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. [cite journal
first=H
last= Kuhlenbeck
year=1937
title=The ontogenetic development of diencephalic centres in the bird's brain (chick) and comparison with the reptilian and mammalian diencephalon
journal=J. Comp. Neurol.
volume=66
doi=10.1002/cne.900660103
pages=23] [cite journal
author=Shimamura, K.
coauthors=Hartigan, D. J., Martinez, S., Puelles, L. and Rubenstein, J. L.
year=1995
title=Longitudinal organization of the anterior neural plate and neural tube
journal=Development
volume=121
issue=12
month=Dec
pages=3923–33
pmid=8575293 ]

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. [cite journal
author=Zeltser, L.
coauthors=M., Larsen, C. W. and Lumsden, A.
year=2001
title=A new developmental compartment in the forebrain regulated by Lunatic fringe
journal=Nat. Neurosci.
volume=4
issue=7
month=Jul
pages=683–4
pmid=11426219
doi=10.1038/89455 ]

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. [cite journal
author=Puelles, L
coauthors=Rubenstein, J. L.
year=2003
title=Forebrain gene expression domains and the evolving prosomeric model
journal=Trends Neurosci
voume=26
issue=9
month=Sep
pages=469–76
pmid=12948657
doi=10.1016/S0166-2236(03)00234-0
volume=26] 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. [cite journal
author=Ishibashi, M
coauthors=McMahon, A. P.
year=2002
title=A sonic hedgehog-dependent signalling relay regulates growth of diencephalic and mesencephalic primordia in the early mouse embryo
journal=Development
volume=129
issue=20
pages=4807–19
pmid=12361972 ]

Studies in chick have shown that Shh is necessary and sufficient for both prethalamic expression of Dlx2 and thalamic expression of Gbx2 and Sox14. [cite journal
author=Kiecker, C.
coauthors=Lumsden, A.
year=2004
title=Hedgehog signalling from the ZLI regulates diencephalic regional identity
journal=Nat. Neurosci
month=Nov
volume=7
issue=11
pages=1242–9
pmid=15494730
doi=10.1038/nn1338] In zebrafish, the structure corresponding to the Shh expression has been termed as mid-diencephalic boundary (MDB) [cite journal
author=Macdonald R
coauthors=Xu Q, Barth KA, Mikkola I, Holder N, Fjose A, Krauss S, Wilson SW. |title=Regulatory gene expression boundaries demarcate sites of neuronal differentiation in the embryonic zebrafish forebrain
journal=Neuron
year=1994
month=Nov
volume=13
issue=5
pages=1039–53
pmid=7946344 |doi=10.1016/0896-6273(94)90044-2 ] cite journal
author=Scholpp S
coauthors=Wolf O, Brand M, Lumsden A.
title=Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon
journal=Development
year=2006
month=Mar
volume=133
issue=5
pmid=16452095
doi=10.1242/dev.02248
pages=855 ] but subsequently referred to as ZLI, [cite journal
author=Barth, K. A.
coauthors=Wilson, S. W.
year=1995
title=Expression of zebrafish nk2.2 is influenced by sonic hedgehog/vertebrate hedgehog-1 and demarcates a zone of neuronal differentiation in the embryonic forebrain.
journal=Development
volume=121
issue=6
pages=1755–68
pmid=7600991] 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"

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