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PubMed1993

Midline structures and central nervous system coordinates in zebrafish.

The embryonic zebrafish provides a relatively simple and accessible experimental system for understanding the underlying Bauplan of a vertebrate central nervous system (CNS) and for uncovering interactions critical for patterning. We show that features of CNS organization in normal, mutant, and developmentally ventralized zebrafish embryos can be explained by a three-axis hypothesis: Specifications occur according to position relative to coordinates along the anterior-posterior, dorsal-ventral, and luminal-pial axes of the neural tube. Midline tissues may be responsible for directly establishing the dorsal-ventral coordinates, but may only be indirectly involved in patterning along the anterior-posterior axis.

Animals↗
PubMed1993

Pathway selection by growth cones in the zebrafish central nervous system.

The accessibility and simplicity of the zebrafish embryo have led to a detailed characterization of pathfinding by identifiable growth cones in both the spinal cord and brain. These growth cones follow precise, cell-specific pathways to their targets. Analyses of pathfinding in mutant embryos and wild-type embryos following laser ablation or transplantation of specific cells demonstrate that growth cones accomplish this by interacting with specific cellular cues in their environment, many of which are likely to be redundant. These experiments suggest that a combination of separate pathway and directionality cues are required for pathfinding by growth cones. Growth cones distinguish different pathways by sensing specific pathway cues and know what direction they should extend on a pathway by sensing widely distributed directionality cues.

Animals↗
PubMed1976

Correlation between the cell cycle in the neurectoderm and differentiation during the early development of Xenopus laevis. 1. BUdR sensitivity during gastrulation.

An hypothesis has been proposed by Holtzer and co-workers (1963, 1970, 1973) that the process of cell differentiation may be coupled in an obligatory manner with 'Quantal' cell cycle(s) which precede it. We have demonstrated that a 'wave' of DNA synthesis occurs in the neurectoderm of Xenopus laevis gastrula. This event of the cell cycle appears to be associated with the primary embryonic induction by the subjacent mesodermal tissue. The peak of DNA synthesis was observed in that area of the neurectoderm which was overlying the pre-chordal plate of mesoderm. Administration of 5-bromodeoxyuridine (BUdR) into the DNA of cells in a critical phase preceding overt differentiation, is known to perturb cytodifferentiation. In the present work sensitivity of X. laevis gastrula to BUdR (10(-3) M) has been investigated so as to assess the significance for neurogenesis of the wave of DNA synthesis in the neurectoderm.

Abnormalities, Drug-Induced↗
PubMed1993

[The role of vitamin A analogues and derivatives in the regulation of cell function].

The vitamin A and the retinoids, the vitamin A derivatives play an important role in the embryogenesis, in the modulation of the growth, in the differentiation of normal, premalignant and malignant epithelial and mesenchymal cells and in the maintenance of immune response. The effects of vitamin A are executed by two different mechanisms. While the carotenoids of provitamin A activity and the vitamin A--the retinol--itself are mainly antioxidant molecules and so some of their effects are partly similar to the effects of tocopherol, the retinoids, the derivatives of vitamin A, exert their diverse effects by regulating the expression of specific genes by the aid of specific nuclear receptors belonging to the family of steroid, thyroid hormone, and vitamin D3 receptors. The retinoids play a role in the modulation of the effect of these hormones as well.

Antioxidants↗
PubMed1995

Immunohistochemical localization of antioxidant enzymes during hamster kidney development.

Immunolocalization studies of hamster kidney development were performed using polyclonal antibodies to antioxidant enzymes, including antibodies to copper, zinc and manganese superoxide dismutases, catalase, glutathione peroxidase and glutathione S-transferases and their subunits. Antibodies to extracellular matrix proteins were also studied to determine the temporal sequence between expression of immunoreactive protein for basement membrane proteins, which serve as markers of embryonic induction of nephron development, and antioxidant enzyme expression in kidney development. Immunoreactive proteins for antioxidant enzymes were not detectable in the developing kidney until after extracellular matrix proteins had been deposited. However, immunoreactive proteins for the antioxidant enzymes copper, zinc and manganese superoxide dismutases, catalase, and alpha class glutathione S-transferase Ya subunit were detected in renal tubules before birth. mu class glutathione S-transferase subunits Yb1 and Yb2 stained transitional epithelium at high levels before birth. Our results indicate: (1) each type of kidney cell has a unique antioxidant enzyme profile, (2) antioxidant enzymes are expressed in different types of cell at different times during development, but antioxidant enzyme immunoreactive protein was not present until after immunoreactive proteins for extracellular matrix molecules were detected, and (3) certain antioxidant enzymes are present before birth, indicating that high oxygen tension present at birth is not crucial for induction of immunoreactive protein.

Animals↗
PubMedDate not supplied

Endochondral and intramembranous fetal bone development: osteoblastic cell proliferation, and expression of alkaline phosphatase, m-twist, and histone H4.

We have previously studied the expression of alkaline phosphatase (ALP) and alpha2(I) collagen (two phenotypic markers of osteoblastic cell differentiation) during development of the rat mandible, and the spatial and temporal distribution of the respective transcripts. Our current studies utilize the rat mandible and hind foot as in vivo model systems to investigate the relationship between osteoblastic differentiation and proliferation during intramembranous and endochondral bone formation. Pregnant rats, at 15.17, and 19 days of gestation were intraperitoneally injected with various doses of [3H]-thymidine, and sacrificed at various time intervals in order to label dividing embryonic osteoblastic and preosteoblastic cells. Cross sections through the mid-body of 15-day embryos showed [3H-thymidine dose-dependent labeling of a relatively high percentage of cells in the liver (49 +/- 8% at 440 muCi) and a lower percentage of cells of the developing vertebral cartilage (29 +/- 6% at 440 muCi). ALP-positive condensed mesenchyme--consisting of mandibular preosteoblast (15 days of gestation) showed a relatively high (32 +/- 5%) level of [3H]-thymidine labeling, compared to surrounding ALP-negative loose mesenchymal cells (22 +/- 1%). Similar results were observed in the developing hind foot of 19-day embryos for ALP-positive cells (15 +/- 6%) and surrounding ALP-negative cells (13 +/- 5%). In both the hind foot and the mandible an overall decrease in labeling was observed during bone development. RNA samples from these tissues show increasing amounts of ALP mRNA, and decreasing amounts of histone H4 mRNA between days 15 and 19 of gestation. These data indicate that a general inverse correlation between osteoblastic differentiation and proliferation, similar to the correlation previously described in cultured osteogenic cells, is also present in developing bones in vivo. However, these results indicate that ALP-positive preosteoblasts, committed to the osteoblastic lineage, maintain their proliferative capacity. In an attempt to elucidate underlying molecular mechanisms, we further investigated the levels of expression of m-twist in these tissues. This member of the basic helix-loop-helix family of transcription regulators has been previously implied as playing a role in osteoblast differentiation in culture. Our results demonstrate a decrease in m-twist levels during bone development in both the mandible and the hind foot.

Alkaline Phosphatase↗
PubMed1997

Cell lineage determination and the control of neuronal identity in the neural crest.

The molecular mechanisms underlying the determination of neuronal identity in the vertebrate peripheral nervous system are only just beginning to come into focus. Many of these mechanisms, such as the involvement of cascades of bHLH transcription factors and lateral inhibition via the Notch-Delta system, appear to have been conserved from Drosophila (Ghysen et al. 1993; Jan and Jan 1993). The way in which these genetic circuits are controlled by instructive growth factors, and the manner in which they lead to expression of a particular neuronal identity, is far from clear. This process is being elucidated by studies of neurogenesis in the peripheral autonomic lineage, which is arguably the best-understood neurogenic lineage in vertebrates. Emerging evidence is beginning to suggest that neuronal diversity within the autonomic and sensory lineages may be generated by related, but distinct, mechanisms. All autonomic progenitors express a common bHLH protein, MASH1, which appears to be induced by members of the BMP2 subfamily secreted by the tissues to which these progenitors migrate. Additional signals may then act on these progenitors in different locations to induce the expression of other transcription factors, which act in conjunction with MASH1 to specify the final phenotypes of the different autonomic neuron subtypes (sympathetic, parasympathetic, and enteric). Although different classes of autonomic neurons develop in very different locations within the body, different classes of sensory neurons are located together in dorsal root ganglia. The finding that distinct but related subtypes of bHLH proteins, the neurogenins, are expressed by different classes of sensory neuron precursors early in development suggests that sensory neuron diversity, in contrast to autonomic neuron diversity, may be pre-specified at or before the time neural crest cells begin their emigration from the neural tube.

Animals↗