Zona limitans intrathalamica

The zona limitans intrathalamica (ZLI) is a transverse boundary located between the prethalamus (previously also known as ventral thalamus) and the functional distinct thalamus (dorsal thalamus.

Besides its morphological characteristics, it bears the hallmarks of a signalling centre. Fate mapping experiments in chick have shown that the ZLI is cell lineage restricted at its boundaries and therefore can be termed a true developmental compartment in the forebrain.

Besides morphological characteristics, the ZLI is the only structure in the alar plate of the neural tube that expresses the signalling molecule Sonic hedgehog; Shh. In mouse, the function of Hh signalling at the ZLI has not been addressed directly due to a complete absence of the diencephalon in Shh mutants.

Studies in chick have shown that Shh is necessary and sufficient for both prethalamic expression of Dlx2 and thalamic expression of Gbx2 and Sox14. In zebrafish, the structure corresponding to the Shh expression has been termed as mid-diencephalic boundary (MDB) but subsequently referred to as ZLI, in keeping with pre-existing terminology for other vertebrates. In zebrafish, it was shown that the expression of two shh genes, shh-a and shh-b (formerly described as twhh) mark the ZLI territory, and that ZLI development is accompanied by expression of pro-neural genes: anteriorly of dlx2a, a marker of the prethalamus, and posteriorly of dbx1a, a marker of the thalamus. Shh signalling is sufficient for the molecular differentiation of both the prethalamus and the thalamus but is not required for their maintenance and Shh signalling from the ZLI in the alar plate is sufficient for the maturation of prethalamic and thalamic territory while ventral Shh signals are dispensable.



The Zona limitans intrathalamica (ZLI) expresses the Sonic-hedgehog (Shh) gene. The picture show a lateral view of the brain of a zebrafish embryo at 42 post fertilisation after double in situ hybridization with a probe against shh-a and dlx2a. The ZLI (red) marks the V-shaped boundary between the two Prethalami (PT; blue) and Thalamus (Th; yellow) in a pseudo-frontal view. by Steffen Scholpp