Lindsay Hinck

Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein c...

Published in The Journal of Cell Biology

Wnt-1 homologs have been identified in invertebrates and vertebrates and play important roles in cellular differentiation and organization. In Drosophila, the products of the segment polarity genes wingless (the Wnt-1 homolog) and armadillo participate in a signal transduction pathway important for cellular boundary formation in embryonic developme...

SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number.

Published in Developmental Cell

In the field of breast biology, there is a growing appreciation for the "gatekeeping function" of basal cells during development and disease processes yet mechanisms regulating the generation of these cells are poorly understood. Here, we report that the proliferation of basal cells is controlled by SLIT/ROBO1 signaling and that production of these...

The versatile roles of "axon guidance" cues in tissue morphogenesis.

Published in Developmental Cell

The Netrin, Slit, Semaphorin, and Ephrin families of secreted proteins were originally characterized in the nervous system as guidance cues for axons; however, recent studies demonstrate that many members of these families contribute to the development of a variety of organs. Here, the current knowledge of their roles is discussed with a focus on f...

Netrin-1/neogenin interaction stabilizes multipotent progenitor cap cells during mammary gland morphogenesis.

Published in Developmental Cell

Netrin-1 and its receptors play an essential role patterning the nervous system by guiding neurons and axons to their targets. To explore whether netrin-1 organizes nonneural tissues, we examined its role in mammary gland morphogenesis. Netrin-1 is expressed in prelumenal cells, and its receptor neogenin is expressed in a complementary pattern in a...

Guidance of developing axons by netrin-1 and its receptors.

Published in Cold Spring Harbor Symposia on Quantitative Biology

Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors.

Published in Nature

In the developing nervous system, migrating cells and axons are guided to their targets by cues in the extracellular environment. The netrins are a family of phylogenetically conserved guidance cues that can function as diffusible attractants and repellents for different classes of cells and axons. In vertebrates, insects and nematodes, members of ...

Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells.

Published in The Journal of Cell Biology

The cadherin/catenin complex plays important roles in cell adhesion, signal transduction, as well as the initiation and maintenance of structural and functional organization of cells and tissues. In the preceding study, we showed that the assembly of the cadherin/catenin complex is temporally regulated, and that novel combinations of catenin and ca...

Navigating breast cancer: axon guidance molecules as breast cancer tumor suppressors and oncogenes.

Published in Journal of Mammary Gland Biology and Neoplasia

Slit, Netrin, Ephrin, and Semaphorin s roles in development have expanded greatly in the past decade from their original characterization as axon guidance molecules (AGMs) to include roles as regulators of tissue morphogenesis and development in diverse organs. In the mammary gland, AGMs are important for maintaining normal cell proliferation and a...

Guidance of developing axons by netrin-1 and its receptors.

Published in Cold Spring Harbor Symposia on Quantitative Biology

Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells.

Published in The Journal of Cell Biology

The cadherin/catenin complex plays important roles in cell adhesion, signal transduction, as well as the initiation and maintenance of structural and functional organization of cells and tissues. In the preceding study, we showed that the assembly of the cadherin/catenin complex is temporally regulated, and that novel combinations of catenin and ca...

Properties of Wnt-1 protein that enable cell surface association.

Published in Oncogene

Members of the highly conserved Wnt gene family serve key functions in cellular growth and differentiation. Regulated expression of the murine Wnt-1 proto-oncogene is essential for normal development of the embryonic nervous system and when misexpressed in the mammary gland leads to hyperplasias and tumorigenic progression. Wnt-1 encodes a cysteine...

Reduced expression of AP27 protein, the product of a growth factor-repressible gene, is associated with diminished adipo...

Published in Proceedings of the National Academy of Sciences

We have recently characterized an adipocyte cDNA (clone 5) that is enhanced in expression by environmental and hormonal conditions favoring adipogenic differentiation. Moreover, certain agents including fibroblast growth factor and phorbol 12-myristate 13-acetate (but not epidermal growth factor) markedly inhibit clone 5 gene expression and prevent...

Discrimination of DNA response elements for thyroid hormone and estrogen is dependent on dimerization of receptor DNA bi...

Published in Proceedings of the National Academy of Sciences

We and others have previously shown that a two-amino acid substitution in the base of the first zinc finger of the glucocorticoid receptor DNA binding domain (DBD) is sufficient to alter the receptor s target DNA from a glucocorticoid response element (GRE) to an estrogen response element (ERE). Activation of a thyroid hormone response element (TRE...

Protein interacting with C-kinase 1/protein kinase Calpha-mediated endocytosis converts netrin-1-mediated repulsion to a...

Published in Journal of Neuroscience

In vertebrates, the receptor families deleted in colorectal cancer (DCC) and UNC5 mediate responses to the bifunctional guidance cue netrin-1. DCC mediates attraction, whereas a complex of DCC and UNC5 mediates repulsion. Thus, a primary determinant of the responsiveness of an axon to netrin-1 is the presence or absence of UNC5 family members on th...

Key stages in mammary gland development: the mammary end bud as a motile organ.

Published in Breast Cancer Research

In the rodent, epithelial end buds define the tips of elongating mammary ducts. These highly motile structures undergo repeated dichotomous branching as they aggressively advance through fatty stroma and, turning to avoid other ducts, they finally cease growth leaving behind the open, tree-like framework on which secretory alveoli develop during pr...

UNC5C is required for spinal accessory motor neuron development.

Published in Molecular and Cellular Neuroscience

In both invertebrates and vertebrates, UNC5 receptors facilitate chemorepulsion away from a Netrin source. Unlike most motor neurons in the embryonic vertebrate spinal cord, spinal accessory motor neuron (SACMN) cell bodies and their axons translocate along a dorsally directed trajectory away from the floor plate/ventral midline and toward the late...

The versatile roles of "axon guidance" cues in tissue morphogenesis.

Published in Developmental Cell

The Netrin, Slit, Semaphorin, and Ephrin families of secreted proteins were originally characterized in the nervous system as guidance cues for axons; however, recent studies demonstrate that many members of these families contribute to the development of a variety of organs. Here, the current knowledge of their roles is discussed with a focus on f...

Changes in cell and tissue organization in cancer of the breast and colon.

Published in Current Opinion in Cell Biology

Most cancers arise in epithelia, the tissue type that lines all body cavities. The organization of epithelia enables them to act as a barrier and perform vectorial transport of molecules between body compartments. Crucial for their organization and function is a highly specialized network of cell adhesion and polarity proteins aligned along the api...

Vascular Robo4 restricts proangiogenic VEGF signaling in breast.

Published in Proceedings of the National Academy of Sciences

Formation of the vascular system within organs requires the balanced action of numerous positive and negative factors secreted by stromal and epithelial cells. Here, we used a genetic approach to determine the role of SLITs in regulating the growth and organization of blood vessels in the mammary gland. We demonstrate that vascularization of the gl...

Robo4 cooperates with CXCR4 to specify hematopoietic stem cell localization to bone marrow niches.

Published in Cell Stem Cell

Specific bone marrow (BM) niches are critical for hematopoietic stem cell (HSC) function during both normal hematopoiesis and in stem cell transplantation therapy. We demonstrate that the guidance molecule Robo4 functions to specifically anchor HSCs to BM niches. Robo4-deficient HSCs displayed poor localization to BM niches and drastically reduced ...