Biomedical subjects

D Caric

Publications and source records attributed to D Caric.

3 recordsLinked to original sources

PubMed2001

EGFRs mediate chemotactic migration in the developing telencephalon.

Epidermal growth factor receptors (EGFRs) have been implicated in the control of migration in the telencephalon, but the mechanism underlying their contribution is unclear. We show that expression of a threshold level of EGFRs confers chemotactic competence in stem cells, neurons and astrocytes in cortical explants. This level of receptor expression is normally achieved by a subpopulation of cells during mid-embryonic development. Cells that express high levels of EGFR are located in migration pathways, including the tangential pathway to the olfactory bulb via the rostral migratory stream (RMS), the lateral cortical stream (LCS) leading to ventrolateral cortex and the radial pathway from proliferative zones to cortical plate. The targets of these pathways express the ligands HB-EGF and/or TGFalpha. To test the idea that EGFRs mediate chemotactic migration these pathways, we increased the size of the population of cells expressing threshold levels of EGFRs in vivo by viral transduction. Our results suggest that EGFRs mediate migration radially to the cortical plate and ventrolaterally in the LCS, but not tangentially in the RMS. Within the bulb, however, EGFRs also mediate radial migration. Our findings suggest that developmental changes in EGFR expression, together with changes in ligand expression regulate the migration of specific populations of cells in the telencephalon by a chemoattractive mechanism.

Animals↗

PubMed1999

The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex.

The cerebral cortex develops from the dorsal telencephalon, at the anterior end of the neural tube. Neurons are generated by cell division at the inner surface of the telencephalic wall (in the ventricular zone) and migrate towards its outer surface, where they complete their differentiation. Recent studies have suggested that the transcription factor Pax6 is important for regulation of cell proliferation, migration and differentiation at various sites in the CNS. This gene is widely expressed from neural plate stage in the developing CNS, including the embryonic cerebral cortex, where it is required for radial glial cell development and neuronal migration. We report new findings indicating that, in the absence of Pax6, proliferative rates in the early embryonic cortex are increased and the differentiation of many cortical cells is defective. A major question concerns the degree to which cortical defects in the absence of Pax6 are a direct consequence of losing the gene function from defective cells themselves, rather than being secondary to abnormalities in other cells. Cortical defects in the absence of Pax6 become much more pronounced later in cortical development, and we propose that many result from a compounding of abnormalities in proliferation and differentiation that first appear at the onset of corticogenesis.

Animals↗

PubMed1987

Glottic closure and high flows are not essential for productive cough.

For about 150 years, there has been emphasis on the importance of glottic closure and high flows in coughing. During voluntary coughing in normal subjects, the main expiratory flow usually begins as thoracic and abdominal pressures are rising. However, sometimes it starts at peak pressure whereas at other times flow and pressure rise together. Plateau flow in single coughs remains relatively constant in the face of large changes in pressure. In a group of coughs following a single inspiration, the fall in pressure is less during plateau flow. Consequently, for the same oral flows, it is likely that the mean linear velocity in the intrathoracic airways will be greater than in a single cough. Recordings have also been made of early morning involuntary coughing in patients with obstructive airways disease. Flow, volume and sound were recorded and sputum expectoration was noted. Sputum expectoration usually occurs after groups of coughs following single inspirations. Hence the movement of the equal pressure point peripherally may be important. These patients have very low flows and yet their coughs are productive. Sound often occurs during the whole of the low flow period immediately before the main expulsive phase. This could only occur if the glottis was open. Thus productive cough can occur without glottic closure and with low airflows.

Asthma↗