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Nature Neuroscience
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Hedgehog signaling from the ZLI regulates diencephalic regional identity

Nature Neurosciencevolume 7, pages1242–1249 (2004)Cite this article

Abstract

The zona limitans intrathalamica (ZLI), a narrow compartment in the vertebrate forebrain that bisects the diencephalon transversely, expresses the secreted factor sonic hedgehog (Shh). Because genetic disruption ofShh in mouse causes severe early developmental defects, this strategy has not been useful in identifying a ZLI-specific role for this gene. To modulate Shh signaling in a spatiotemporally restricted manner, we carried out gain- and loss-of-function experiments in chick embryos usingin ovo electroporation and found that Shh signaling is required for region-specific gene expression in thalamus and prethalamus, the major diencephalic brain areas flanking the ZLI. We further show that differential competence of thalamic and prethalamic primordia in responding to Shh signaling is regulated by the transcription factor Irx3. We show that, through the release of Shh, the ZLI functions as a local signaling center that regulates the acquisition of identity for these important diencephalic regions.

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Figure 1: Schematic illustration of embryonic chick brain.
Figure 2: Gene expression in the diencephalon at definitive ZLI stages.
Figure 3: Overexpression of Shh results in expansion of thalamus and prethalamus.
Figure 4: A requirement for Shh signaling in prethalamus and thalamus.
Figure 5: Shh signaling is required for ZLI-specific gene expression.
Figure 6: A 'dorsal truncation' of the ZLI results in a reducedGbx2 expression domain.
Figure 7: Ectopic Irx3 induces thalamic gene expression in the prethalamus.
Figure 8: Ectopic Irx3 induces thalamic gene expression in the prethalamus autonomously and in a Shh-dependent manner.

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Acknowledgements

We thank J. Briscoe, J. Dodd, J. Gilthorpe, M. Goulding, M. Hargrave, A. Leutz, T. Ogura, C. Ragsdale, J. Rubenstein, A. Ruiz i Altaba, F. Schubert and C. Tabin for generously providing reagents and J. Gilthorpe, R. Wingate and other members of our laboratory for constructive criticism on the manuscript. This work was supported by the UK Medical Research Council and the Wellcome Trust.

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Authors and Affiliations

  1. MRC Centre for Developmental Neurobiology, 4th Floor, New Hunt's House, Guy's Hospital Campus, King's College, London, SE1 1UL, UK

    Clemens Kiecker & Andrew Lumsden

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  1. Clemens Kiecker
  2. Andrew Lumsden

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Correspondence toAndrew Lumsden.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Schematic representation of the role of Shh signalling from the ZLI in thalamic and prethalamic development. Regional gene expression is represented in the same colours as inFig. 1. (PDF 99 kb)

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Kiecker, C., Lumsden, A. Hedgehog signaling from the ZLI regulates diencephalic regional identity.Nat Neurosci7, 1242–1249 (2004). https://doi.org/10.1038/nn1338

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