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PubMed2006

The homeodomain transcription factor drg11 is expressed in primary sensory neurons and their putative CNS targets during embryonic development of the zebrafish.

The drg11 gene is a member of the vertebrate aristaless-related gene family and encodes a paired homeodomain transcription factor. Its expression is largely restricted to PNS neurons subserving somatosensory functions and their CNS targets in rodents. The phenotype of drg11 null mice suggests that it is crucial for the proper development in the embryo of nociceptive circuits. To allow functional studies in the zebrafish, a simple vertebrate model organism, we have cloned the homologous gene and studied its expression throughout embryonic development. drg11 transcripts are first detected at neurula stage in the developing trigeminal ganglion, where it persists throughout development. This is followed by transient expression in spinal cord mechanosensory Rohon-Beard neurons shortly before axogenesis. Expression is later evident in neuronal populations of the dorsal spinal cord and in the dorsal root ganglia. In the developing brain, drg11 expression is mainly restricted to sensory neuron populations of the midbrain and hindbrain, in cranial sensory ganglia and in the habenula. Unlike rodents, however, trochlear motor neurons transiently express drg11. Our results suggest that drg11 expression in the developing zebrafish is, in common with its mammalian homologous gene, predominantly localised to neurons in sensory processing areas of the embryonic nervous system and is both spatially and temporally regulated.

Amino Acid Sequence↗
PubMed2003

Knockout of ERK5 causes multiple defects in placental and embryonic development.

BACKGROUND: ERK5 is a member of the mitogen activated protein kinase family activated by certain mitogenic or stressful stimuli in cells, but whose physiological role is largely unclear. RESULTS: To help determine the function of ERK5 we have used gene targeting to inactivate this gene in mice. Here we report that ERK5 knockout mice die at approximately E10.5. In situ hybridisation for ERK5, and its upstream activator MKK5, showed strong expression in the head and trunk of the embryo at this stage of development. Between E9.5 and E10.5, multiple developmental problems are seen in the ERK5-/- embryos, including an increase in apoptosis in the cephalic mesenchyme tissue, abnormalities in the hind gut, as well as problems in vascular remodelling, cardiac development and placental defects. CONCLUSION: Erk5 is essential for early embryonic development, and is required for normal development of the vascular system and cell survival.

Abdomen↗
PubMed1975

Effects of increased partial pressures of oxygen on the embryonic and post-embryonic development of drosophila melanogaster.

The objective of this investigation was to study the effects of increased oxygen pressures on the development of Drosophila melanogaster. Oxygen is a potent inhibitor of embryonic and post-embryonic development of Drosophila. The lowest partial pressure of O2 (Po2) found to elicit measurable inhibitory effects on development is 0.6 ATA. Continuous exposure of developing Drosophila to 0.6 ATA O2 elicits primarily a larvicidal effect; surviving larvae exhibit delays in initial puparium formation and in mean day of adult eclosion: several resultant adults exhibit the effects of O2-induced teratogenesis in that body and wing abnormalities become manifest which do not breed true on matings and back crosses. Continuous exposure to 0.8 or 1.0 ATA O2 results in developmental arrest in the second larval instar followed by death. This development arrest is reversible depending upon the duration of exposure. As concerns lethality, early larval stages are more sensitive to O2 than late larval stages which, in turn, are more sensitive than early or late pupal stages: the embryo is the more resistant of the development stages. As concerns sensitivity for teratogenesis, the embryo is the most sensitive stage.

Animals↗
PubMed1999

p53 in embryonic development: maintaining a fine balance.

In addition to its role as a tumour suppressor and cell-cycle checkpoint control protein, p53 has been implicated as an important protein in embryonic development. Despite the viability of most p53 null mice, evidence has accumulated that p53 may regulate differentiation and the response of embryonic cells to diverse environmental stresses. Moreover, it appears that maintenance of a fine balance of p53 protein levels within embryonic cells is important for optimal development. Inappropriate overexpression or underexpression of p53 can lead to embryonic lethality or increased risk of malformations. The p53 protein may utilize multiple functional activities in its regulation of developmental processes.

Animals↗
PubMed1998

Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development.

The expression patterns of the three different peroxisome proliferator-activated receptor (PPAR) isotypes have been determined during rat embryonic development by in situ hybridization. The expression of PPARalpha starts late in development, with increasing levels in organs such as liver, kidney, intestine, and pancreas, in which it will also be present later in adulthood to regulate its specific target genes. PPARalpha is also transiently expressed in the embryonic epidermis and central nervous system. PPARgamma presents a very restricted pattern of expression, being strongly expressed in brown adipose tissue, in which differentiation it has been shown to participate. Like PPARalpha, it is also expressed transiently in the central nervous system. Interestingly, PPARalpha, -beta and -gamma are coexpressed at high levels in brown adipose tissue. Finally, the high and ubiquitous expression of PPARbeta suggests some fundamental role(s) that this receptor might play throughout development.

Animals↗
PubMed2000

Expression of protease-activated receptor-2 during embryonic development.

Protease-activated receptor-2 (PAR-2) is the second member of a novel family of G-protein-coupled receptors, activated through proteolytic cleavage within the extracellular domain to reveal a newly formed amino terminus that acts as a tethered ligand causing receptor activation. PAR-2 is expressed in a number of adult tissues, but its distribution during development has not been characterized. Knowledge of the tissue distribution of PAR-2 during development will provide clues as to its function(s) in vivo. In the current immunohistochemical study, a polyclonal antibody raised against a peptide corresponding to the post-cleavage amino terminal sequence of PAR-2 was used to localize PAR-2 expression in developing mouse tissues. In the developing central nervous system and cardiac muscle, PAR-2 expression was detectable at embryonic day 12 and persisted throughout embryogenesis. At embryonic day 14, PAR-2 expression was strong in peripheral nerves, but either weak or absent in skin, bone, skeletal muscle, and blood vessels. In embryonic day 17 and postnatal day 1 hindlimbs, however, PAR-2 staining was observed throughout the layers of the epidermis, in osteoblasts, muscle fibers, and in vascular smooth muscle and endothelium. The pattern of PAR-2 expression observed during embryonic development and the association of expression with differentiation in certain tissues suggest compelling physiological roles for this novel receptor.

Amino Acid Sequence↗
PubMed1996

Early expression of D3 dopamine receptors in murine embryonic development.

In order to determine whether the D2 and D3 dopamine receptors may have a role in prenatal development, we have studied the mRNA expression and distribution of these receptors during murine embryonic development. Using RT-PCR on RNA from embryos taken at progressive stages of development, we have shown that the D3 receptor is expressed significantly earlier than the D2 receptor, being detectable at day 9.5 post-conception (p.c.) compared with day 13.5 p.c. for the D2 subtype. We have also examined the mRNA distribution of the two receptors by whole mount in situ hybridisation. In agreement with the PCR assays, the D3 receptor was expressed earlier than the D2 subtype. D3 receptor transcripts were first detected at day 9.5 p.c. in the ventral aspect of the anterior neural tube, whereas D2 receptor transcripts first appeared a day later. By day 10.5-11.5 p.c. both D3 and D2 receptor transcripts were present in the developing forebrain, and later also in the branchial arches and along the prospective vertebral column. The early appearance of the D3 subtype in murine development and its predominance over the D2 subtype suggest that the D3 receptor may have a functional role in prenatal development.

Animals↗
PubMed2026

Functions and mechanisms of BRCA1 in early embryonic development.

Breast Cancer Gene 1 (BRCA1) is a critical regulator of genome integrity whose dysfunction greatly increases lifetime risk of breast and ovarian cancers. While BRCA1 has been extensively studied in the contexts of adult biology and cancer, its diverse functions, including homologous recombination-mediated DNA repair, cell cycle checkpoint activation, protein ubiquitination, and transcriptional regulation, have many underexplored implications. In early embryonic development, the maternal-to-zygotic transition (MZT) and subsequent developmental processes place extraordinary demands on DNA replication fidelity, cell cycle regulation, transcriptional activation, and chromatin remodeling. These critical processes overlap strikingly with canonical functions of BRCA1, yet its function in early development is poorly characterized. In this review, we investigate BRCA1 conservation across species and connect its well-established functions to findings from developmental studies to assess its role in development. We highlight evidence of BRCA1 mitigating genome integrity loss from diverse sources, maintaining the proliferative activity needed for successful germ layer formation and early tissue morphogenesis, and regulating transcription and epigenetic modifications. Together, this synthesis supports a model where BRCA1 acts as a multi-functional and dynamic regulator of early embryogenesis. Building on this, we propose outstanding questions that could further illuminate these developmental roles. Characterization of BRCA1 in early development may not only provide important insight into the origin and progression of cancer susceptibility but may also elucidate fundamental mechanisms shaping early development.

BRCA1 Protein↗
PubMed2003

Early embryonic development and in vitro culture of in vivo produced embryos in the farmed European polecat (Mustela putorius).

Early embryonic development and in vitro culture of in vivo produced embryos in the farmed European polecat (Mustela putorius) was investigated as a part of an ex situ conservation program of the endangered European mink (Mustela lutreola), using the European polecat as a model species. The oestrus cycles of 34 yearling polecat females were monitored by visual examination of the vulval swelling and, to induce ovulation, the females were mated once daily on two consecutive days. Sixteen yearling males were used for mating. The females were humanely killed 3-14 days after the first mating and the uteri and oviducts were collected for embryo recovery. Uterine and oviductal flushings yielded a total number of 295 embryos, representing developmental stages from the 1-cell stage to large expanded and hatched blastocysts. On Day 3 after the first mating, only 1-16-cell stage embryos were recovered. Between Days 4 and 6 after the first mating, 1-16-cell stage embryos and morulae were found. The first blastocysts were recovered on Day 7 after the first mating. The first implanted blastocysts were detected on Day 11 after the first mating. A total number of 85 embryos were in vitro cultured after recovery. Blastocyst production rates for in vitro cultured 1-16-cell stage embryos and for morulae/compact morulae were 68 and 84%, respectively. For all cultured embryos, the hatching rate was 15%. The in vitro culture requirements for the preimplantation embryos of the farmed European polecat remain to be determined before further utilization of the technique.

Animals↗
PubMed2006

Regulation of the neurofibromatosis 2 gene promoter expression during embryonic development.

Mutations in the Neurofibromatosis 2 (NF2) gene are associated with predisposition to vestibular schwannomas, spinal schwannomas, meningiomas, and ependymomas. Presently, how NF2 is expressed during embryonic development and in the tissues affected by neurofibromatosis type 2 (NF2) has not been well defined. To examine NF2 expression in vivo, we generated transgenic mice carrying a 2.4-kb NF2 promoter driving beta-galactosidase (beta-gal) with a nuclear localization signal. Whole-mount embryo staining revealed that the NF2 promoter directed beta-gal expression as early as embryonic day E5.5. Strong expression was detected at E6.5 in the embryonic ectoderm containing many mitotic cells. beta-gal staining was also found in parts of embryonic endoderm and mesoderm. The beta-gal staining pattern in the embryonic tissues was corroborated by in situ hybridization analysis of endogenous Nf2 RNA expression. Importantly, we observed strong NF2 promoter activity in the developing brain and in sites containing migrating cells including the neural tube closure, branchial arches, dorsal aorta, and paraaortic splanchnopleura. Furthermore, we noted a transient change of NF2 promoter activity during neural crest cell migration. While little beta-gal activity was detected in premigratory neural crest cells at the dorsal ridge region of the neural fold, significant activity was seen in the neural crest cells already migrating away from the dorsal neural tube. In addition, we detected considerable NF2 promoter activity in various NF2-affected tissues such as acoustic ganglion, trigeminal ganglion, spinal ganglia, optic chiasma, the ependymal cell-containing tela choroidea, and the pigmented epithelium of the retina. The NF2 promoter expression pattern during embryogenesis suggests a specific regulation of the NF2 gene during neural crest cell migration and further supports the role of merlin in cell adhesion, motility, and proliferation during development.

Animals↗
PubMed2005

Roles of JUMONJI in mouse embryonic development.

Cardiac development is a complex biological process requiring the integration of cell specification, differentiation, migration, proliferation, and morphogenesis. Although significant progress has been made recently in understanding the molecular basis of cardiac development, mechanisms of transcriptional control of cardiac development remain largely unknown. In search for the developmentally important genes, the jumonji gene (jmj) was identified by gene trap technology and characterized as a critical nuclear factor for mouse embryonic development. Jmj has been shown to play important roles in cardiovascular development, neural tube fusion process, hematopoiesis, and liver development in mouse embryos. The amino acid sequence of the JUMONJI protein (JMJ) reveals that JMJ belongs to the AT-rich interaction domain transcription factor family and more recently has been described as a member of the JMJ transcription factor family. Here, we review the roles of jmj in multiple organ development with a focus on cardiovascular development in mice.

Animals↗
PubMed2006

Vertebrate homologues of Frodo are dynamically expressed during embryonic development in tissues undergoing extensive morphogenetic movements.

Frodo has been identified as a protein interacting with Dishevelled, an essential mediator of the Wnt signaling pathway, critical for the determination of cell fate and polarity in embryonic development. In this study, we use specific gene probes to characterize stage- and tissue-specific expression patterns of the mouse Frodo homologue and compare them with Frodo expression patterns in Xenopus embryos. In situ hybridization analysis of mouse Frodo transcripts demonstrates that, similar to Xenopus Frodo, mouse Frodo is expressed in primitive streak mesoderm, neuroectoderm, neural crest, presomitic mesoderm, and somites. In many cases, Frodo expression is confined to tissues undergoing extensive morphogenesis, suggesting that Frodo may be involved in the regulation of cell shape and motility. Highly conserved dynamic expression patterns of Frodo homologues indicate a similar function for these proteins in different vertebrates.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Expression of the neurofibromatosis type 1 (NF1) gene during mouse embryonic development.

The von Recklinghausen neurofibromatosis type 1 (NF1) gene was identified by positional cloning and found to be a tumor suppressor gene expressed most abundantly in brain. One isoform of NF1 (type 2 NF1) contains an additional 21 amino acids inserted into a region of the protein involved in the regulation of p21-ras. To study the role of the NF1 gene in mammalian development, the expression of the NF1 gene and protein product, neurofibromin, during mouse embryonic development was determined. NF1 mRNA and neurofibromin expression was detectable by Northern and Western analysis, respectively, after day 10 of murine embryogenesis and remained elevated throughout development. Type 2 NF1 mRNA expression predominated before day 10, after which time, type 1 (lacking the insertion) NF1 mRNA was the predominant isoform detected. The protein expression of the type 2 isoform was similar to overall neurofibromin expression by Western blot analysis with greatest expression in adult brain. Despite a similar tissue distribution pattern, type 2 neurofibromin was not found to be associated with brain cytoplasmic microtubules in the same fashion as the uninserted type 1 isoform. Collectively, these experiments suggest that the switch from type 2 to type 1 neurofibromin isoform predominance during embryogenesis may have significant functional consequences.

Animals↗
PubMed2006

Effects of synchronization of donor cell cycle on embryonic development and DNA synthesis in porcine nuclear transfer embryos.

The relationship between donor cell cycle and the developmental ability of somatic cell nuclear transfer (SCNT) embryos has not fully been elucidated. Donor cells that are usually prepared by serum starvation or confluent-cell culture for SCNT represent a heterogeneous population that includes mainly G0 phase cells, other cells in different phases of the cell cycle and apoptotic cells. In this study, we compared the developmental ability of porcine SCNT embryos reconstructed from G0 phase cells (G0-SCNT embryos) and strictly synchronized-G1 phase cells (G1-SCNT embryos), and examined the developmental rates and timing of first DNA synthesis. The G0 phase cells were synchronized by confluent culture, and the G1 phase cells were prepared from actively dividing M phase cells. The G1-SCNT embryos showed a significantly higher (P<0.05) developmental rate to the blastocyst stage per cleaved embryo (59%) than the G0-SCNT embryos (43%). Moreover, initiation of first DNA synthesis and cleavage occurred significantly earlier in the G1-SCNT embryos than in the G0-SCNT embryos. Delay of initiation of first DNA synthesis in the SCNT embryos by aphidicolin resulted in decreased developmental rates to the blastocyst stage without any effect on cleavage rates. Our data demonstrates that synchronized-G1 phase cells can be used as donor cells for SCNT embryos and that earlier initiation of first DNA synthesis may be important for subsequent development of SCNT embryos. The SCNT system using G1-synchronized cells, in terms of their highly uniform and viable cell states, can be useful for studying the reprogramming processes and embryonic development of SCNT embryos.

Animals↗
PubMed1983

Embryonic development of the leech nervous system: primary axon outgrowth of identified neurons.

This paper describes the embryonic development of the leech nervous system and focuses on the differentiation of two identified pressure sensory (P) neurons, the PD and PV neurons. In the adult leech the P neurons have distinctive cell body locations in the central nervous system (CNS), different peripheral axon branching patterns, and different receptive field territories in the skin. The embryonic P neurons also have distinct and reproducible locations in the CNS and have been studied with recording and dye-filled microelectrodes from the time the first growth cones are projected from their somata. The peripheral axons of the P neurons are among the earliest peripheral axons to develop and may play an important role in the formation of peripheral nerves. The first or primary peripheral axons of the P neurons grow directly to their separate target territories. The specificity of the P neurons for their targets is probably not due to temporal differences in the outgrowth of their primary axons. Instead, the PD neuron seems to exhibit a preference early in embryogenesis for the target of its primary axon despite an apparent opportunity to occupy the target of the PV primary axon. It is hypothesized that the primary peripheral axons of the P neurons are among the first axons projected from the CNS and follow environmental cues to reach and innervate their target territories.

Animals↗
PubMed2006

Bovine early embryonic development and vitamin A.

Vitamin A and its derivatives, collectively termed as retinoids, have been paid attention in recent years because of their effects in bovine reproduction. However, the role of retinoids in the pre-implantation period continues to be largely unexplored, in contrast to later stages of development. Retinoids control cell growth, differentiation and death through binding to specific nuclear receptors by retinoic acid and other active metabolites. This paper reviews how retinoids can influence early embryonic development in cattle through their influence on the follicle, the extrafollicular oocyte and the pre-implantation embryo itself.

Animals↗
PubMed1999

Role of the inositol 1,4,5-trisphosphate receptor in early embryonic development.

There is now considerable literature on the importance of phosphatidylinositol cycle activation in transducing information of various types across the plasma membrane. Though much of the data derives from studies on somatic cells, there is increasing evidence for crucial events related to development, including fertilization, cell cycle progression and dorsoventral axis formation. In this review, focus is directed mainly to the molecular basis of the inositol 1,4,5-triphosphate receptor expressed in oocytes and early embryos of Xenopus. Recent progress in studies concerning the role of this receptor in early embryonic development is discussed.

Animals↗