DamID transcriptional profiling identifies the Snail/Scratch transcription factor Kahuli as an Alk target in the Drosophila visceral mesoderm

Author:

Mendoza-Garcia Patricia1ORCID,Basu Swaraj1ORCID,Sukumar Sanjay Kumar1ORCID,Arefin Badrul1,Wolfstetter Georg1,Anthonydhason Vimala1,Molander Linnea1,Uçkun Ezgi1,Lindehell Henrik2,Lebrero-Fernandez Cristina3,Larsson Jan2ORCID,Larsson Erik1,Bemark Mats34ORCID,Palmer Ruth H.1ORCID

Affiliation:

1. Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, SE-405 30 Gothenburg, Sweden

2. Department of Molecular Biology, Umeå University, SE-901 87 Umeå, Sweden

3. Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, SE-405 30 Gothenburg, Sweden

4. Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Region Västra Götaland, SE-41346 Gothenburg, Sweden

Abstract

ABSTRACT Development of the Drosophila visceral muscle depends on Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) signaling, which specifies founder cells (FCs) in the circular visceral mesoderm (VM). Although Alk activation by its ligand Jelly Belly (Jeb) is well characterized, few target molecules have been identified. Here, we used targeted DamID (TaDa) to identify Alk targets in embryos overexpressing Jeb versus embryos with abrogated Alk activity, revealing differentially expressed genes, including the Snail/Scratch family transcription factor Kahuli (Kah). We confirmed Kah mRNA and protein expression in the VM, and identified midgut constriction defects in Kah mutants similar to those of pointed (pnt). ChIP and RNA-Seq data analysis defined a Kah target-binding site similar to that of Snail, and identified a set of common target genes putatively regulated by Kah and Pnt during midgut constriction. Taken together, we report a rich dataset of Alk-responsive loci in the embryonic VM and functionally characterize the role of Kah in the regulation of embryonic midgut morphogenesis.

Funder

Cancerfonden

Barncancerfonden

Vetenskapsrådet

Stiftelsen för Strategisk Forskning

Göran Gustafssons Stiftelser

Åke Wiberg Stiftelser

Knut och Alice Wallenbergs Stiftelse

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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