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The Zic family homologue Odd-paired regulates Alk expression in Drosophila.

Journal article
Authors Patricia Mendoza-García
Fredrik Hugosson
Mahsa Fallah
Michael L Higgins
Yasuno Iwasaki
Kathrin Pfeifer
Georg Wolfstetter
Gaurav Varshney
Dmitry Popichenko
J Peter Gergen
Korneel Hens
Bart Deplancke
Ruth H. Palmer
Published in PLoS genetics
Volume 13
Issue 4
ISSN 1553-7404
Publication year 2017
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Language en
Links dx.doi.org/10.1371/journal.pgen.100...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Biological Sciences

Abstract

The Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) plays a critical role in the specification of founder cells (FCs) in the Drosophila visceral mesoderm (VM) during embryogenesis. Reporter gene and CRISPR/Cas9 deletion analysis reveals enhancer regions in and upstream of the Alk locus that influence tissue-specific expression in the amnioserosa (AS), the VM and the epidermis. By performing high throughput yeast one-hybrid screens (Y1H) with a library of Drosophila transcription factors (TFs) we identify Odd-paired (Opa), the Drosophila homologue of the vertebrate Zic family of TFs, as a novel regulator of embryonic Alk expression. Further characterization identifies evolutionarily conserved Opa-binding cis-regulatory motifs in one of the Alk associated enhancer elements. Employing Alk reporter lines as well as CRISPR/Cas9-mediated removal of regulatory elements in the Alk locus, we show modulation of Alk expression by Opa in the embryonic AS, epidermis and VM. In addition, we identify enhancer elements that integrate input from additional TFs, such as Binou (Bin) and Bagpipe (Bap), to regulate VM expression of Alk in a combinatorial manner. Taken together, our data show that the Opa zinc finger TF is a novel regulator of embryonic Alk expression.

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