmia. Although ATF4-deficient eyes revealed a normal gross lens structure up to embryonic day 14.5, later on the ATF4-deficient lens, degenerated due to apoptosis without the formation of lens secondary fibre cells. Retinal development was normal in the mutant mice. The lens-specific expression of ATF4 in the mutant mice led not only to the recovery of lens secondary fibres but also to the induction of hyperplasia of these fibres. CONCLUSION: These results demonstrated that ATF4 is essential for the later stages of lens fibre cell differentiation.

Activating Transcription Factor 4↗
PubMed2002

Multi-field 3D scanning light microscopy of early embryogenesis.

A computer-controlled microscopy system was devised to allow the observation of avian embryo development over an extended time period. Parallel experiments, as well as extended specimen volumes, can be recorded at cellular resolution using a three-dimensional scanning procedure. The resulting large set of data is processed automatically into registered, focal- and positional-drift corrected mosaic images, assembled as montages of adjacent microscopic fields. The configuration of the incubator and a sterile embryo chamber prevents condensation of the humidified culturing atmosphere in the optical path and is compatible with both differential interference contrast and epifluorescence optics. As a demonstration, recordings are presented showing the large-scale remodelling of the embryonic primordial vascular structure.

Animals↗