Zona Limitans Intrathalamica - Discovery

Discovery

Cell lineage restriction boundaries, across which replicating cells cannot migrate, were first discovered in invertebrates, where the expression of various Hox genes in each compartment confer the differentiation of observable segments in the adult body of Drosophila melanogaster. Analogous structures were discovered in the developing vertebrate brain. Rhombomeres, which extend down the embryo from the hindbrain, contain clear boundaries and each express various Hox genes that are necessary for differentiation of structures within the body. More anterior regions of the brain were examined in search of other cell lineage restriction boundaries, and multiple potential boundaries continue to be studied (see Developmental Boundaries).

The importance of these compartments as local signaling centers, areas which chemically influence surrounding tissue, was elucidated by first observing differential expression of Hox genes in various compartments and second by observing mutant D. melanogaster and corresponding phenotypic (physical) changes.

The ZLI was first discovered in the chick using explant and lineage-labeling experiments. In the explant experiments, cells in the region that will become the ZLI, the prethalamus, and the thalamus in the chick were removed and placed into separate cultures; the cells continued to grow and retained their identity (the ZLI began transcribing, whereas the prethalamus and thalamus did not). Necessity of the ZLI and its corresponding ' expression were evidenced by lack of thalamic and prethalamic genetic markers in culture (see Signaling). These experiments confirmed the ZLI as a signaling center. In lineage-labeling experiments, cells were genetically marked, so that each time a labeled cell replicated, its progeny were marked as well. Cells that were marked in the developing ZLI and their progeny remained restricted to the zone. These experiments demonstrated the ZLI as a cell-lineage restriction boundary.

Not only a boundary, the ZLI is also a compartment with separate cell lineage restriction boundaries both anterior and posterior of a section of shh expression. The importance of the ZLI was once more confirmed by ectopic expression of shh in other regions of the forebrain, known as the prosencephalon during development (both the telencephalon and diencephalon), inducing a ZLI-like region that induces thalamic fate.