Growth across scales: Dynamic signaling impacts tissue size and shape

Organ and tissue growth result from an integration of biophysical communication across biological scales, both in time and space. In this review, we highlight new insight into the dynamic connections between control mechanisms operating at different length scales. First, we consider how the dynamics of chemical and electrical signaling in the shape of gradients or waves affect spatiotemporal signal interpretation. Then, we discuss the mechanics underlying dynamic cell behavior during oriented tissue growth, followed by the connections between signaling at the tissue and organismal levels.

Rita Mateus#, Jana Fuhrmann, Natalie Dye#: Growth across scales: Dynamic signaling impacts tissue size and shapeCurr Opin Cell Biol, 73 50-57 (2021)

This was a collaboration between the Mateus and Dye labs. More news about this work here

BMP Signaling Gradient Scaling in the Zebrafish Pectoral Fin

Secreted growth factors can act as morphogens that form spatial concentration gradients in developing organs, thereby controlling growth and patterning. For some morphogens, adaptation of the gradients to tissue size allows morphological patterns to remain proportioned as the organs grow. In the zebrafish pectoral fin, we found that BMP signaling forms a two-dimensional gradient. The length of the gradient scales with tissue length and its amplitude increases with fin size according to a power-law. Gradient scaling and amplitude power-laws are signatures of growth control by time derivatives of morphogenetic signaling: cell division correlates with the fold change over time of the cellular signaling levels. We show that Smoc1 regulates BMP gradient scaling and growth in the fin. Smoc1 scales the gradient by means of a feedback loop: Smoc1 is a BMP agonist and BMP signaling represses Smoc1 expression. Our work uncovers a layer of morphogen regulation during vertebrate appendage development.

Rita Mateus✳︎, Laurent Holtzer✳︎, Carole Seum, Zena Hadjivasiliou, Marine Dubois, Frank Jülicher, Marcos Gonzalez-Gaitan: BMP Signaling Gradient Scaling in the Zebrafish Pectoral FinCell Rep, 30(12) 4292-4302 (2020)

Control of tissue growth by Yap relies on cell density and F-actin in zebrafish fin regeneration

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.

Rita Mateus, Raquel Lourenço, Yi Fang, Goncalo Brito, Ana Farinho, Fábio Valério, Antonio Jacinto: Control of tissue growth by Yap relies on cell density and F-actin in zebrafish fin regenerationDevelopment, 142(16) 2752-2763 (2015)

Selected Publications

* joint first author # joint corresponding author

2021
Rita Mateus#, Jana Fuhrmann, Natalie Dye#
Growth across scales: Dynamic signaling impacts tissue size and shape.
Curr Opin Cell Biol, 73 50-57 (2021)
Open Access DOI
Organ and tissue growth result from an integration of biophysical communication across biological scales, both in time and space. In this review, we highlight new insight into the dynamic connections between control mechanisms operating at different length scales. First, we consider how the dynamics of chemical and electrical signaling in the shape of gradients or waves affect spatiotemporal signal interpretation. Then, we discuss the mechanics underlying dynamic cell behavior during oriented tissue growth, followed by the connections between signaling at the tissue and organismal levels.


2020
Rita Mateus✳︎, Laurent Holtzer✳︎, Carole Seum, Zena Hadjivasiliou, Marine Dubois, Frank Jülicher, Marcos Gonzalez-Gaitan
BMP Signaling Gradient Scaling in the Zebrafish Pectoral Fin.
Cell Rep, 30(12) 4292-4302 (2020)
Open Access DOI
Secreted growth factors can act as morphogens that form spatial concentration gradients in developing organs, thereby controlling growth and patterning. For some morphogens, adaptation of the gradients to tissue size allows morphological patterns to remain proportioned as the organs grow. In the zebrafish pectoral fin, we found that BMP signaling forms a two-dimensional gradient. The length of the gradient scales with tissue length and its amplitude increases with fin size according to a power-law. Gradient scaling and amplitude power-laws are signatures of growth control by time derivatives of morphogenetic signaling: cell division correlates with the fold change over time of the cellular signaling levels. We show that Smoc1 regulates BMP gradient scaling and growth in the fin. Smoc1 scales the gradient by means of a feedback loop: Smoc1 is a BMP agonist and BMP signaling represses Smoc1 expression. Our work uncovers a layer of morphogen regulation during vertebrate appendage development.


2019
Ana S Brandão, Anabela Bensimon-Brito#, Raquel Lourenço, Jorge Borbinha, Ana Rosa Soares, Rita Mateus, António Jacinto#
Yap induces osteoblast differentiation by modulating Bmp signalling during zebrafish caudal fin regeneration.
J Cell Sci, 132(22) Art. No. jcs231993 (2019)
DOI
Osteoblast differentiation is a key process for bone homeostasis and repair. Multiple signalling pathways have been associated with osteoblast differentiation, yet much remains unknown on how this process is regulated in vivo Previous studies have proposed that the Hippo pathway transcriptional co-activators YAP and TAZ (also known as YAP1 and WWTR1, respectively) maintain progenitor stemness and inhibit terminal differentiation of osteoblasts, whereas others suggest they potentiate osteoblast differentiation and bone formation. Here, we use zebrafish caudal fin regeneration as a model to clarify how the Hippo pathway regulates de novo bone formation and osteoblast differentiation. We demonstrate that Yap inhibition leads to accumulation of osteoprogenitors and prevents osteoblast differentiation in a cell non-autonomous manner. This effect correlates with a severe impairment of Bmp signalling in osteoblasts, likely by suppressing the expression of the ligand bmp2a in the surrounding mesenchymal cells. Overall, our findings provide a new mechanism of bone formation through the Hippo-Yap pathway, integrating Yap in the signalling cascade that governs osteoprogenitor maintenance and subsequent differentiation during zebrafish caudal fin regeneration.


2015
Rita Mateus, Raquel Lourenço, Yi Fang, Goncalo Brito, Ana Farinho, Fábio Valério, Antonio Jacinto
Control of tissue growth by Yap relies on cell density and F-actin in zebrafish fin regeneration.
Development, 142(16) 2752-2763 (2015)
DOI
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.


2012
Rita Mateus, Telmo Pereira, Sara Sousa, Joana Esteves de Lima, Susana Pascoal, Leonor Saúde, Antonio Jacinto
In vivo cell and tissue dynamics underlying zebrafish fin fold regeneration.
PLoS ONE, 7(12) Art. No. e51766 (2012)
Open Access DOI
Zebrafish (Danio rerio) has a remarkable capacity to regenerate many organs and tissues. During larval stages the fin fold allows the possibility of performing long time-lapse imaging making this system very appealing to study the relationships between tissue movements, cell migration and proliferation necessary for the regeneration process.