Valérie Cadamuro - Academia.edu (original) (raw)

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Papers by Valérie Cadamuro

Research paper thumbnail of Non-autonomous role of Cdc42 in cell-cell communication during collective migration

Developmental biology, 2017

Collective cell migration is involved in numerous processes both physiological, such as embryonic... more Collective cell migration is involved in numerous processes both physiological, such as embryonic development, and pathological such as metastasis. Compared to single cell migration, collective motion requires cell behaviour coordination through an as-yet poorly understood but critical cell-cell communication mechanism. Using Drosophila border cell migration, we show here that the small Rho GTPase Cdc42 regulates cell-cell communication. Indeed, we demonstrate that Cdc42 controls protrusion formation in a cell non-autonomous manner. Moreover, we found that the endocytic small GTPase Rab11, controls Cdc42 localisation to the periphery of migrating border cell clusters. Accordingly, over-expression of Cdc42 in border cells rescues the loss of Rab11 function. In addition, we showed that Cdc42 acts upstream of Moesin, a cytoskeletal regulator known to function downstream of rab11. Thus, our study positions Cdc42 as a new key player in cell-cell communication, acting downstream of Rab11.

Research paper thumbnail of PKCθ-induced phosphorylations control the ability of Fra-1 to stimulate gene expression and cancer cell migration

Research paper thumbnail of Mechanical Feedback through E-Cadherin Promotes Direction Sensing during Collective Cell Migration

Cell, 2014

E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual... more E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual cells on matrix. However, its contribution to migration of cells through cell-rich tissues is less clear. We developed an in vivo sensor of mechanical tension across E-cadherin molecules, which we combined with cell-type-specific RNAi, photoactivatable Rac, and morphodynamic profiling, to interrogate how E-cadherin contributes to collective migration of cells between other cells. Using the Drosophila ovary as a model, we found that adhesion between border cells and their substrate, the nurse cells, functions in a positive feedback loop with Rac and actin assembly to stabilize forward-directed protrusion and directionally persistent movement. Adhesion between individual border cells communicates direction from the lead cell to the followers. Adhesion between motile cells and polar cells holds the cluster together and polarizes each individual cell. Thus, E-cadherin is an integral component of the guidance mechanisms that orchestrate collective chemotaxis in vivo.

Research paper thumbnail of Determined about sex: Sex-testing in 45 primate species using a 2Y/1X sex-typing assay

Forensic Science International: Genetics, 2015

Sex-testing using molecular genetic technique is routinely used in the fields of forensics, popul... more Sex-testing using molecular genetic technique is routinely used in the fields of forensics, population genetics and conservation biology. However, none of the assay used so far allows a non-ambiguous and successful sex determination for human and non-human primate species. The most widely used method, AMELY/X, and its alternatives suffer from a set of drawbacks in humans and can rarely be used in New World primate species. Here, we designed a new sex-typing assay using a multiplexed PCR amplification of UTX and UTY-homologous loci and combined male-specific SRY locus. This method was successfully tested on 1048 samples, including 82 non-human primates from 45 Anthropoidea and Lemuriformes species and 966 human samples from 24 populations (Africans, Europeans, and South Americans). This sex-typing method is applicable across all primate species tested from Hominoidea to Indriidae, and also on various populations with different background origins; it represents a robust and cheap sex-typing assay to be used both by the anthropologist and primatologist communities.

Research paper thumbnail of Tracing Arab-Islamic Inheritance in Madagascar: Study of the Y-chromosome and Mitochondrial DNA in the Antemoro

PLoS ONE, 2013

Madagascar is located at the crossroads of the Asian and African worlds and is therefore of parti... more Madagascar is located at the crossroads of the Asian and African worlds and is therefore of particular interest for studies on human population migration. Within the large human diversity of the Great Island, we focused our study on a particular ethnic group, the Antemoro. Their culture presents an important Arab-Islamic influence, but the question of an Arab biological inheritance remains unresolved. We analyzed paternal (n=129) and maternal (n=135) lineages of this ethnic group. Although the majority of Antemoro genetic ancestry comes from sub-Saharan African and Southeast Asian gene pools, we observed in their paternal lineages two specific haplogroups (J1 and T1) linked to Middle Eastern origins. This inheritance was restricted to some Antemoro subgroups. Statistical analyses tended to confirm significant Middle Eastern genetic contribution. This study gives a new perspective to the large human genetic diversity in Madagascar.

Research paper thumbnail of A biochemical network controlling basal myosin oscillation

Nature communications, Mar 23, 2018

The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontane... more The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontaneously in a wide variety of systems. Although much of the signal cascade regulating myosin activity has been characterized, the origin of such oscillatory behavior is still unclear. Here, we show that basal myosin II oscillation in Drosophila ovarian epithelium is not controlled by actomyosin cortical tension, but instead relies on a biochemical oscillator involving ROCK and myosin phosphatase. Key to this oscillation is a diffusive ROCK flow, linking junctional Rho1 to medial actomyosin cortex, and dynamically maintained by a self-activation loop reliant on ROCK kinase activity. In response to the resulting myosin II recruitment, myosin phosphatase is locally enriched and shuts off ROCK and myosin II signals. Coupling Drosophila genetics, live imaging, modeling, and optogenetics, we uncover an intrinsic biochemical oscillator at the core of myosin II regulatory network, shedding light on...

Research paper thumbnail of Myosin II governs collective cell migration behaviour downstream of guidance receptor signalling

Border cell migration during Drosophila oogenesis is a potent model to study collective cell migr... more Border cell migration during Drosophila oogenesis is a potent model to study collective cell migration, a process involved in development and metastasis. Border cell clusters adopt two main types of behaviour during migration: linear and rotational. However, the molecular mechanism controlling the switch from one to the other is unknown. Here, we demonstrate that non-muscle Myosin II (NMII, also known as Spaghetti squash) activity controls the linear-to-rotational switch. Furthermore, we show that the regulation of NMII takes place downstream of guidance receptor signalling and is critical to ensure efficient collective migration. This study thus provides new insight into the molecular mechanism coordinating the different cell behaviours in a migrating cluster. Summary: Non-muscle myosin II (NMII) is the key regulator for the control of border cell behaviours. Positively regulated by EGFR, NMII induces the switch of border cell movement from linear to rotational.

Research paper thumbnail of PKCθ-mediated serine/threonine phosphorylations of FAK govern adhesion and protrusion dynamics within the lamellipodia of migrating breast cancer cells

Research paper thumbnail of PKCtheta controls invasion of triple-negative breast cancer by direct phosphorylation of FAK

European Journal of Cancer

Research paper thumbnail of Abstract B59: Control of invasion by PKC theta in triple-negative breast cancer

Research paper thumbnail of Non-autonomous role of Cdc42 in cell-cell communication during collective migration

Developmental biology, 2017

Collective cell migration is involved in numerous processes both physiological, such as embryonic... more Collective cell migration is involved in numerous processes both physiological, such as embryonic development, and pathological such as metastasis. Compared to single cell migration, collective motion requires cell behaviour coordination through an as-yet poorly understood but critical cell-cell communication mechanism. Using Drosophila border cell migration, we show here that the small Rho GTPase Cdc42 regulates cell-cell communication. Indeed, we demonstrate that Cdc42 controls protrusion formation in a cell non-autonomous manner. Moreover, we found that the endocytic small GTPase Rab11, controls Cdc42 localisation to the periphery of migrating border cell clusters. Accordingly, over-expression of Cdc42 in border cells rescues the loss of Rab11 function. In addition, we showed that Cdc42 acts upstream of Moesin, a cytoskeletal regulator known to function downstream of rab11. Thus, our study positions Cdc42 as a new key player in cell-cell communication, acting downstream of Rab11.

Research paper thumbnail of PKCθ-induced phosphorylations control the ability of Fra-1 to stimulate gene expression and cancer cell migration

Research paper thumbnail of Mechanical Feedback through E-Cadherin Promotes Direction Sensing during Collective Cell Migration

Cell, 2014

E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual... more E-cadherin is a major homophilic cell-cell adhesion molecule that inhibits motility of individual cells on matrix. However, its contribution to migration of cells through cell-rich tissues is less clear. We developed an in vivo sensor of mechanical tension across E-cadherin molecules, which we combined with cell-type-specific RNAi, photoactivatable Rac, and morphodynamic profiling, to interrogate how E-cadherin contributes to collective migration of cells between other cells. Using the Drosophila ovary as a model, we found that adhesion between border cells and their substrate, the nurse cells, functions in a positive feedback loop with Rac and actin assembly to stabilize forward-directed protrusion and directionally persistent movement. Adhesion between individual border cells communicates direction from the lead cell to the followers. Adhesion between motile cells and polar cells holds the cluster together and polarizes each individual cell. Thus, E-cadherin is an integral component of the guidance mechanisms that orchestrate collective chemotaxis in vivo.

Research paper thumbnail of Determined about sex: Sex-testing in 45 primate species using a 2Y/1X sex-typing assay

Forensic Science International: Genetics, 2015

Sex-testing using molecular genetic technique is routinely used in the fields of forensics, popul... more Sex-testing using molecular genetic technique is routinely used in the fields of forensics, population genetics and conservation biology. However, none of the assay used so far allows a non-ambiguous and successful sex determination for human and non-human primate species. The most widely used method, AMELY/X, and its alternatives suffer from a set of drawbacks in humans and can rarely be used in New World primate species. Here, we designed a new sex-typing assay using a multiplexed PCR amplification of UTX and UTY-homologous loci and combined male-specific SRY locus. This method was successfully tested on 1048 samples, including 82 non-human primates from 45 Anthropoidea and Lemuriformes species and 966 human samples from 24 populations (Africans, Europeans, and South Americans). This sex-typing method is applicable across all primate species tested from Hominoidea to Indriidae, and also on various populations with different background origins; it represents a robust and cheap sex-typing assay to be used both by the anthropologist and primatologist communities.

Research paper thumbnail of Tracing Arab-Islamic Inheritance in Madagascar: Study of the Y-chromosome and Mitochondrial DNA in the Antemoro

PLoS ONE, 2013

Madagascar is located at the crossroads of the Asian and African worlds and is therefore of parti... more Madagascar is located at the crossroads of the Asian and African worlds and is therefore of particular interest for studies on human population migration. Within the large human diversity of the Great Island, we focused our study on a particular ethnic group, the Antemoro. Their culture presents an important Arab-Islamic influence, but the question of an Arab biological inheritance remains unresolved. We analyzed paternal (n=129) and maternal (n=135) lineages of this ethnic group. Although the majority of Antemoro genetic ancestry comes from sub-Saharan African and Southeast Asian gene pools, we observed in their paternal lineages two specific haplogroups (J1 and T1) linked to Middle Eastern origins. This inheritance was restricted to some Antemoro subgroups. Statistical analyses tended to confirm significant Middle Eastern genetic contribution. This study gives a new perspective to the large human genetic diversity in Madagascar.

Research paper thumbnail of A biochemical network controlling basal myosin oscillation

Nature communications, Mar 23, 2018

The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontane... more The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontaneously in a wide variety of systems. Although much of the signal cascade regulating myosin activity has been characterized, the origin of such oscillatory behavior is still unclear. Here, we show that basal myosin II oscillation in Drosophila ovarian epithelium is not controlled by actomyosin cortical tension, but instead relies on a biochemical oscillator involving ROCK and myosin phosphatase. Key to this oscillation is a diffusive ROCK flow, linking junctional Rho1 to medial actomyosin cortex, and dynamically maintained by a self-activation loop reliant on ROCK kinase activity. In response to the resulting myosin II recruitment, myosin phosphatase is locally enriched and shuts off ROCK and myosin II signals. Coupling Drosophila genetics, live imaging, modeling, and optogenetics, we uncover an intrinsic biochemical oscillator at the core of myosin II regulatory network, shedding light on...

Research paper thumbnail of Myosin II governs collective cell migration behaviour downstream of guidance receptor signalling

Border cell migration during Drosophila oogenesis is a potent model to study collective cell migr... more Border cell migration during Drosophila oogenesis is a potent model to study collective cell migration, a process involved in development and metastasis. Border cell clusters adopt two main types of behaviour during migration: linear and rotational. However, the molecular mechanism controlling the switch from one to the other is unknown. Here, we demonstrate that non-muscle Myosin II (NMII, also known as Spaghetti squash) activity controls the linear-to-rotational switch. Furthermore, we show that the regulation of NMII takes place downstream of guidance receptor signalling and is critical to ensure efficient collective migration. This study thus provides new insight into the molecular mechanism coordinating the different cell behaviours in a migrating cluster. Summary: Non-muscle myosin II (NMII) is the key regulator for the control of border cell behaviours. Positively regulated by EGFR, NMII induces the switch of border cell movement from linear to rotational.

Research paper thumbnail of PKCθ-mediated serine/threonine phosphorylations of FAK govern adhesion and protrusion dynamics within the lamellipodia of migrating breast cancer cells

Research paper thumbnail of PKCtheta controls invasion of triple-negative breast cancer by direct phosphorylation of FAK

European Journal of Cancer

Research paper thumbnail of Abstract B59: Control of invasion by PKC theta in triple-negative breast cancer