TY - JOUR
T1 - A network of broadly expressed hlh genes regulates tissue-specific cell fates
AU - Bhattacharya, Abhishek
AU - Baker, Nicholas E.
N1 - Funding Information:
This work was enabled by the gift of polyclonal anti-Emc antibody by Yuh-Nung Jan. We also thank Claire Cronmiller for monoclonal anti-Da antibody, Konrad Basler and Christos Delidakis for strains and other reagents, Matthew Scharff and Richard Chahwan for help with HEK293T cell culture, Model System Genomics for embryo injections, John Fullard and David Lubensky for advice, and Hannes Buelow, Claude Desplan, Scott Emmons, Andreas Jenny, Richard Mann, Ertugrul Ozbudak, Julie Secombe, Jessica Treisman, and Lan-Hsin Wang for comments on the manuscript. This work was supported by grant GM47892 from the NIH and by an Unrestricted Grant from Research to Prevent Blindness to the Department of Ophthalmology and Visual Sciences. Confocal microscopy was performed at the AIF, AECOM. Data in this paper are from a thesis to be submitted in partial fulfillment of the requirement for the degree of Doctor of Philosophy in the Graduate Division of Biomedical Sciences, Albert Einstein College of Medicine, Yeshiva University, USA.
PY - 2011/11/11
Y1 - 2011/11/11
N2 - Spatial and temporal expression of specific basic-helix-loop-helix (bHLH) transcription factors defines many types of cellular differentiation. We find that a distinct mechanism regulates the much broader expression of the heterodimer partners of these specific factors and impinges on differentiation. In Drosophila, a cross-interacting regulatory network links expression of the E protein Daughterless (Da), which heterodimerizes with bHLH proteins to activate them, with expression of the Id protein Extramacrochaetae (Emc), which antagonizes bHLH proteins. Coupled transcriptional feedback loops maintain the widespread Emc expression that restrains Da expression, opposing bHLH-dependent differentiation while enhancing growth and cell survival. Where extracellular signals repress emc, Da expression can increase. This defines regions of proneural ectoderm independently from the proneural bHLH genes. Similar regulation is found in multiple Drosophila tissues and in mammalian cells and therefore is likely to be a conserved general feature of developmental regulation by HLH proteins.
AB - Spatial and temporal expression of specific basic-helix-loop-helix (bHLH) transcription factors defines many types of cellular differentiation. We find that a distinct mechanism regulates the much broader expression of the heterodimer partners of these specific factors and impinges on differentiation. In Drosophila, a cross-interacting regulatory network links expression of the E protein Daughterless (Da), which heterodimerizes with bHLH proteins to activate them, with expression of the Id protein Extramacrochaetae (Emc), which antagonizes bHLH proteins. Coupled transcriptional feedback loops maintain the widespread Emc expression that restrains Da expression, opposing bHLH-dependent differentiation while enhancing growth and cell survival. Where extracellular signals repress emc, Da expression can increase. This defines regions of proneural ectoderm independently from the proneural bHLH genes. Similar regulation is found in multiple Drosophila tissues and in mammalian cells and therefore is likely to be a conserved general feature of developmental regulation by HLH proteins.
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U2 - 10.1016/j.cell.2011.08.055
DO - 10.1016/j.cell.2011.08.055
M3 - Article
C2 - 22078884
AN - SCOPUS:81055144810
SN - 0092-8674
VL - 147
SP - 881
EP - 892
JO - Cell
JF - Cell
IS - 4
ER -