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Robo signalling controls pancreatic progenitor identity by regulating Tead transcription factors

Research output: Contribution to journalArticle

Sophie Escot, David Willnow, Heike Anita Naumann, Silvia DiFrancescantonio, Francesca Maria Spagnoli

Original languageEnglish
Article number5082
JournalNature Communications
Volume9
Early online date30 Nov 2018
DOIs
Accepted/In press5 Nov 2018
E-pub ahead of print30 Nov 2018
Published2018

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Abstract

A complex interplay of intrinsic factors and extrinsic signalling pathways controls both cell lineage commitment and maintenance of cell identity. Loss of defined cellular states is the cause of many different cancers, including pancreatic cancer. Recent findings suggest a clinical role for the conserved SLIT/ROBO signalling pathway in pancreatic cancer. However, whilst this pathway has been extensively studied in many processes, a role for Slit and Robo genes in pancreas cell identity and plasticity has not been established yet. Here, we identify Slit/Robo signalling as a key regulator of pancreatic progenitor identity. We find that Robo1 and Robo2 are required for preserving pancreatic cell identity shortly after fate induction and, subsequently, for expansion of the pancreatic progenitor pool in the mouse. Furthermore, we show that Robo receptors control the expression of Tead transcription factors as well as its downstream transcriptional activity. Our work identifies an interplay between Slit/Robo pathway and Tead intrinsic regulators, functioning as gatekeeper of pancreatic cell identity.

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