Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and hedgehog signaling

Murielle Rallu, Robert Machold, Nicholas Gaiano, Joshua G. Corbin, Andrew P. McMahon, Gordon Fishell

    Research output: Contribution to journalArticle

    Abstract

    Considerable data suggest that sonic hedgehog (Shh) is both necessary and sufficient for the specification of ventral pattern throughout the nervous system, including the telencephalon. We show that the regional markers induced by Shh in the E9.0 telencephalon are dependent on the dorsoventral and anteroposterior position of ectopic Shh expression. This suggests that by this point in development regional character in the telencephalon is established. To determine whether this prepattern is dependent on earlier Shh signaling, we examined the telencephalon in mice carrying either Shh- or Gli3-null mutant alleles. This analysis revealed that the expression of a subset of ventral telencephalic markers, including Dlx2 and Gsh2, although greatly diminished, persist in Shh-/- mutants, and that these same markers were expanded in Gli3-/- mutants. To understand further the genetic interaction between Shh and Gli3, we examined Shh/Gli3 and Smoothened/Gli3 double homozygous mutants. Notably, in animals carrying either of these genetic backgrounds, genes such as Gsh2 and Dlx2, which are expressed pan-ventrally, as well as Nkx2.1, which demarcates the ventral most aspect of the telencephalon, appear to be largely restored to their wild-type patterns of expression. These results suggest that normal patterning in the telencephalon depends on the ventral repression of Gli3 function by Shh and, conversely, on the dorsal repression of Shh signaling by Gli3. In addition these results support the idea that, in addition to hedgehog signaling, a Shh-independent pathways must act during development to pattern the telencephalon.

    Original languageEnglish (US)
    Pages (from-to)4963-4974
    Number of pages12
    JournalDevelopment
    Volume129
    Issue number21
    StatePublished - Jan 1 2002

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    Telencephalon
    Hedgehogs
    Nervous System

    Keywords

    • Gli3
    • Mouse
    • Shh
    • Telencephalon

    ASJC Scopus subject areas

    • Anatomy
    • Cell Biology

    Cite this

    Rallu, M., Machold, R., Gaiano, N., Corbin, J. G., McMahon, A. P., & Fishell, G. (2002). Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and hedgehog signaling. Development, 129(21), 4963-4974.

    Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and hedgehog signaling. / Rallu, Murielle; Machold, Robert; Gaiano, Nicholas; Corbin, Joshua G.; McMahon, Andrew P.; Fishell, Gordon.

    In: Development, Vol. 129, No. 21, 01.01.2002, p. 4963-4974.

    Research output: Contribution to journalArticle

    Rallu, M, Machold, R, Gaiano, N, Corbin, JG, McMahon, AP & Fishell, G 2002, 'Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and hedgehog signaling', Development, vol. 129, no. 21, pp. 4963-4974.
    Rallu M, Machold R, Gaiano N, Corbin JG, McMahon AP, Fishell G. Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and hedgehog signaling. Development. 2002 Jan 1;129(21):4963-4974.
    Rallu, Murielle ; Machold, Robert ; Gaiano, Nicholas ; Corbin, Joshua G. ; McMahon, Andrew P. ; Fishell, Gordon. / Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and hedgehog signaling. In: Development. 2002 ; Vol. 129, No. 21. pp. 4963-4974.
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    AU - Machold, Robert

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    AU - Corbin, Joshua G.

    AU - McMahon, Andrew P.

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    AB - Considerable data suggest that sonic hedgehog (Shh) is both necessary and sufficient for the specification of ventral pattern throughout the nervous system, including the telencephalon. We show that the regional markers induced by Shh in the E9.0 telencephalon are dependent on the dorsoventral and anteroposterior position of ectopic Shh expression. This suggests that by this point in development regional character in the telencephalon is established. To determine whether this prepattern is dependent on earlier Shh signaling, we examined the telencephalon in mice carrying either Shh- or Gli3-null mutant alleles. This analysis revealed that the expression of a subset of ventral telencephalic markers, including Dlx2 and Gsh2, although greatly diminished, persist in Shh-/- mutants, and that these same markers were expanded in Gli3-/- mutants. To understand further the genetic interaction between Shh and Gli3, we examined Shh/Gli3 and Smoothened/Gli3 double homozygous mutants. Notably, in animals carrying either of these genetic backgrounds, genes such as Gsh2 and Dlx2, which are expressed pan-ventrally, as well as Nkx2.1, which demarcates the ventral most aspect of the telencephalon, appear to be largely restored to their wild-type patterns of expression. These results suggest that normal patterning in the telencephalon depends on the ventral repression of Gli3 function by Shh and, conversely, on the dorsal repression of Shh signaling by Gli3. In addition these results support the idea that, in addition to hedgehog signaling, a Shh-independent pathways must act during development to pattern the telencephalon.

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