Details

Autor(en) / Beteiligte

• Ragni, Chiara V.
• Diguet, Nicolas
• Le Garrec, Jean-François
• Novotova, Marta
• Resende, Tatiana P.
• Pop, Sorin
• Charon, Nicolas
• Guillemot, Laurent
• Kitasato, Lisa
• Badouel, Caroline
• Dufour, Alexandre
• Olivo-Marin, Jean-Christophe
• Trouvé, Alain
• McNeill, Helen
• Meilhac, Sigolène M

Titel

Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth

Ist Teil von

• Nature communications, 2017-02, Vol.8 (1), p.14582-14582, Article 14582

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway. Fat4 is not required for the canonical activation of Hippo kinases but it sequesters a partner of Yap1, Amotl1, out of the nucleus. The nuclear translocation of Amotl1 is accompanied by Yap1 to promote cardiomyocyte proliferation. We, therefore, identify Amotl1, which is not present in flies, as a mammalian intermediate for non-canonical Hippo signalling, downstream of Fat4. This work uncovers a mechanism for the restriction of heart growth at birth, a process which impedes the regenerative potential of the mammalian heart. Growth of the mammalian heart is controlled by Hippo signalling but how this is regulated is unclear. Here, the authors show that Fat4 (an atypical cadherin) acts upstream of Hippo signalling and Fat4 mutant mice have thicker myocardium, which is mediated by the scaffold Amot1 and transcription factor Yap1.