Zona limitans intrathalamica

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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.[1][2]

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.[3]

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.[4] 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.[5]

Studies in chick have shown that Shh is necessary and sufficient for both prethalamic expression of Dlx2 and thalamic expression of Gbx2 and Sox14.[6] In zebrafish, the structure corresponding to the Shh expression has been termed as mid-diencephalic boundary (MDB)[7][8] but subsequently referred to as ZLI,[9] 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.[8] 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.[8]

File:Zona limitans intrathalamica.jpg

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[8]


  1. Kuhlenbeck, H (1937). "The ontogenetic development of diencephalic centres in the bird's brain (chick) and comparison with the reptilian and mammalian diencephalon". J. Comp. Neurol. 66.
  2. Shimamura, K. (1995). "Longitudinal organization of the anterior neural plate and neural tube". Development. 121 (12): 3923–33. PMID 8575293. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  3. Zeltser, L. (2001). "A new developmental compartment in the forebrain regulated by Lunatic fringe". Nat. Neurosci. 4 (7): 683–4. PMID 11426219. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  4. Puelles, L (2003). "Forebrain gene expression domains and the evolving prosomeric model". Trends Neurosci (9): 469–76. PMID 12948657. Unknown parameter |voume= ignored (help); Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  5. Ishibashi, M (2002). "A sonic hedgehog-dependent signalling relay regulates growth of diencephalic and mesencephalic primordia in the early mouse embryo". Development. 129 (20): 4807–19. PMID 12361972. Unknown parameter |coauthors= ignored (help)
  6. Kiecker, C. (2004). "Hedgehog signalling from the ZLI regulates diencephalic regional identity". Nat. Neurosci. 7 (11): 1242–9. PMID 15494730. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  7. Macdonald R (1994). "Regulatory gene expression boundaries demarcate sites of neuronal differentiation in the embryonic zebrafish forebrain". Neuron. 13 (5): 1039–53. PMID 7946344. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  8. 8.0 8.1 8.2 8.3 Scholpp S (2006). "Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon". Development. 133 (5). PMID 16452095. Unknown parameter |coauthors= ignored (help); Unknown parameter |month= ignored (help)
  9. Barth, K. A. (1995). "Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain". Development. 121 (6): 1755–68. PMID 7600991. Unknown parameter |coauthors= ignored (help)