Neuregulin-3 regulates epithelial progenitor cell positioning and specifies mammary phenotype.

Mutation of Neuregulin-3 (Nrg3) results in defective embryonic mammary gland development. Here, we investigate functions of Nrg3 signaling in embryonic mammary morphogenesis. Nrg3 regulates the distribution of epithelial progenitor cells within the presumptive mammary-forming region during early mammary morphogenesis.

Cdk5 phosphorylation of ErbB4 is required for tangential migration of cortical interneurons.

Interneuron dysfunction in humans is often associated with neurological and psychiatric disorders, such as epilepsy, schizophrenia, and autism. Some of these disorders are believed to emerge during brain formation, at the time of interneuron specification, migration, and synapse formation. Here, using a mouse model and a host of histological and molecular biological techniques, we report that the signaling molecule cyclin-dependent kinase 5 (Cdk5), and its activator p35, control the tangential migration of interneurons toward and within the cerebral cortex by modulating the critical neurodevelopmental signaling pathway, ErbB4/phosphatidylinositol 3-kinase, that has been repeatedly linked to schizophrenia.

Embryonic mammary signature subsets are activated in Brca1-/- and basal-like breast cancers.

Introduction: Cancer is often suggested to result from development gone awry. Links between normal embryonic development and cancer biology have been postulated, but no defined genetic basis has been established. We recently published the first transcriptomic analysis of embryonic mammary cell populations.

Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment.

Introduction: The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simple epithelium even across species and classes, and can partially restore features of differentiated tissue to mouse mammary tumours in co-culture experiments.

The ERalpha coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium.

The HER4 intracellular domain (4ICD) is a potent estrogen receptor (ERalpha) coactivator with activities in breast cancer and the developing mammary gland that appear to overlap with progesterone receptor (PgR). In fact, 4ICD has recently emerged as an important regulator and predictor of tamoxifen response, a role previously thought to be fulfilled by PgR. Here we investigated the possibility that the 4ICD coactivator regulates PgR expression thereby providing a mechanistic explanation for their partially overlapping activities in breast cancer.

Embryonic mammary anlagen analysis using immunolabelling of whole mounts.

The mouse mammary gland is a unique organ since although the mammary gland primordium forms during embryogenesis, the majority of development occurs postnatally upon hormonal stimulation at puberty and full functionality (i.e. lactation) is not achieved until after parturition.

Dynamic expression of Erbb pathway members during early mammary gland morphogenesis.

Similar to other epithelial appendages, mammary anlagen progress from stratified epithelium through placode and bud stages. Embryonic mammary morphogenesis is elicited by a combination of local cell migration, adhesion changes and proliferation, and these same developmental processes impact breast cancer etiology. The Erbb signaling network plays important roles in postnatal mammary gland morphogenesis and carcinogenesis.

Neuregulin3 alters cell fate in the epidermis and mammary gland.

Background: The Neuregulin family of ligands and their receptors, the Erbb tyrosine kinases, have important roles in epidermal and mammary gland development as well as during carcinogenesis. Previously, we demonstrated that Neuregulin3 (Nrg3) is a specification signal for mammary placode formation in mice. Nrg3 is a growth factor, which binds and activates Erbb4, a receptor tyrosine kinase that regulates cell proliferation and differentiation.