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The co-regulator dNAB interacts with Brinker to eliminate cells with reduced Dpp signaling.pdf (3.69 MB)

The co-regulator dNAB interacts with Brinker to eliminate cells with reduced Dpp signaling

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journal contribution
posted on 18.01.2021, 02:14 by O Ziv, Y Suissa, H Neuman, T Dinur, P Geuking, C Rhiner, Marta Portela-Esteban, F Lolo, E Moreno, O Gerlitz
The proper development of tissues requires morphogen activity that dictates the appropriate growth and differentiation of each cell according to its position within a developing field. Elimination of underperforming cells that are less efficient in receiving/transducing the morphogenetic signal is thought to provide a general fail-safe mechanism to avoid developmental misspecification. In the developing Drosophila wing, the morphogen Dpp provides cells with growth and survival cues. Much of the regulation of transcriptional output by Dpp is mediated through repression of the transcriptional repressor Brinker (Brk), and thus through the activation of target genes. Mutant cells impaired for Dpp reception or transduction are lost from the wing epithelium. At the molecular level, reduced Dpp signaling results in Brk upregulation that triggers apoptosis through activation of the JNK pathway. Here we show that the transcriptional co-regulator dNAB is a Dpp target in the developing wing that interacts with Brk to eliminate cells with reduced Dpp signaling through the JNK pathway. We further show that both dNAB and Brk are required for cell elimination induced by differential dMyc expression, a process that depends on reduced Dpp transduction in outcompeted cells.We propose a novel mechanism whereby the morphogen Dpp regulates the responsiveness to its own survival signal by inversely controlling the expression of a repressor, Brk, and its co-repressor, dNAB.

Funding

We thank K. Basler, Z. Paroush, L. Luo, G. Campbell, S. X. Hou, J. Diaz-Benjumea, A. Salzberg, G. Morata, The Vienna Drosophila RNAi Center and The Bloomington Drosophila Stock Center for fly stocks and antibodies; O. Spiegel for statistical analysis; and K. Basler, B. Shilo, Z. Paroush, R. Goldstein and E. Ordan for insightful discussions and comments on the manuscript. The authors declare that they have no competing financial interests. This research was supported by grants from the Israel Science Foundation (869/04), Israel Cancer Research Foundation and Abisch-Frenkel Foundation (0304624).

History

Publication Date

01/04/2009

Journal

Development

Volume

136

Issue

7

Pagination

(p. 1137-1145)

Publisher

COMPANY BIOLOGISTS LTD

ISSN

0950-1991

Rights Statement

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