Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development

Edwina McGlinn, Kelly van Bueren, Salvatore Fiorenza, Rong Mo, Alisa Poh, Alastair Forrest, Marcelo Soares, Maria de Fatima Bonaldo, Sean Grimmond, Chi-Chung Hui, Brandon Wainwright, Carol Wicking

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Abstract

From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt) limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits.
Original languageEnglish
Pages (from-to)1218 - 1233
Number of pages16
JournalMechanisms of Development
Volume122
Issue number11
DOIs
Publication statusPublished - 2005
Externally publishedYes

Cite this

McGlinn, E., van Bueren, K., Fiorenza, S., Mo, R., Poh, A., Forrest, A., ... Wicking, C. (2005). Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development. Mechanisms of Development, 122(11), 1218 - 1233. https://doi.org/10.1016/j.mod.2005.06.012
McGlinn, Edwina ; van Bueren, Kelly ; Fiorenza, Salvatore ; Mo, Rong ; Poh, Alisa ; Forrest, Alastair ; Soares, Marcelo ; Bonaldo, Maria de Fatima ; Grimmond, Sean ; Hui, Chi-Chung ; Wainwright, Brandon ; Wicking, Carol. / Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development. In: Mechanisms of Development. 2005 ; Vol. 122, No. 11. pp. 1218 - 1233.
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title = "Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development",
abstract = "From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt) limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits.",
author = "Edwina McGlinn and {van Bueren}, Kelly and Salvatore Fiorenza and Rong Mo and Alisa Poh and Alastair Forrest and Marcelo Soares and Bonaldo, {Maria de Fatima} and Sean Grimmond and Chi-Chung Hui and Brandon Wainwright and Carol Wicking",
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McGlinn, E, van Bueren, K, Fiorenza, S, Mo, R, Poh, A, Forrest, A, Soares, M, Bonaldo, MDF, Grimmond, S, Hui, C-C, Wainwright, B & Wicking, C 2005, 'Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development', Mechanisms of Development, vol. 122, no. 11, pp. 1218 - 1233. https://doi.org/10.1016/j.mod.2005.06.012

Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development. / McGlinn, Edwina; van Bueren, Kelly; Fiorenza, Salvatore; Mo, Rong; Poh, Alisa; Forrest, Alastair; Soares, Marcelo; Bonaldo, Maria de Fatima; Grimmond, Sean; Hui, Chi-Chung; Wainwright, Brandon; Wicking, Carol.

In: Mechanisms of Development, Vol. 122, No. 11, 2005, p. 1218 - 1233.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Pax9 and Jagged1 act downstream of Gli3 in vertebrate limb development

AU - McGlinn, Edwina

AU - van Bueren, Kelly

AU - Fiorenza, Salvatore

AU - Mo, Rong

AU - Poh, Alisa

AU - Forrest, Alastair

AU - Soares, Marcelo

AU - Bonaldo, Maria de Fatima

AU - Grimmond, Sean

AU - Hui, Chi-Chung

AU - Wainwright, Brandon

AU - Wicking, Carol

PY - 2005

Y1 - 2005

N2 - From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt) limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits.

AB - From early in limb development the transcription factor Gli3 acts to define boundaries of gene expression along the anterior-posterior (AP) axis, establishing asymmetric patterns required to provide positional information. As limb development proceeds, posterior mesenchyme expression of Sonic hedgehog (Shh) regulates Gli3 transcription and post-translational processing to specify digit number and identity. The molecular cascades dependent on Gli3 at later stages of limb development, which link early patterning events with final digit morphogenesis, remain poorly characterised. By analysing the transcriptional consequences of loss of Gli3 in the anterior margin of the E11.5 and E12.5 limb bud in the polydactylous mouse mutant extra-toes (Gli3(Xt/Xt)), we have identified a number of known and novel transcripts dependent on Gli3 in the limb. In particular, we demonstrated that the genes encoding the paired box transcription factor Pax9, the Notch ligand Jagged1 and the cell surface receptor Cdo are dependent on Gli3 for correct expression in the anterior limb mesenchyme. Analysis of expression in compound Shh;Gli3 mutant mouse embryos and in both in vitro and in vivo Shh signaling assays, further defined the importance of Shh regulated processing of Gli3 in controlling gene expression. In particular Pax9 regulation by Shh and Gli3 was shown to be context dependent, with major differences between the limb and somite revealed by Shh bead implantation experiments in the chick. Jagged1 was shown to be induced by Shh in the chick limb and in a C3H10T1/2 cell based signaling assay, with Shh;Gli3 mutant analysis indicating that expression is dependent on Gli3 derepression. Our data have also revealed that perturbation of early patterning events within the Gli3(Xt/Xt) limb culminates in a specific delay of anterior chondrogenesis which is subsequently realised as extra digits.

UR - http://www.ncbi.nlm.nih.gov/pubmed/16169709

U2 - 10.1016/j.mod.2005.06.012

DO - 10.1016/j.mod.2005.06.012

M3 - Article

VL - 122

SP - 1218

EP - 1233

JO - Mechanisms of Development

JF - Mechanisms of Development

SN - 0925-4773

IS - 11

ER -