Editors' ChoiceDevelopmental Biology

Defining Boundaries with Notch

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Science Signaling  16 Aug 2011:
Vol. 4, Issue 186, pp. ec229
DOI: 10.1126/scisignal.4186ec229

Compartment boundaries separate adjacent populations of cells and prevent them from mixing. Notch signaling is important for maintaining some compartment boundaries, notably in the imaginal discs of fruit fly wings and in the vertebrate central nervous system. The dorsoventral (DV) compartment boundary of the imaginal disc contains an actomyosin barrier and a zone of nonproliferating cells (ZNC), both of which are thought to inhibit cell mixing across the boundary. The actomyosin barrier includes F-actin, the actin polymerization factor Enabled (Ena), and the myosin II regulatory light chain Spaghetti Squash (Sqh), which accumulate at the interface between boundary and nonboundary cells. Notch signaling along this compartment boundary defines the ZNC, but the mechanism connecting Notch signaling to boundary maintenance has not been elucidated. Becam et al. report that Notch-mediated repression of the microRNA bantam at the DV compartment boundary has a twofold effect on boundary stability. First, bantam promotes cell cycle progression; second, bantam inhibits Ena. Using a green fluorescent protein (GFP) reporter that is repressed by bantam, the authors demonstrated that bantam activity in the boundary cells increased in the absence of Notch. Ectopic expression of bantam throughout the wing pouch disrupted the DV boundary without affecting the anteroposterior (AP) boundary, which is not established or maintained by Notch. Reducing the abundance of Notch or ectopically expressing bantam induced the proliferation of boundary cells and compromised the smoothness of the boundary. The 3′ untranslated region (UTR) of ena contains a putative bantam target site, and overexpression of bantam reduced the abundance of Ena, whereas the abundance of Ena increased in clones of cells lacking bantam. Mutating or deleting the bantam binding sites in an ena 3′UTR sensor transgene resulted in uniform expression of the transgene across the wing pouch and rendered the transgene insensitive to bantam overexpression. Overexpression of bantam prevented the accumulation of F-actin at the DV compartment boundary, as did expression of ena double-stranded RNA (dsRNA), which also caused the boundary to be irregularly shaped. These results suggest that one mechanism through which Notch signaling maintains the DV compartment boundary is by repressing expression of bantam, thereby inhibiting cell proliferation and contributing to formation of the actomyosin structure that defines the boundary.

I. Becam, N. Rafel, X. Hong, S. M. Cohen, M. Milán, Notch-mediated repression of bantam miRNA contributes to boundary formation in the Drosophila wing. Development 138, 3781–3789 (2011). [Abstract] [Full Text]

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