Zona Limitans Intrathalamica - Signaling

Signaling

After establishment of the ZLI, shh has been shown to induce expression of thalamic and prethalamic markers, gbx2 and dlx2/ nkx2.1, respectively. This differential induction most likely is due to the expression of genes such as irx3 in the thalamus: ectopic expression experiments showed that if irx3, which is normally expressed in the developing thalamus, is expressed anterior to the ZLI, then the developing prethalamus will change identity. Note that these genes which help confer shh competence help to pattern the ZLI.

Signaling from the ZLI cooperating with thalamic and prethalamic markers ensures the migration of post-mitotic (neural progenitor) cells to the mantle zone where the cells assemble into nuclei characteristic of the thalamus. These nuclei are the mechanism of the relay of information from the thalamus to the cortex. The thalamus itself is highly diverse, with each nucleus having distinct morphologies and physiologies according to the region of the brain to which it is connected. These differences are thought to originate in differential gene expression in the thalamus and prethalamus, which allows for a single structure with multiple different and separate functions once the two have merged and completed growth and differentiation. So an functional interplay between Shh from the ZLI and the bHLH factor Her6 (homolog to HES1) determines the neuronal identity within the thalamus: Her6 positive cells in the prethalamus and rostral thalamus differentiate into GABAergic inhibitory neurons, whereas her negative cells become glutamatergic relay neurons. Both cell types depend on Shh signal as trigger to initiate the developmental programme.