Hox genes regulate the onset of Tbx5 expression in the forelimb

Carolina Minguillon*, Satoko Nishimoto, Sophie Wood, Elisenda Vendrell, Jeremy J. Gibson-Brown, Malcolm P.O. Logan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)

Abstract

Tbx4 and Tbx5 are two closely related T-box genes that encode transcription factors expressed in the prospective hindlimb and forelimb territories, respectively, of all jawed vertebrates. Despite their striking limb type-restricted expression pattern, we have shown that these genes do not participate in the acquisition of limb type-specific morphologies. Instead, Tbx4 and Tbx5 play similar roles in the initiation of hindlimb and forelimb outgrowth, respectively. We hypothesized that different combinations of Hox proteins expressed in different rostral and caudal domains of the lateral plate mesoderm, where limb induction occurs, might be involved in regulating the limb type-restricted expression of Tbx4 and Tbx5 and in the later determination of limb type-specific morphologies. Here, we identify the minimal regulatory element sufficient for the earliest forelimb-restricted expression of the mouse Tbx5 gene and show that this sequence is Hox responsive. Our results support a mechanism in which Hox genes act upstream of Tbx5 to control the axial position of forelimb formation.

Original languageEnglish
Pages (from-to)3180-3188
Number of pages9
JournalDevelopment
Volume139
Issue number17
DOIs
Publication statusPublished - 1 Sept 2012

Keywords

  • Tbx5
  • Hox
  • Limb development
  • T-BOX GENES
  • VERTEBRATE LIMB SPECIFICATION
  • HOMEOTIC TRANSFORMATIONS
  • TRANSCRIPTION FACTORS
  • MOUSE EMBRYO
  • CHICK-EMBRYO
  • MUTANT MICE
  • IDENTITY
  • EVOLUTION
  • OUTGROWTH

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