Neurocentre Magendie

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15/02/2019 11h30
Isabelle Brunet, Collège de France - Molecular Control of Neuro-Vascular Development

Meeting room: CGFB Seminar room

Invitant : Mireille Montcouquiol (Neurocentre Magendie, Montcouquiol-Sans's lab)

Sympathetic arterial innervation and EphrinaA4/EPHA4 Signaling: Arteries under pressure?

Arteries receive a sympathetic innervation which is crucial to control their contraction level. Sympathetic nerves establish „“en passant““ synapses, called neurovascular junctions with arterial smooth muscle cells. Gene expres- sion comparison of non-innervated and innervated arteries revealed that the re- pulsive axon guidance molecule EphrinA4 is surprisingly expressed by arteries ar the onset of innervation (Postnatal day 2 P2). We here investigated the role of EphrinA4 signalization in the development and physiology of arterial innervation in mice. We showed that EphrinA4 is expressed by smooth muscle cells of resistance arteries and identified its receptor EphA4, expressed by sympathetic neurons. Binding and collapse experiments showed that EphrinA4 mediates the collapse of sympathetic growth cones in vitro via EphA4. EphrinA4 KO and EphA4 KO mice exhibited an increased arterial innervation at P2, consistent with a loss of repulsion. We then generated EphA4 flox-TH CRE mice who exhibited the same enhanced arterial innervation at P2 , which remained in adult mice. Increased arterial innervation in EPhA4 flox-TH CRE mice was correlated with a higher number of neurovascular junctions and a modifcation of their structure visible by eletronic microscopy. Measurement of cutaneous blood flow using laser doppler revealed an enhanced vasoconstriction in this mice. Resistivity and pulstility index of ca- rotids calculated from ultrasound views were increased, suggesting enhanced vascular resistivity. Thus EphrinA4 expressed by arterial smooth muscles cells induces collapse of sympathetic growth cones via the receptor EphA4 to refine sympathetic arterial innervation. Impairment of EphrinA4/EphA4 signaling leads to increased arterial innervation, vascular resistance and vasoconstriction. As systemic blood pressure depends on cardiac output but also vascular resistance, we are currently testing if those functional defects could lead to hypertension from sympathetic origin, or at least aggravate pre-existing hypertension.

Selected publications

– Minocha, S., Valloton, D., Brunet, I., Eichmann, A., Hornung, J.-P., Lebrand, C., (2015), NG2 glia are required for vessel network formation during embryonic development. Elife 4.

– Aspalter, I.M., Gordon, E., Dubrac, A., Ragab, A., Narloch, J., Vizán, P., Geudens, I., Collins, R.T., Franco, C.A., Abrahams, C.L., Thurston, G., Fruttiger, M., Rosewell, I., Eichmann, A., Gerhardt, H., (2015). Alk1 and Alk5 inhibition by Nrp1 controls vascular sprouting downstream of Notch. Nat Commun 6, 7264.

– Fortuna, V., Pardanaud, L., Brunet, I., Ola, R., Ristori, E., Santoro, M.M., Nicoli, S., and Eichmann, A. (2015). Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons. Cell Rep 11, 1786–1796.

– Rama N., Dubrac A., Mathivet T., Ní Chárthaigh R.-A., Genet G., Cristofaro B., Pibouin-Fragner L., Ma L., Eichmann A. & Chédotal A. (2015), Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization. Nat. Med. 21, 483–491.

28/11/2018 10h00
Mehdi BHOURI from Montcouquiol-Sans's lab will give a presentation entitled 'Role of the planar cell polarity protein Vangl2 in hippocampal circuits involved in memory.'

31/10/2018 10h00
Jerome EZAN from Montcouquiol-Sans's lab will give a presentation entitled 'Magendie Scientific life: why it is important to register to Hot-topics'

30/05/2018 10h30
Stephanie MAURIAC from Montcouquiol-Sans's lab will give a presentation entitled ' Identification of a common molecular basis leading to hearing deficit and corpus callosum agenesis in a rare disease'.

28/02/2018 10h00
Ana DORREGO-RIVAS from Montcouquiol-Sans's lab will give a presentation entitled "The Axonal Initial Segment (AIS): a hub for cell polarity ?"

PhD/HDR defense
04/12/2017 14h30
Benjamin Robert Benjamin Robert from the Montcouquiol-Sans' lab will defend his Ph.D. thesis entitled « Rôle de la signalisation de la polarité cellulaire planaire dans les processus mnésiques »

Benjamin Robert from the Montcouquiol-Sans' lab will defend his Ph.D. thesis entitled « Rôle de la signalisation de la polarité cellulaire planaire dans les processus mnésiques »
Date de la soutenance: 04/12/2017 - 14h30
Lieu: Neurocentre Magendie Seminar room

Pour plus de détails:

07/06/2017 12h00
Anne QUIEDEVILLE from Montcouquiol-Sans's lab will give a presentation entitled "Shank3 and autism spectrum disorders, focus on the hippocampus"

Notre publication parue en Avril 2017 dans Nature Communications porte sur un nouveau rôle de la
protéine Gpsm2 dans le contrôle de la dynamique du cytosquelette d’actine. Elle est relayée par le
Magazine Sciences et Santé de l'Inserm.

General informations
Workshop: How to get more out of your behavioral data – tips and tricks

Did you ever wish:
• To exchange with other behavioral scientists in an informal atmosphere?
• To learn more about the possibilities of EthoVision XT or other Noldus solutions?
• To see EthoVision XT in action in other research domains?
• To learn from other users, and see how they approach challenges like yours?
If the answer is yes, then we will be happy to meet you during the Noldus User Meeting at the Institut François Magendie,
on March 27th. This meeting will give you the possibility to meet other researchers, discuss your research projects, to get
practical information, and to learn how to exploit the full potential of Noldus solutions. Besides presentations, you will
have the possibility to get ‘hands-on’ experience with our systems during ‘ateliers’ (workshops) in small groups.

Diffusée par l'équipe Montcouquiol-Sans

Stéphanie Mauriac reçoit un prix "soutien étudiant" pour son travail sur le syndrome de Chudley-McCullough