VEGFR2 (KDR/Flk1) Signaling Mediates Axon Growth in Response to Semaphorin 3E in the Developing Brain

Bellon, Anaïs; Luchino, Jonathan; Haigh, Katharina; Rougon, Geneviève; Haigh, Jody J.; Chauvet, Sophie; Mann, Fanny

doi:10.1016/j.neuron.2010.04.006

Cited by 119 publications

(143 citation statements)

References 42 publications

Supporting

Mentioning

138

Contrasting

Unclassified

Order By: Relevance

“…The SEMA3E gene encodes a secreted class 3 semaphorin that triggers repulsion of endothelial cells in specific vascular beds (9,10) and modulates axonal growth and synaptic connectivity for the correct wiring of the CNS (11)(12)(13). Unexpectedly, we found that the SEMA3E mutation, rather than affecting axon guidance in the GnRH neuron system, instead compromised survival signaling in GnRH neurons via PI3 kinase.…”

Section: Introductionmentioning

confidence: 62%

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome

Cariboni¹,

Andrè²,

Chauvet³

et al. 2015

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

International audienceIndividuals with an inherited deficiency in gonadotropin-releasing hormone (GnRH) have impaired sexual reproduction. Previous genetic linkage studies and sequencing of plausible gene candidates have identified mutations associated with inherited GnRH deficiency, but the small number of affected families and limited success in validating candidates have impeded genetic diagnoses for most patients. Using a combination of exome sequencing and computational modeling, we have identified a shared point mutation in semaphorin 3E (SEMA3E) in 2 brothers with Kallmann syndrome (KS), which causes inherited GnRH deficiency. Recombinant wild-type SEMA3E protected maturing GnRH neurons from cell death by triggering a plexin D1-dependent (PLXND1-dependent) activation of PI3K-mediated survival signaling. In contrast, recombinant SEMA3E carrying the KS-associated mutation did not protect GnRH neurons from death. In murine models, lack of either SEMA3E or PLXND1 increased apoptosis of GnRH neurons in the developing brain, reducing innervation of the adult median eminence by GnRH-positive neurites. GnRH neuron deficiency in male mice was accompanied by impaired testes growth, a characteristic feature of KS. Together, these results identify SEMA3E as an essential gene for GnRH neuron development, uncover a neurotrophic function for SEMA3E in the developing brain, and elucidate SEMA3E/PLXND1/PI3K signaling as a mechanism that prevents GnRH neuron deficiency

show abstract

Section: Introductionmentioning

confidence: 62%

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome

Cariboni¹,

Andrè²,

Chauvet³

et al. 2015

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In fact, current experiments of our laboratory are exploring this challenging hypothesis. In a broad sense, the effects of Sema3E/PlexinD1 on axon guidance can be categorized as inhibitory (present results, see also refs 30,53,55,61) or attractive 30,61 , depending on the presence of co-receptors Neuropilin 1 and VEGFR2, but more importantly on specific binding partners in the PlexinD1 cytoplasmic tail (see refs 28,36,62 for reviews). Neither Neuropilin 1 nor 2 is expressed by CR cells 63 ; this is restricted to the principal cortical neurons 64,65 .…”

Section: Discussionmentioning

confidence: 90%

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

et al. 2014

Self Cite

View full text Add to dashboard Cite

During the development of the cerebral cortex, Cajal-Retzius (CR) cells settle in the preplate and coordinate the precise growth of the neocortex. Indeed, CR cells migrate tangentially from specific proliferative regions of the telencephalon (for example, the cortical hem (CH)) to populate the entire cortical surface. This is a very finely tuned process regulated by an emerging number of factors that has been sequentially revealed in recent years. However, the putative participation of one of the major families of axon guidance molecules in this process, the Semaphorins, was not explored. Here we show that Semaphorin-3E (Sema3E) is a natural negative regulator of the migration of PlexinD1-positive CR cells originating in the CH. Our results also indicate that Sema3E/PlexinD1 signalling controls the motogenic potential of CR cells in vitro and in vivo. Indeed, absence of Sema3E/PlexinD1 signalling increased the migratory properties of CR cells. This modulation implies negative effects on CXCL12/CXCR4 signalling and increased ADF/Cofilin activity.

show abstract

“…Instead, VEGFR2 might convey VEGF-A signals in select subsets of neurons, for example to control axon pathfinding across the spinal cord midline (see below). Additionally, VEGFR2 can act in a complex with NRP1 and the semaphorin receptor plexin D1 to convey semaphorin signals in axon guidance (Bellon et al, 2010).…”

Section: Vegf-a Receptors In Neuronsmentioning

confidence: 99%

Diverse roles for VEGF-A in the nervous system

2012

View full text Add to dashboard Cite

Vascular endothelial growth factor A (VEGF-A) is best known for its essential roles in blood vessel growth. However, evidence has emerged that VEGF-A also promotes a wide range of neuronal functions, both in vitro and in vivo, including neurogenesis, neuronal migration, neuronal survival and axon guidance. Recent studies have employed mouse models to distinguish the direct effects of VEGF on neurons from its indirect, vessel-mediated effects. Ultimately, refining our knowledge of VEGF signalling pathways in neurons should help us to understand how the current use of therapeutics targeting the VEGF pathway in cancer and eye disease might be expanded to promote neuronal health and nerve repair.

show abstract

VEGFR2 (KDR/Flk1) Signaling Mediates Axon Growth in Response to Semaphorin 3E in the Developing Brain

Cited by 119 publications

References 42 publications

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome

Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome

Sema3E/PlexinD1 regulates the migration of hem-derived Cajal-Retzius cells in developing cerebral cortex

Diverse roles for VEGF-A in the nervous system

Contact Info

Product

Resources

About