The Tlx-2 homeobox gene is a downstream target of BMP signalling and is required for mouse mesoderm development.
TGFbeta-related factors are critical regulators of vertebrate mesoderm development. However, the signalling cascades required for their function during this developmental process are poorly defined. Tlx-2 is a homeobox gene expressed in the primitive streak of mouse embryos. Exogenous BMP-2 rapidly activates Tlx-2 expression in the epiblast of E6.5 embryos. A Tlx-2 promoter element responds to BMP-2 signals in P19 cells, and this response is mediated by BMP type I receptors and Smad1. These results suggest that Tlx-2 is a downstream target gene for BMP signalling in the primitive streak where BMP-4 and other TGFbeta-related factors are expressed. Furthermore, disruption of Tlx-2 function leads to early embryonic lethality. Similar to BMP4 and ALK3 mutants, the mutant embryos display severe defects in primitive streak and mesoderm formation. These experiments thus define a BMP/Tlx-2 signalling pathway that is required during early mammalian gastrulation.
Tang
S J
SJ
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
Hoodless
P A
PA
Lu
Z
Z
Breitman
M L
ML
McInnes
R R
RR
Wrana
J L
JL
Buchwald
M
M
D029404:Activin Receptors; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005801:Genes, Homeobox / Q000502:physiology*; D008648:Mesoderm; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D017978:Receptors, Growth Factor / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D029404:Activin Receptors; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I