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Biomedical subjects

M Hajihosseini

Publications and source records attributed to M Hajihosseini.

6 recordsLinked to original sources

An important role for the IIIb isoform of fibroblast growth factor receptor 2 (FGFR2) in mesenchymal-epithelial signalling during mouse organogenesis.

The fibroblast growth factor receptor 2 gene is differentially spliced to encode two transmembrane tyrosine kinase receptor proteins that have different ligand-binding specificities and exclusive tissue distributions. We have used Cre-mediated excision to generate mice lacking the IIIb form of fibroblast growth factor receptor 2 whilst retaining expression of the IIIc form. Fibroblast growth factor receptor 2(IIIb) null mice are viable until birth, but have severe defects of the limbs, lung and anterior pituitary gland. The development of these structures appears to initiate, but then fails with the tissues undergoing extensive apoptosis. There are also developmental abnormalities of the salivary glands, inner ear, teeth and skin, as well as minor defects in skull formation. Our findings point to a key role for fibroblast growth factor receptor 2(IIIb) in mesenchymal-epithelial signalling during early organogenesis.

Abnormalities, Multiple↗

Origin of oligodendrocytes within the human spinal cord.

To determine the time and site of origin of the oligodendrocyte lineage in the developing human spinal cord, we have examined tissues from 45 to 83 d postconception (dpc) using sets of probes and antibodies recognizing oligodendrocyte-specific glycolipids, transcripts, and proteins. We found that two clusters of oligodendrocyte precursors appear on or before 45 dpc on each side of the cord ventral ependyma above the floor plate. These precursors express glycolipids recognized by the O4 and Rmab antibodies, platelet-derived growth factor alpha-receptor, myelin basic protein (MBP), and 2', 3'-cyclic nucleotide 3' phosphodiesterase as well as MBP and proteolipid transcripts. Expression of the morphogen sonic hedgehog was detected in the floor plate at 45 dpc and decreased at 58 dpc. During this period, oligodendrocyte precursors emerged in the ventral and lateral region of the forming white matter, a process occurring first in cervical and later in lumbar cord. The majority of O4(+) cells express the proliferating cell nuclear antigen (PCNA), and their pattern of dispersion suggests that these cells progressively populate the lateral and dorsal cord regions. Oligodendrocytes expressing galactocerebroside appeared at 53 dpc and did not express PCNA. Oligodendrocyte precursors were detected in dorsal cord regions at 74 dpc and at 83 dpc when myelination started in the ventral roots. Thus, oligodendrocyte precursors expressing myelin transcripts and proteins emerge in the ventral region of the embryonic cord several weeks before myelination.

Cell Line↗

Evidence that retroviruses integrate into post-replication host DNA.

We have studied the question of whether a retrovirus integrates into the chromosomal DNA of the host cell before or after the DNA is replicated during the S phase of the cell cycle. We have infected single NIH-3T3 cells with BAG, a replication-incompetent retroviral vector which encodes the lacZ gene, then observed the clones derived from these cells to discover whether all the cells carry a copy of the proviral DNA. We have discovered that only half of the progeny of an infected cell carries a copy of the provirus. This indicates that the virus only integrates into post-replication DNA. We discuss the implications of this result for applications of retroviruses, such as gene therapy and cell lineage, which use them as vehicles for gene transfer into stem cells.

3T3 Cells↗

Multiple restricted lineages in the embryonic rat cerebral cortex.

We have labelled precursor cells in the embryonic rat cerebral cortex using BAG, a retroviral vector that expresses beta-galactosidase. We had previously reported that labelled precursor cells generate clusters of labelled cells that could be classified into four types by their morphological appearance and anatomical distribution (Price and Thurlow, 1988). In this study, we have used immunohistochemistry and intracellular dye labelling to identify the cell types that make up these clusters. We discovered that clusters are almost always composed of a single cell type. In addition to clusters composed entirely of neurones, we found four different types of glial cell clusters. In the grey matter, glial clusters are composed either of protoplasmic astrocytes, or of cells that have an astrocyte morphology, but no glial filaments. In the white matter, clusters are composed of either fibrous astrocytes or oligodendocytes. Our results indicate that each of these different cortical cell types is generated from a separate population of precursor cells.

Animals↗