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25
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Introduction
I’m interested in the molecular mechanisms that underlie proper brain wiring during development. Using mouse mutants, I currently investigate the role of certain genes in axon guidance, synaptic connectivity and, later on, in behavior as well as the potential involvement of these genes in neurodevelopmental disorders.
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Current institution
Publications
Publications (25)
Signal transduction downstream of axon guidance molecules is essential to steer developing axons. Second messengers including cAMP are key molecules shared by a multitude of signaling pathways and are required for a wide range of cellular processes including axon pathfinding. Yet, how these signaling molecules achieve specificity for each of their...
Signal transduction downstream of axon guidance molecules is essential to steer developing axons. Second messengers including cAMP are key molecules shared by a multitude of signaling pathways and are required for a wide range of cellular processes including axon pathfinding. Yet, how these signaling molecules achieve specificity for each of their...
Background
Heterozygous mutations or deletions of MEF2C cause a neurodevelopmental disorder termed MEF2C haploinsufficiency syndrome (MCHS), characterized by autism spectrum disorder and neurological symptoms. In mice, global Mef2c heterozygosity has produced multiple MCHS-like phenotypes. MEF2C is highly expressed in multiple cell types of the dev...
EphB1 is required for proper guidance of cortical axon projections during brain development, but how EphB1 regulates this process remains unclear. We show here that EphB1 conditional knockout (cKO) in GABAergic cells (Vgat-Cre), but not in cortical excitatory neurons (Emx1-Cre), reproduced the cortical axon guidance defects observed in global EphB1...
Chronic stress can produce reward system deficits (i.e., anhedonia) and other common symptoms associated with depressive disorders, as well as neural circuit hypofunction in the medial prefrontal cortex (mPFC). However, the molecular mechanisms by which chronic stress promotes depressive-like behavior and hypofrontality remain unclear. We show here...
Methamphetamine (METH) abuse is associated with the emergence of cognitive deficits and hypofrontality, a pathophysiological marker of many neuropsychiatric disorders that is produced by altered balance of local excitatory and inhibitory synaptic transmission. However, there is a dearth of information regarding the cellular and synaptic mechanisms...
BACKGROUND
Chronic methamphetamine (METH) abuse is associated with the emergence of cognitive deficits and hypofrontality, a pathophysiological marker of many neuropsychiatric disorders that is produced by altered balance of local excitatory and inhibitory synaptic transmission. However, there is a dearth of information regarding the cellular and s...
EphB1 is required for proper guidance of cortical long-range axon projections during brain development, but how EphB1 regulates this process remains unclear. To determine the relevant cell types in which EphB1 functions for proper cortical axon guidance, we generated a new floxed EphB1 mouse. We show here that EphB1 conditional knockout (cKO) in mo...
Techniques enabling DNA delivery into mouse retinal cells using in utero electroporation are available. However, these techniques target the central retina and do not enable the electroporation of the ventro-temporal retina where ipsilateral retinal ganglion cells are located. Here, we describe a protocol to specifically electroporate the ventro-te...
Autism spectrum disorder (ASD) is characterized by impairments in social communication and interaction and restricted, repetitive behaviors. It is frequently associated with comorbidities, such as attention-deficit hyperactivity disorder, altered sensory sensitivity, and intellectual disability. A de novo nonsense mutation in EPHB2 (Q857X) was disc...
Axonal arbors in many neuronal networks are exuberant early during development and become refined by activity-dependent competitive mechanisms. Theoretical work proposed non-competitive interactions between co-active axons to co-stabilize their connections, but the demonstration of such interactions is lacking. Here, we provide experimental evidenc...
Axonal arbors in many neuronal networks are exuberant early during development and become refined by activity-dependent competitive mechanisms. Theoretical work proposed non-competitive interactions between co-active axons to co-stabilize their connections, but the demonstration of such interactions is lacking. Here, we provide experimental evidenc...
Background
Microdeletions of the MEF2C gene are linked to a syndromic form of autism termed MEF2C Haploinsufficiency Syndrome (MCHS). MEF2C hypofunction in neurons is presumed to underlie most of the MCHS symptoms. However, it is unclear in which cell populations MEF2C functions to regulate neurotypical development.
Methods
Multiple biochemical, m...
Projections from the nucleus accumbens to the ventral pallidum (VP) regulate relapse in animal models of addiction. The VP contains GABAergic (VPGABA) and glutamatergic (VPGlu) neurons, and a subpopulation of GABAergic neurons co-express enkephalin (VPPenk). Rabies tracing reveals that VPGlu and VPPenk neurons receive preferential innervation from...
Microdeletions of the MEF2C gene are linked to a syndromic form of autism termed MEF2C haploinsufficiency syndrome (MCHS). Here, we show that MCHS-associated missense mutations cluster in the conserved DNA binding domain and disrupt MEF2C DNA binding. DNA binding-deficient global Mef2c heterozygous mice (Mef2c-Het) display numerous MCHS-like behavi...
The MEF2 family of transcription factors regulate large programs of gene expression important for the development and maintenance of many tissues, including the brain. MEF2 proteins are regulated by neuronal synaptic activity, and they recruit several epigenetic enzymes to influence chromatin structure and gene expression during development and thr...
Neural activity is crucial for the refinement of neuronal connections during development, but the contribution of synaptic release mechanisms is not known. In the mammalian retina, spontaneous neural activity controls the refinement of retinal projections to the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC) to form appro...
The development of neuronal circuits is controlled by guidance molecules that are hypothesized to interact with the cholesterol-enriched domains of the plasma membrane termed lipid rafts. Whether such domains enable local intracellular signalling at the submicrometre scale in developing neurons and are required for shaping the nervous system connec...
The release of lipid raft-targeted bPAC light activation is sufficient to induce axon retraction.
Reconstruction of individual retinal axon arbors in the Superior Colliculus.
Supplementary Figures 1-8
Axons of retinal ganglion cells retracted upon exposure to ephrin A5.
