Molecular interactions between Tbx3 and Bmp4 and a model for dorsoventral positioning of mammary gland development.

The formation of the dorsoventral (DV) boundary is central to establishing the body plan in embryonic development. Although there is some information about how limbs are positioned along the DV axis and how DV skin color pattern is determined, the way in which mammary glands are positioned is unknown. Here we focus on Bmp4 and Tbx3, a gene associated with ulnar-mammary syndrome, and compare their expression along the DV axis in relation to mammary gland initiation in mouse embryos.

Negative feedback predominates over cross-regulation to control ERK MAPK activity in response to FGF signalling in embryos.

Expression of the gene encoding the MKP-3/Pyst1 protein phosphatase, which inactivates ERK MAPK, is induced by FGF. However, which intracellular signalling pathway mediates this expression is unclear, with essential roles proposed for both ERK and PI(3)K in chick embryonic limb. Here, we report that MKP-3/Pyst1 expression is sensitive to inhibition of ERK or MAPKK, that endogenous MKP-3/Pyst1 co-localizes with activated ERK, and expression of MKP-3/Pyst1 in mice lacking PDK1, an essential mediator of PI(3)K signalling.

Evidence that autocrine signaling through Bmpr1a regulates the proliferation, survival and morphogenetic behavior of distal lung epithelial cells.

Lung development requires reciprocal epithelial/mesenchymal interactions, mediated by signaling factors such as Bmps made in both cell populations. To address the role of Bmp signaling in the epithelium, we have exploited the fact that Bmp receptor type Ia (Alk3) is expressed in the epithelium during branching morphogenesis. Deletion of Bmpr1a in the epithelium with an Sftpc-cre transgene leads to dramatic defects in lung development.

Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos.

Interactions between Wnts, Fgfs and Tbx genes are involved in limb initiation and the same gene families have been implicated in mammary gland development. Here we explore how these genes act together in mammary gland initiation. We compared expression of Tbx3, the gene associated with the human condition ulnar-mammary syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by sensitivity to the SU5402 inhibitor), and expression of Lef1, encoding a transcription factor mediating Wnt signalling and the earliest gene so far known to be expressed in mammary gland development.

Negative feedback regulation of FGF signaling levels by Pyst1/MKP3 in chick embryos.

Background: The importance of endogenous antagonists in intracellular signal transduction pathways is becoming increasingly recognized. There is evidence in cultured mammalian cells that Pyst1/MKP3, a dual specificity protein phosphatase, specifically binds to and inactivates ERK1/2 mitogen-activated protein kinases (MAPKs). High-level Pyst1/Mkp3 expression has recently been found at many sites of known FGF signaling in mouse embryos, but the significance of this association and its function are not known.

Regulation of Tbx3 expression by anteroposterior signalling in vertebrate limb development.

Tbx3, a T-box gene family member related to the Drosophila gene optomotor blind (omb) and encoding a transcription factor, is expressed in anterior and posterior stripes in developing chick limb buds. Tbx3 haploinsufficiency has been linked with the human condition ulnar-mammary syndrome, in which predominantly posterior defects occur in the upper limb. Omb is expressed in Drosophila wing development in response to a signalling cascade involving Hedgehog and Dpp.

Expression of the ERK-specific MAP kinase phosphatase PYST1/MKP3 in mouse embryos during morphogenesis and early organogenesis.

Mitogen-activated-protein kinase (MAP kinase) cascades are effector mechanisms for many growth factor signals implicated in developmental processes, including appendage outgrowth and organogenesis. The cascade culminates in extracellular-signal-regulated MAP kinase (ERK), which enters the nucleus. ERK activity reflects the competing actions of upstream activator kinases and inhibitory MAP kinase phosphatases.