Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway
Version of Record online: 12 OCT 2005
Copyright © 2005 Wiley-Liss, Inc.
Volume 234, Issue 4, pages 922–933, December 2005
How to Cite
Jerome-Majewska, L. A., Jenkins, G. P., Ernstoff, E., Zindy, F., Sherr, C. J. and Papaioannou, V. E. (2005), Tbx3, the ulnar-mammary syndrome gene, and Tbx2 interact in mammary gland development through a p19Arf/p53-independent pathway. Dev. Dyn., 234: 922–933. doi: 10.1002/dvdy.20575
- Issue online: 16 NOV 2005
- Version of Record online: 12 OCT 2005
- Manuscript Accepted: 4 AUG 2005
- Manuscript Revised: 1 AUG 2005
- Manuscript Received: 6 MAY 2005
- NIH. Grant Number: RO1 HD033082
- ulnar-mammary syndrome;
- mammary gland induction
The closely related T-box genes Tbx2 and Tbx3 are both expressed in the developing mammary glands of mouse embryos and both have been implicated in mammary carcinogenesis. Tbx3 is essential for induction of the mammary placodes in mice. In humans, mutations in TBX3 are responsible for ulnar-mammary syndrome. Here, we show a haploinsufficiency effect of Tbx3 on maintenance of the mammary placodes and on the extent of branching of the ductal tree in mice. Loss or heterozygosity for Tbx2, on the other hand, has no effect on either induction or maintenance of the placodes, although a small effect was seen on branching morphogenesis in adult heterozygotes. However, the deficiency in maintenance of the mammary placodes in Tbx2, Tbx3 double heterozygous mice is more marked than in Tbx3 single heterozygotes, indicating a genetic interaction between the two genes. In spite of a large body of evidence implicating these genes in cell cycle control through the p19Arf/p53 pathways, we find no evidence for involvement of these pathways either in embryonic lethality of homozygous mutants or in the mammary gland phenotype of Tbx3 heterozygous mice. Developmental Dynamics 234:922–933, 2005. © 2005 Wiley-Liss, Inc.