Neuromere

Abstract: We have examined the transcript distribution of six members of the murine paired box-containing gene family (Pax-gene family) in midgestation embryo and adult brain using in situ hybridization analysis. The expression domains of several Pax-genes in the embryo brain were found to correspond with anatomical boundaries that coincide with neuromere landmarks and therefore respect former neuromere territories in the forebrain. The results are consistent with the concept of brain segmentation and suggest a role for Pax-genes in the brain regionalization. In the adult brain the expression of Pax-genes was observed in discreet areas, with a caudal to rostral restriction in the number of the expressed genes. In general the distribution of transcripts along the anterior-posterior axis was similar to that found in midgestation embryo brain, suggesting a role for Pax-genes in the commitment of the precursor cells to different neuronal cell fates and in the maintenance of specific brain cell subtypes. In the cerebellar cortex, the granular cell layer was found to express high levels of the Pax-6 gene, while putative Bergmann glia and cells surrounding the Purkinje cells contained Pax-3 transcripts. The main adult brain structures that expressed distinct Pax-mRNAs were the periglomerular and granular cell layer of olfactory bulb, nuclei of the septum, amygdala, and isthmus, which suggests a role for the Pax-gene family in the specification of the subcortical domains of the evolutionary old limbic system.

Abstract: Beads containing recombinant FGF8 (FGF8-beads) were implanted in the prospective caudal diencephalon or midbrain of chick embryos at stages 9–12. This induced the neuroepithelium rostral and caudal to the FGF8-bead to form two ectopic, mirror-image midbrains. Furthermore, cells in direct contact with the bead formed an outgrowth that protruded laterally from the neural tube. Tissue within such lateral outgrowths developed proximally into isthmic nuclei and distally into a cerebellum-like structure. These morphogenetic effects were apparently due to FGF8-mediated changes in gene expression in the vicinity of the bead, including a repressive effect on Otx2 and an inductive effect on En1, Fgf8 and Wnt1 expression. The ectopic Fgf8 and Wnt1 expression domains formed nearly complete concentric rings around the FGF8-bead, with the Wnt1 ring outermost. These observations suggest that FGF8 induces the formation of a ring-like ectopic signaling center (organizer) in the lateral wall of the brain, similar to the one that normally encircles the neural tube at the isthmic constriction, which is located at the boundary between the prospective midbrain and hindbrain. This ectopic isthmic organizer apparently sends long-range patterning signals both rostrally and caudally, resulting in the development of the two ectopic midbrains. Interestingly, our data suggest that these inductive signals spread readily in a caudal direction, but are inhibited from spreading rostrally across diencephalic neuromere boundaries. These results provide insights into the mechanism by which FGF8 induces an ectopic organizer and suggest that a negative feedback loop between Fgf8 and Otx2 plays a key role in patterning the midbrain and anterior hindbrain.