title: Control of tissue growth by Yap relies on cell density and F-actin in zebrafish fin regeneration.
abstract: Caudal fin regeneration is characterized by a proliferation boost in the mesenchymal blastema that is controlled precisely in time and space. This allows a gradual and robust restoration of original fin size. However, how this is established and regulated is not well understood. Here, we report that Yap, the Hippo pathway effector, is a chief player in this process: functionally manipulating Yap during regeneration dramatically affects cell proliferation and expression of key signaling pathways, impacting regenerative growth. The intracellular location of Yap is tightly associated with different cell densities along the blastema proximal-distal axis, which correlate with alterations in cell morphology, cytoskeleton and cell-cell contacts in a gradient-like manner. Importantly, Yap inactivation occurs in high cell density areas, conditional to F-actin distribution and polymerization. We propose that Yap is essential for fin regeneration and that its function is dependent on mechanical tension, conferred by a balancing act of cell density and cytoskeleton activity.
authors.affiliation: CEDOC, NOVA Medical School, NOVA University of Lisbon, Campo Mártires da Pátria 130, Lisboa 1169-056, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Mateus
authors.affiliation: CEDOC, NOVA Medical School, NOVA University of Lisbon, Campo Mártires da Pátria 130, Lisboa 1169-056, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Lourenço
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC 27709, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal.
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Brito
authors.affiliation: CEDOC, NOVA Medical School, NOVA University of Lisbon, Campo Mártires da Pátria 130, Lisboa 1169-056, Portugal Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1649-028, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Farinho
authors.affiliation: CEDOC, NOVA Medical School, NOVA University of Lisbon, Campo Mártires da Pátria 130, Lisboa 1169-056, Portugal.
authors.forename: Fábio
authors.initials: F
authors.lastname: Valério
authors.affiliation: CEDOC, NOVA Medical School, NOVA University of Lisbon, Campo Mártires da Pátria 130, Lisboa 1169-056, Portugal Instituto Gulbenkian Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal antonio.jacinto@fcm.unl.pt.
authors.forename: Antonio
authors.initials: A
authors.lastname: Jacinto
mesh_terms: D000199:Actins / Q000378:metabolism*; D058500:Animal Fins / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D016376:Oligonucleotides, Antisense / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D000091102:YAP-Signaling Proteins; D015027:Zebrafish / Q000378:metabolism / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D016376:Oligonucleotides, Antisense; D015534:Trans-Activators; D000091102:YAP-Signaling Proteins; C583457:Yes-associated protein (yap), zebrafish; D029961:Zebrafish Proteins
keywords: Cell density; F-actin; Fin regeneration; Hippo/Yap; Zebrafish