Biomedical subjects

J M Gad

Publications and source records attributed to J M Gad.

7 recordsLinked to original sources

PubMed2001

Morphogenetic tissue movement and the establishment of body plan during development from blastocyst to gastrula in the mouse.

In many animal species, the early development of the embryo follows a stereotypic pattern of cell cleavage, lineage allocation and generation of tissue asymmetry leading to delineation of the body plan with three primary embryonic axes. The mammalian embryo has been regarded as an exception and primary body axes of the mouse embryo were thought to develop after implantation. However, recent findings have challenged this view. Asymmetry in the fertilised oocyte, as defined by the position of the second polar body and the sperm entry point, can be correlated with the orientation of the animal-vegetal and the embryonic-abembryonic axes in the preimplantation blastocyst. Studies of the pattern of morphogenetic movement of cells and genetic activity in the peri-implantation embryo suggest that the animal-vegetal axis of the blastocyst might presage the orientation of the anterior-posterior axis of the gastrula. This suggests that the asymmetry of the zygote that is established at fertilisation and early cleavage has a lasting impact on the delineation of body axes during embryogenesis.

Animals↗

PubMed2000

The spatial and temporal expression patterns of netrin receptors, DCC and neogenin, in the developing mouse retina.

Recently it has been demonstrated that the guidance of retinal ganglion cell (rgc) axons through the optic disc is dependent on the DCC/netrin-1 axonal guidance system. To gain further insight into the function of the netrin receptors, DCC and Neogenin, in retinal development we have studied the expression patterns of these receptors in the embryonic mouse retina. Neogenin mRNA was restricted to a single neural cell type, the rgc. However, strong Neogenin mRNA expression was observed in the extending fiber cells of the developing lens suggesting a role for Neogenin in the migration events shaping the early lens. Our studies demonstrated that DCC mRNA was expressed at high levels in chains of closely opposed neurons as they migrated towards the emerging mantle layer in the early retina (E12.5-E13.5) suggesting a role for DCC in the migration of neurons out of the ventricular zone. DCC protein expression was high on rgc axons as they actively navigated through the optic disc into the optic nerve. At birth, when the majority of rgc axons had projected through the optic disc, DCC protein was no longer detectable on the distal axonal segments within the optic nerve despite significant DCC protein expression on the proximal axonal membranes in the nerve fiber layer. These observations suggest that a localized down-regulation of DCC protein occurs on projecting axonal membranes once the DCC guidance function is no longer required. We also demonstrated that DCC mRNA and protein were expressed by amacrine cells and Müller glial cells while DCC mRNA was detected in horizontal cells. Taken together, these expression patterns suggest a role for DCC in axon outgrowth and/or pathfinding for a variety of retinal neurons and in the migration of newly born neurons within the developing retina.

Animals↗

PubMed1999

Axis development: the mouse becomes a dachshund.

Targeted deletion of the gene for GDF11, a novel member of the TGFbeta family, has been found to cause an increase in the number of thoracic and lumbar vertebrae in the mouse. This is the first hint that a secreted factor may influence the specification of segment identity.

Abnormalities, Multiple↗

PubMed1999

The Deleted in Colorectal Cancer netrin guidance system: a molecular strategy for neuronal navigation.

1. Neuronal migration is one of the principal events in laying out the architectural plan of the embryonic central nervous system (CNS). In addition, the correct navigation of axonal growth cones to their specific targets is essential for the establishment of the intricate network of axon projections found within the mature CNS. 2. The Deleted in Colorectal Cancer (DCC) guidance receptor, together with its ligands, the netrins, is now emerging as a major navigational system driving both neuronal and axonal migrations. Members of the netrin family of secreted guidance cues are also likely to be ligands for a second DCC-like receptor, neogenin. 3. The present paper reviews the current understanding of DCC-netrin-dependent axon pathfinding within the embryonic spinal cord and suggests novel modes of action for both DCC and neogenin.

Animals↗

PubMed1997

The expression patterns of guidance receptors, DCC and Neogenin, are spatially and temporally distinct throughout mouse embryogenesis.

To gain a better understanding of the role of DCC and Neogenin in neural and nonneural tissues during vertebrate development we have carried out in situ hybridization studies to determine their expression patterns throughout the mid to late stages of mouse embryogenesis. This analysis revealed striking contrasts in both the spatial and temporal expression patterns of these closely related molecules. While DCC mRNA expression was predominantly restricted to the developing central nervous system (CNS), Neogenin mRNA was detected in a broad spectrum of embryonic tissues. Outside the CNS, Neogenin expression was observed mainly in mesodermal derivatives such as organ primordia and cartilage condensations of many developing embryonic structures. Within the CNS, initiation of DCC expression correlated with the onset of neurogenesis and was maintained at high levels in all regions of the developing CNS actively undergoing neurogenesis. By E18.5, DCC expression was detected only in structures such as the olfactory bulb, the hippocampus, and the cerebellum, that are known to sustain active neurogenesis well into postnatal life. In contrast, Neogenin expression was weak in the early developing CNS but broadened and intensified as neurogenesis proceeded. In summary, these observations indicate that Neogenin is the predominant member of this subfamily in mesodermal tissues, while DCC and Neogenin may play complementary roles in the generation of the fully functional CNS.

Animals↗

PubMed1997

Mouse Neogenin, a DCC-like molecule, has four splice variants and is expressed widely in the adult mouse and during embryogenesis.

Neogenin is a member of the N-CAM family of cell adhesion molecules and is closely related to the DCC tumor suppressor gene product. Recently, it has been demonstrated that the DCC/Neogenin subfamily plays a key role in axonal guidance within the embryonic nervous system, however little is known about the function of DCC or Neogenin in non-neuronal tissues in vertebrates. To gain an understanding of Neogenin function outside of the nervous system we have cloned and sequenced the mouse homologue of Neogenin. We describe three alternatively spliced exons within the extracellular domain of Neogenin and a fourth alternatively spliced exon within the cytoplasmic domain. We further demonstrate that three of these alternatively spliced exons are developmentally regulated. Analysis of Neogenin mRNA expression showed that two distinct Neogenin transcripts are expressed at significant levels in a broad spectrum of adult mouse tissues and throughout the mid to late stages of embryogenesis. In situ hybridization studies on day 15.5 mouse embryos revealed that Neogenin is expressed widely throughout the developing mouse embryo, in both neuronal and non-neuronal tissues. These observations suggests that Neogenin may play an integral role in regulating differentiation programmes and/or cell migration events within many embryonic and adult tissues.

Alternative Splicing↗

PubMed1997

Placenta growth factor and vascular endothelial growth factor are co-expressed during early embryonic development.

We have used the polymerase chain reaction to identify mouse proteins similar in primary structure to the endothelial cell mitogen Vascular Endothelial Growth Factor (VEGF). One amplified product encoded mouse Placenta Growth Factor (PIGF). The pattern of PIGF gene expression in mouse embryos was studied by in situ hybridization. Transcripts encoding mouse PIGF were abundant in trophoblastic giant cells associated with the parietal yolk sac at early stages of embryogenesis. VEGF transcripts were also detected in trophoblastic giant cells raising the possibility that these cells may secrete heterodimers consisting of one PIGF subunit and one VEGF subunit. The secretion of PIGF and VEGF by trophoblastic giant cells is likely to be the signal which initiates and co-ordinates vascularization in the deciduum and placenta during early embryogenesis.

Amino Acid Sequence↗