No abstract

The key focus of this review is that both the neuroepithelium and embryonic cerebrospinal fluid (CSF) work in an integrated way to promote embryonic brain growth, morphogenesis and histiogenesis. The CSF generates pressure and also contains many biologically powerful trophic factors; both play key roles in early brain development. Accumulation of fluid via an osmotic gradient creates pressure that promotes rapid expansion of the early brain in a developmental regulated way, since the rates of growth differ between the vesicles and for different species. The neuroepithelium and ventricles both contribute to this growth but by different and coordinated mechanisms. The neuroepithelium grows primarily by cell proliferation and at the same time the ventricle expands via hydrostatic pressure generated by active transport of Na(+) and transport or secretion of proteins and proteoglycans that create an osmotic gradient which contribute to the accumulation of fluid inside the sealed brain cavity. Recent evidence shows that the CSF regulates relevant aspects of neuroepithelial behavior such as cell survival, replication and neurogenesis by means of growth factors and morphogens. Here we try to highlight that early brain development requires the coordinated interplay of the CSF contained in the brain cavity with the surrounding neuroepithelium. The information presented is essential in order to understand the earliest phases of brain development and also how neuronal precursor behavior is regulated.

Patterning along the left/right axes helps establish the orientation of visceral organ asymmetries, a process which is of fundamental importance to the viability of an organism. A linkage between left/right and axial patterning is indicated by the finding that a number of genes involved in left/right patterning also play a role in anteroposterior and dorsoventral patterning. We have recovered a spontaneous mouse mutation causing left/right patterning defects together with defects in anteroposterior and dorsoventral patterning. This mutation is recessive lethal and was named no turning (nt) because the mutant embryos fail to undergo embryonic turning. nt embryos exhibit cranial neural tube closure defects and malformed somites and are caudally truncated. Development of the heart arrests at the looped heart tube stage, with cardiovascular defects indicated by ballooning of the pericardial sac and the pooling of blood in various regions of the embryo. Interestingly, in nt embryos, the direction of heart looping was randomized. Nodal and lefty, two genes that are normally expressed only in the left lateral plate mesoderm, show expression in the right and left lateral plate mesoderm. Lefty, which is normally also expressed in the floorplate, is not found in the prospective floor plate of nt embryos. This suggests the possibility of notochordal defects. This was confirmed by histological analysis and the examination of sonic hedgehog, Brachyury, and HNF-3 beta gene expression. These studies showed that the notochord is present in the early nt embryo, but degenerates as development progresses. Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta.

If the intraluminal pressure of the brain is decreased for 24 hr, the brain and neuroepithelium volumes are both reduced in half. The current study measured the intraluminal pressure throughout the period of rapid brain growth using a servo-null micropressure monitoring system. From 613 measurements made on 55 embryos, we show that the intraluminal pressure over this time period is appropriately described by a linear model with correlation coefficient of 0.752. To assess whether sustained hyperpressure would increase mitosis, elevated intraluminal pressure was induced in 10 embryos for 1-hr duration via a gravity-fed drip. The mitotic density and index of the mesencephalon were measured for the 10 embryos. Those embryos, in which the colchicine solution was added to the intraluminal cerebrospinal fluid creating a sustained hyperpressure, exhibited at least a 2.5-fold increase in both the mitotic density and index compared with control embryos. Based on the small sample size, we cautiously conclude that sustained hyper-intraluminal pressure does stimulate mitosis.