TY - JOUR
T1 - Regulation of Cell Adhesion and Collective Cell Migration by Hindsight and Its Human Homolog RREB1
AU - Melani, Mariana
AU - Simpson, Kaylene J.
AU - Brugge, Joan S.
AU - Montell, Denise
N1 - Funding Information:
We thank members of the fly community for reagents as listed on the text. We thank members of Denise Montell lab, especially Michelle Starz-Gaiano for helpful comments and discussion and Mohit Prasad for help with live-imaging studies. We acknowledge James Bui for technical help. Thanks to Enrique Martin-Blanco for sharing unpublished data. The project described was supported by the Cell Migration Consortium Grant Number U54 GM064346, the Department of Defense (W81XWH-04-1-0360), and R01 GM73164 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health.
PY - 2008/4/8
Y1 - 2008/4/8
N2 - Cell movements represent a major driving force in embryonic development, tissue repair, and tumor metastasis [1]. The migration of single cells has been well studied, predominantly in cell culture [2, 3]; however, in vivo, a greater variety of modes of cell movement occur, including the movements of cells in clusters, strands, sheets, and tubes, also known as collective cell migrations [4, 5]. In spite of the relevance of these types of movements in both normal and pathological conditions, the molecular mechanisms that control them remain predominantly unknown. Epithelial follicle cells of the Drosophila ovary undergo several dynamic morphological changes, providing a genetically tractable model [6]. We found that anterior follicle cells, including border cells, mutant for the gene hindsight (hnt) accumulated excess cell-cell adhesion molecules and failed to undergo their normal collective movements. In addition, HNT affected border cell cluster cohesion and motility via effects on the JNK and STAT pathways, respectively. Interestingly, reduction of expression of the mammalian homolog of HNT, RREB1, by siRNA inhibited collective cell migration in a scratch-wound healing assay of MCF10A mammary epithelial cells, suppressed surface activity, retarded cell spreading after plating, and led to the formation of immobile, tightly adherent cell colonies. We propose that HNT and RREB1 are essential to reduce cell-cell adhesion when epithelial cells within an interconnected group undergo dynamic changes in cell shape.
AB - Cell movements represent a major driving force in embryonic development, tissue repair, and tumor metastasis [1]. The migration of single cells has been well studied, predominantly in cell culture [2, 3]; however, in vivo, a greater variety of modes of cell movement occur, including the movements of cells in clusters, strands, sheets, and tubes, also known as collective cell migrations [4, 5]. In spite of the relevance of these types of movements in both normal and pathological conditions, the molecular mechanisms that control them remain predominantly unknown. Epithelial follicle cells of the Drosophila ovary undergo several dynamic morphological changes, providing a genetically tractable model [6]. We found that anterior follicle cells, including border cells, mutant for the gene hindsight (hnt) accumulated excess cell-cell adhesion molecules and failed to undergo their normal collective movements. In addition, HNT affected border cell cluster cohesion and motility via effects on the JNK and STAT pathways, respectively. Interestingly, reduction of expression of the mammalian homolog of HNT, RREB1, by siRNA inhibited collective cell migration in a scratch-wound healing assay of MCF10A mammary epithelial cells, suppressed surface activity, retarded cell spreading after plating, and led to the formation of immobile, tightly adherent cell colonies. We propose that HNT and RREB1 are essential to reduce cell-cell adhesion when epithelial cells within an interconnected group undergo dynamic changes in cell shape.
KW - CELLBIO
KW - DEVBIO
KW - SIGNALING
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U2 - 10.1016/j.cub.2008.03.024
DO - 10.1016/j.cub.2008.03.024
M3 - Article
C2 - 18394891
AN - SCOPUS:41449086948
SN - 0960-9822
VL - 18
SP - 532
EP - 537
JO - Current Biology
JF - Current Biology
IS - 7
ER -