Neurovascular Research Laboratory

Neurovascular Research Laboratory

Understanding development of the neuronal and vascular systems at the molecular level presents a major challenge to developmental biologists. Recent advances, including our own, conclusively show that similar molecules are recruited by both systems to coordinate development.

We are particularly interested in understanding the signalling pathway centred on VEGF and its Neuropilin receptors in neuronal development. Neural stem cells possess the exceptional ability to self-renew and differentiate into multiple cell types. During embryonic development, transient populations of neural stem cells give rise to the entire central and peripheral nervous systems.

We have recently identified essential roles of key signalling molecules in neuronal development and are now using genome-wide studies to characterise their functions in neuronal migration and differentiation.

Current research projects

  • Investigating the molecular control of neural crest stem cell (NCSC) development: To understand how Neuropilin (Nrp) receptors function in NCSC migration we are undertaking experiments to characterise the intracellular signalling pathways that control neuronal migration.
  • Identifying the embryonic origin of the childhood cancer Neuroblastoma: We have recently shown that the Nrp1 receptor is expressed in a subset of NCSCs that form neuroblastoma. This gives us the unique tools to dissect the aberrant genetic programs initiating tumour formation.
  • How does VEGF control development of the cardiac outflow tract? We have found that the Nrp1 receptor and its ligand VEGF are essential for NCSC development are and now addressing their role in cardiac development.
  • Investigating the role of 14-3-3ζ in schizophrenia: We have generated mice deficient in one of the 14-3-3 isoforms, 14-3-3ζ, and preliminary findings suggest these mice have behavioural issues akin to schizophrenia. We are now analysing the development of cerebral and hippocampal neurons in mouse models of 14-3-3 ζ.

Recent publications

1: Wiszniak S, Mackenzie FE, Anderson P, Kabbara S, Ruhrberg C, Schwarz Q. Neural crest cell-derived VEGF promotes embryonic jaw extension. Proc Natl Acad Sci U S A. 2015 Apr 28. pii: 201419368. [Epub ahead of print] PMID: 25922531.

2: Lumb R, Schwarz Q. Sympathoadrenal neural crest cells: the known, unknown and forgotten? Dev Growth Differ. 2015 Feb;57(2):146-57. PMID: 25581786.

3: Lumb R, Wiszniak S, Kabbara S, Scherer M, Harvey N, Schwarz Q. Neuropilins define distinct populations of neural crest cells. Neural Dev. 2014 Nov 3;9(1):24. PMID: 25363691.

4: Ramshaw H, Xu X, Jaehne EJ, McCarthy P, Greenberg Z, Saleh E, McClure B, Woodcock J, Kabbara S, Wiszniak S, Wang TY, Parish C, van den Buuse M, Baune BT, Lopez A, Schwarz Q. Locomotor hyperactivity in 14-3-3ζ KO mice is associated with dopamine transporter dysfunction. Transl Psychiatry. 2013 Dec 3;3:e327. PMID: 24301645.

5: Wiszniak S, Kabbara S, Lumb R, Scherer M, Secker G, Harvey N, Kumar S, Schwarz Q. The ubiquitin ligase Nedd4 regulates craniofacial development by promoting cranial neural crest cell survival and stem-cell like properties. Dev Biol. 2013 Nov 15;383(2):186-200. PMID: 24080509.

6: Wiszniak S, Lumb R, Kabbara S, Scherer M, Schwarz Q. Li-gazing at the crest: modulation of the neural crest by the ubiquitin pathway. Int J Biochem Cell Biol. 2013 Jun;45(6):1087-91. PMID: 23458963.

7: Maden CH, Gomes J, Schwarz Q, Davidson K, Tinker A, Ruhrberg C. NRP1 and NRP2 cooperate to regulate gangliogenesis, axon guidance and target innervation in the sympathetic nervous system. Dev Biol. 2012 Sep 15;369(2):277-85. PMID: 22790009.

8: Cheah PS, Ramshaw HS, Thomas PQ, Toyo-Oka K, Xu X, Martin S, Coyle P, Guthridge MA, Stomski F, van den Buuse M, Wynshaw-Boris A, Lopez AF, Schwarz QP. Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency. Mol Psychiatry. 2012 Apr;17(4):451-66. PMID: 22124272.

9: Fantin A, Schwarz Q, Davidson K, Normando EM, Denti L, Ruhrberg C. The cytoplasmic domain of neuropilin 1 is dispensable for angiogenesis, but promotes the spatial separation of retinal arteries and veins. Development. 2011 Oct;138(19):4185-91. PMID:21852397.

10: Cariboni A, Davidson K, Dozio E, Memi F, Schwarz Q, Stossi F, Parnavelas JG,  Ruhrberg C. VEGF signalling controls GnRH neuron survival via NRP1 independently of KDR and blood vessels. Development. 2011 Sep;138(17):3723-33. PMID: 21828096.

11: Erskine L, Reijntjes S, Pratt T, Denti L, Schwarz Q, Vieira JM, Alakakone B, Shewan D, Ruhrberg C. VEGF signaling through neuropilin 1 guides commissural axon crossing at the optic chiasm. Neuron. 2011 Jun 9;70(5):951-65. PMID: 21658587.