Sites of origin and patterns of migration of vasotocin/mesotocin neurons in developing brain of the chick.

Vasotocin/mesotocin (VT/MT) producing neurons are known to migrate extensively during development of the hypothalamus. Birthdating studies as well as immunohistochemical studies suggested the possibility that VT/MT producing neurons originate from specific sites of the neural tube. Furthermore, a relationship between the site of origin and the eventual fate of VT/MT cells has been suggested. This study proposes to identify the sites of origin of VT/MT cells and to establish whether magnocellular and parvocellular VT/MT, and neuromodulatory and neurosecretory VT/MT arise from common or different areas of the developing neural tube. To do so, the embryological distribution of VT/MT producing neurons of the chick was studied with immunohistochemistry. Analysis of the youngest brains in which VT/MT cells could be detected (embryonic day 7.25, E7.25) suggested the presence of two separate sites of origin. The first site was located in the hypothalamic anlage, next to the third ventricle, and the second in the mesencephalon, next to the fourth ventricle. Three-dimensional reconstructions of the location of VT/MT cells throughout development substantiated the hypothesis that diencephalic VT/MT cells originate from the first site while mesencephalic ones originate from the second site. Mesencephalic VT/MT producing cells were confined to the nucleus of Edinger-Westphal and were only detectable during a brief period in development (E7.25-E10). Diencephalic VT/MT producing neurons were noted to form two main paths from their sites of origin to the rostral diencephalon. Quantitative analysis confirmed this caudal to rostral displacement. Magnocellular and parvocellular VT/MT+ cells were intermingled at the diencephalic site of origin as well as in the migratory paths. Neuromodulatory and neurosecretory VT/MT cells of the diencephalon appeared to be derived from a common diencephalic site of origin. These studies support the hypothesis that while specific groups of progenitors may be important in allowing their offspring to produce VT/MT, they do not appear to influence the morphological attributes (magnocellular vs. parvocellular), nuclear locations, or functional characteristics of these cells.

Dispersion patterns of clonally related cells during development of the hypothalamus.

To identify patterns of cell generation and migration during early development of the hypothalamus, clones were marked with a library of retroviral vectors. The majority of clones analyzed at Embryonic Days 8-10 were simple radial columns. A small number of clones had one of three unusual patterns of dispersion. One unusual clone type was bilaterally symmetric across the ventral forebrain. Another was composed of four or more columns of cells arranged in a line along the ventricular surface, and a third was composed of cells that appeared to disperse from the typical radial columns in a plane parallel to the ventricular surface. The appearance of the rare clones suggests that there are different mechanisms of clonal dispersion during early development of the ventral forebrain that could play a role in patterning the hypothalamus.

The effect of the inhibition of prostaglandin synthesis on renal blood flow in fetal sheep.

Treatment with prostaglandin synthesis inhibitors has been associated with oligohydramnios in the fetus. The presumed mechanism is a reduction in fetal renal blood flow. We examined the effect of meclofenamate administration on renal blood flow in chronically catheterized fetal sheep during normoxia and during moderate and severe hypoxia. Ten fetal sheep were made hypoxic twice at least 4 days after surgery: once in the presence and once in the absence of meclofenamate infusion. Renal blood flow and combined ventricular output were measured with radioactive microspheres. Prostaglandin synthesis blockade with meclofenamate caused no significant change in blood pressure, combined ventricular output, renal blood flow, or renal vascular resistance in either the normoxic or hypoxic animals. These data challenge the contention that prostaglandin activity protects the renal vascular bed of the fetus from vasoconstriction during hypoxia and they also do not support the hypothesis that prostaglandin synthesis inhibition causes oligohydramnios through reduction of fetal renal blood flow.