Neural migration

About

Current research in the Cooper laboratory explores the fundamental cellular and molecular mechanisms governing the development of the neocortex. The group has identified unexpected, novel roles for the axon guidance receptors Neogenin (a netrin receptor) and Ryk (a Wnt receptor) in neural stem cell biology, neurogenesis, dendrite outgrowth and synaptogenesis. The Cooper group has shown that loss of these receptors in the mouse leads to cortical malformations which are equivalent to those seen in humans.

The group’s latest studies are providing a mechanistic understanding of how these signalling pathways ensure the fidelity of cortical development. The laboratory has also uncovered intriguing links between these receptors and genes associated with schizophrenia and autism. The Cooper laboratory believes that these studies will produce fundamental insights into the pathophysiology of cortical malformations and perhaps provide some clues to the molecular basis of neuropsychiatric disorders. 

Importantly, to ensure that discoveries are relevant to the human brain, the group has also initiated a collaboration with Professor Ernst Wolvetang (AIBN, UQ) to investigate these signalling pathways in human induced pluripotent stem cells, which can generate embryonic neural stem cells and many neuronal subtypes found in the neocortex. In the coming years the laboratory hopes to identify new modulators of neurogenesis and neuronal connectivity. The Cooper group will also explore the functions of genes known to carry mutations that contribute to cortical malformations and neuropsychiatric disorders.

Contact

  +61 7 334 66354

  h.cooper@uq.edu.au


Group Publications

Research Areas

  • Neocortex development
  • Axon guidance receptors
  • Scizophrenia & autism
  • Pluripotent stem cells


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Group Leader

 


Research Members


Students


DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218

Torres-Berrío, Angélica, Lopez, Juan Pablo, Bagot, Rosemary C., Nouel, Dominique, Dal Bo, Gregory, Cuesta, Santiago, Zhu, Lei, Manitt, Colleen, Eng, Conrad, Cooper, Helen M., Storch, Kai-Florian, Turecki, Gustavo, Nestler, Eric J. and Flores, Cecilia (2017) DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218. Biological Psychiatry81 4: 306-315. doi:10.1016/j.biopsych.2016.08.017

Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension

Lee, Natalie K., Fok, Ka Wai, White, Amanda, Wilson, Nicole H., O’Leary, Conor J., Cox, Hayley L., Michael, Magdalene, Yap, Alpha S. and Cooper, Helen M. (2016) Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension. Nature Communications7 11082: . doi:10.1038/ncomms11082

Validating Eaton's hypothesis: cubane as a benzene bioisostere

Chalmers, Benjamin A., Xing, Hui, Houston, Sevan, Clark, Charlotte, Ghassabian, Sussan, Kuo, Andy, Cao, Benjamin, Reitsma, Andrea, Murray, Cody-Ellen P., Stok, Jeanette E., Boyle, Glen M., Pierce, Carly J., Littler, Stuart W., Winkler, David A., Bernhardt, Paul V., Pasay, Cielo, De Voss, James J., McCarthy, James, Parsons, Peter G., Walter, Gimme H., Smith, Maree T., Cooper, Helen M., Nilsson, Susan K., Tsanaktsidis, John, Savage, G. Paul and Williams, Craig M. (2016) Validating Eaton's hypothesis: cubane as a benzene bioisostere. Angewandte Chemie (International Edition)55 11: 3580-3585. doi:10.1002/anie.201510675

Crosslinking to enhance colloidal stability and redispersity of layered double hydroxide nanoparticles

Zuo, Huali, Gu, Zi, Cooper, Helen and Xu, Zhi Ping (2015) Crosslinking to enhance colloidal stability and redispersity of layered double hydroxide nanoparticles. Journal of Colloid and Interface Science459 10-16. doi:10.1016/j.jcis.2015.07.063

The Netrin/RGM receptor, neogenin, controls adult neurogenesis by promoting neuroblast migration and cell cycle exit

O'Leary, Conor J., Bradford, DanaKai, Chen, Min, White, Amanda, Blackmore, Daniel G. and Cooper, Helen M. (2014) The Netrin/RGM receptor, neogenin, controls adult neurogenesis by promoting neuroblast migration and cell cycle exit. Stem Cells33 2: 503-514. doi:10.1002/stem.1861

Engineering small MgAl-layered double hydroxide nanoparticles for enhanced gene delivery

Dong, Haiyan, Chen, Min, Rahman, Shafiur, Parekh, Harendra S., Cooper, Helen M. and Xu, Zhi Ping (2014) Engineering small MgAl-layered double hydroxide nanoparticles for enhanced gene delivery. Applied Clay Science,100 C: 66-75. doi:10.1016/j.clay.2014.04.028

Cytoplasmic dynein: a key player in neurodegenerative and neurodevelopmental diseases

Chen, Xiang-Jun, Xu, Huan, Cooper, Helen M. and Liu, Yaobo (2014) Cytoplasmic dynein: a key player in neurodegenerative and neurodevelopmental diseases. Science China Life Sciences57 4: 372-377. doi:10.1007/s11427-014-4639-9

The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration

Clark, Charlotte E. J., Liu, Yaobo and Cooper, Helen M. (2014) The Yin and Yang of Wnt/Ryk axon guidance in development and regeneration. Science China Life Sciences57 4: 366-371. doi:10.1007/s11427-014-4640-3

Wnt5a induces Ryk-dependent and -independent effects on callosal axon and dendrite growth

Clark, Charlotte E. J., Richards, , Linda J., Stacker, Steven A. and Cooper, Helen M. (2014) Wnt5a induces Ryk-dependent and -independent effects on callosal axon and dendrite growth. Growth Factors32 1: 11-17. doi:10.3109/08977194.2013.875544

Dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients

Manitt C., Eng C., Pokinko M., Ryan R.T., Torres-Berrio A., Lopez J.P., Yogendran S.V., Daubaras M.J.J., Grant A., Schmidt E.R.E., Tronche F., Krimpenfort P., Cooper H.M., Pasterkamp R.J., Kolb B., Turecki G., Wong T.P., Nestler E.J., Giros B. and Flores C. (2013) Dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients. Translational Psychiatry3 . doi:10.1038/tp.2013.105

Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine

Kim, Jee Hyun, Lavan, Doron, Chen, Nicola, Flores, Cecilia, Cooper, Helen and Lawrence, Andrew J. (2013) Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine. Psychopharmacology230 4: 607-616. doi:10.1007/s00213-013-3187-5

RGMa regulates cortical interneuron migration and differentiation

O'Leary, Conor, Cole, Stacey J., Langford, Michael, Hewage, Jayani, White, Amanda and Cooper, Helen M. (2013) RGMa regulates cortical interneuron migration and differentiation. PLoS One8 11: e81711.1-e81711.12. doi:10.1371/journal.pone.0081711

Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease

Reyes, Stefanie, Fu, Yuhong, Double, Kay L., Cottam, Veronica, Thompson, Lachlan H., Kirik, Deniz, Paxinos, George, Watson, Charles, Cooper, Helen M. and Halliday, Glenda M. (2013) Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease. Neurobiology of Aging34 3: 873-886. doi:10.1016/j.neurobiolaging.2012.07.019

Netrin-1 is required for efficient neural tube closure

Kee, Nigel, Wilson, Nicole, Key, Brian and Cooper, Helen (2013) Netrin-1 is required for efficient neural tube closure.Developmental Neurobiology73 2: 176-187. doi:10.1002/dneu.22051

One-pot preparation of highly fluorescent cadmium telluride/cadmium sulfide quantum dots under neutral-pH condition for biological applications

Zhu, Yian, Li, Zhen, Chen, Min, Cooper, Helen, Lu, Gao Qing (Max) and Xu, Zhi Ping (2013) One-pot preparation of highly fluorescent cadmium telluride/cadmium sulfide quantum dots under neutral-pH condition for biological applications. Journal of Colloid and Interface Science390 1: 3-10. doi:10.1016/j.jcis.2012.08.003

Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of siRNA delivery

Chen, Min, Helen Cooper, Zhou, Ji Zhi, Bartlett, Perry F. and Xu, Zhi Ping (2013) Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of siRNA delivery. Journal of Colloid and Interface Science,390 1: 275-281. doi:10.1016/j.jcis.2012.09.033

Tuning core-shell SiO2@CdTe@SiO2 fluorescent nanoparticles for cell labeling

Zhu, Yian, Li, Zhen, Chen, Min, Cooper, Helen M. and Xu, Zhi Ping (2013) Tuning core-shell SiO2@CdTe@SiO2 fluorescent nanoparticles for cell labeling. Journal of Materials Chemistry B1 17: 2315-2323. doi:10.1039/c3tb20202j

Multiple Slits regulate the development of midline glial populations and the corpus callosum

Unni, Divya K., Piper, Michael, Moldrich, Randal X., Gobius, Ilan, Liu, Sha, Fothergill, Thomas, Donahoo, Amber-Lee S., Baisden, John M., Cooper, Helen M. and Richards, Linda J. (2012) Multiple Slits regulate the development of midline glial populations and the corpus callosum. Developmental Biology365 1: 36-49. doi:10.1016/j.ydbio.2012.02.004

The tangled web of non-canonical Wnt signalling in neural migration

Clark, Charlotte E.J., Nourse, C. Cathrin and Cooper, Helen M. (2012) The tangled web of non-canonical Wnt signalling in neural migration. Neurosignals20 3: 202-220. doi:10.1159/000332153

Altered development of Xenopus embryos in a hypogeomagnetic field

Mo, Wei-chuan, Liu, Ying, Cooper, Helen M. and He, Rong-qiao (2012) Altered development of Xenopus embryos in a hypogeomagnetic field. Bioelectromagnetics33 3: 238-246. doi:10.1002/bem.20699

Efficiency of layered double hydroxide nanoparticle-mediated delivery of siRNA is determined by nucleotide sequence

Wong, Yunyi, Cooper, Helen M., Zhang, Kai, Chen, Min, Bartlett, Perry and Xu, Zhi Ping (2012) Efficiency of layered double hydroxide nanoparticle-mediated delivery of siRNA is determined by nucleotide sequence. Journal of Colloid and Interface Science369 1: 453-459. doi:10.1016/j.jcis.2011.12.046

Synthesis of robust sandwich-like SiO2@CdTe@SiO2 fluorescent nanoparticles for cellular imaging

Zhu, Yian, Li, Zhen, Chen, Min, Cooper, Helen M., Lu, Gao Qing (Max) and Xu, Zhi Ping (2012) Synthesis of robust sandwich-like SiO2@CdTe@SiO2 fluorescent nanoparticles for cellular imaging. Chemistry of Materials24 3: 421-423. doi:10.1021/cm2033417

Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice

Chawengsaksophak, Kallayanee, Svingen, Terje, Ng, Ee Ting, Epp, Trevor, Spiller, Cassy M., Clark, Charlotte, Cooper, Helen and Koopman, Peter (2012) Loss of Wnt5a disrupts primordial germ cell migration and male sexual development in mice. Biology of Reproduction86 1: 1-12. doi:10.1095/biolreprod.111.095232

Oncostatin M regulates neural precursor activity in the adult brain

Beatus, Paul, Jhaveri, Dhanisha J., Walker, Tara L., Lucas, Peter G., Rietze, Rodney L., Cooper, Helen M., Morikawa, Yoshihiro and Bartlett, Perry F. (2011) Oncostatin M regulates neural precursor activity in the adult brain.Developmental Neurobiology71 7: 619-633. doi:10.1002/dneu.20871

The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry

Manitt, Colleen, Mimee, Andrea, Eng, Conrad, Pokinko, Matthew, Stroh, Thomas, Cooper, Helen M., Kolb, Bryan and Flores, Cecilia (2011) The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry. The Journal of Neuroscience31 23: 8381-8394. doi:10.1523/JNEUROSCI.0606-11.2011

Sonic hedgehog and notch signaling can cooperate to regulate neurogenic divisions of neocortical progenitors

Dave, Richa K., Ellis, Tammy, Toumpas, Melissa C., Robson, Jonathan P., Julian, Elaine, Adolphe, Christelle, Bartlett, Perry F., Cooper, Helen M., Reynolds, Brent A. and Wainwright, Brandon J. (2011) Sonic hedgehog and notch signaling can cooperate to regulate neurogenic divisions of neocortical progenitors. PLoS One6 2: e14680-1-e14680-13. doi:10.1371/journal.pone.0014680

Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles

Wong, Yunyi, Markham, Kathryn, Xu, Zhi Ping, Chen, Min, Liu, Gao Qing (Max), Bartlett, Perry F. and Cooper, Helen M. (2010) Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles. Biomaterials,31 33: 8770-8779. doi:10.1016/j.biomaterials.2010.07.077

Characterization of the netrin/RGMa receptor neogenin in neurogenic regions of the mouse and human adult forebrain

Bradford, D., Faull, R. L. M., Curtis, M. A. and Cooper, H. M. (2010) Characterization of the netrin/RGMa receptor neogenin in neurogenic regions of the mouse and human adult forebrain. Journal of Comparative Neurology518 16: 3237-3253. doi:10.1002/cne.22397

Synthetic neovibsanes and their ability to induce neuronal differentiation in PC12 cells

Chen, Apj, Muller, CC, Cooper, HM and Williams, CM (2010) Synthetic neovibsanes and their ability to induce neuronal differentiation in PC12 cells. Tetrahedron66 34: 6842-6850. doi:10.1016/j.tet.2010.06.056

Total synthesis of (+/-)-4,5-Bis-epi-neovibsanin A and B: A neurite outgrowth comparison study

Chen, Annette P. -J., Müller, C. Catharina, Cooper, Helen M. and Williams, Craig M. (2009) Total synthesis of (+/-)-4,5-Bis-epi-neovibsanin A and B: A neurite outgrowth comparison study. Organic Letters11 16: 3758-3761. doi:10.1021/ol901406j

Netrin-1: Diversity in development

Bradford, Dana, Cole, Stacey and Cooper, Helen M. (2009) Netrin-1: Diversity in development. International Journal of Biochemistry & Cell Biology41 3: 487-493. doi:10.1016/j.biocel.2008.03.014

Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity

Kee, Nigel, Wilson, Nicole, De Vries, Melissa, Bradford, DanaKai, Key, Brian and Cooper, Helen M. (2008) Neogenin and RGMa control neural tube closure and neuroepithelial morphology by regulating cell polarity. The Journal of Neuroscience28 48: 12643-12653. doi:10.1523/JNEUROSCI.4265-08.2008

Subcellular compartment targeting of layered double hydroxide nanoparticles

Xu, Zhi Ping, Niebert, Marcus, Porazik, Katharina, Walker, Tara L., Cooper, Helen M., Middelberg, Anton P.J., Gray, Peter P., Bartlett, Perry F. and Lu, Gao Qing (Max) (2008) Subcellular compartment targeting of layered double hydroxide nanoparticles. Journal of Controlled Release130 1: 86-94. doi:10.1016/j.jconrel.2008.05.021

Emerging roles for neogenin and its ligands in CNS development

de Vries, Melissa and Cooper, Helen M. (2008) Emerging roles for neogenin and its ligands in CNS development.Journal Of Neurochemistry106 4: 1483-1492. doi:10.1111/j.1471-4159.2008.05485.x

Neogenin is expressed on neurogenic and gliogenic progenitors in the embryonic and adult central nervous system

Fitzgerald, D. P., Bradford, D. and Cooper, H. M. (2007) Neogenin is expressed on neurogenic and gliogenic progenitors in the embryonic and adult central nervous system. Gene Expression Patterns7 7: 784-792. doi:10.1016/j.modgep.2007.05.004

Layered double hydroxide nanoparticles as cellular delivery vectors of supercoiled plasmid DNA

Xu, Zhi Ping, Walker, Tara L., Liu, Kerh-lin, Cooper, Helen M., Lu, G. Q. Max and Bartlett, Perry F. (2007) Layered double hydroxide nanoparticles as cellular delivery vectors of supercoiled plasmid DNA. International Journal of Nanomedicine2 2: 163-174. doi:10.2147/IJN.S

Neogenin: A multi-functional receptor regulating diverse developmental processes

Cole, S. J., Bradford, D. and Cooper, H. M. (2007) Neogenin: A multi-functional receptor regulating diverse developmental processes. The International Journal of Biochemistry & Cell Biology39 9: 1569-1575. doi:10.1016/j.biocel.2006.11.009

Characterization of neogenin-expressing neural progenitor populations and migrating neuroblasts in the embryonic mouse forebrain

Fitzgerald, D. P., Cole, S. J., Hammond, A., Seaman, C. and Cooper, H. M. (2006) Characterization of neogenin-expressing neural progenitor populations and migrating neuroblasts in the embryonic mouse forebrain. Neuroscience,142 3: 703-716. doi:10.1016/j.neuroscience.2006.06.041

Localization of neogenin protein during morphogenesis in the mouse embryo

Fitzgerald, D. P., Seaman, C. and Cooper, H. M. (2006) Localization of neogenin protein during morphogenesis in the mouse embryo. Developmental Dynamics235 6: 1720-1725. doi:10.1002/dvdy.20744

Ryk: A novel Wnt receptor regulating axon pathfinding

Keeble, T. R. and Cooper, H. M. (2006) Ryk: A novel Wnt receptor regulating axon pathfinding. International Journal of Biochemistry & Cell Biology38 12: 2011-2017. doi:10.1016/j.biocel.2006.07.005

Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination

Emery, B., Cate, H. S., Marriottt, M., Merson, T., Binder, M. D., Snell, C., Soo, P. Y., Murray, S., Croker, B., Zhang, J. G., Alexander, W. S., Cooper, H., Butzkueven, H. and Kilpatrick, T. J. (2006) Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination. Proceedings of The National Academy of Sciences of The United States of America103 20: 7859-7864. doi:10.1073/pnas.0602574103

The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum

Keeble, T. R., Halford, M., Seaman, C., Kee, N., Macheda, M., Andersen, R. B., Stacker, S. A. and Cooper, H. M. (2006) The Wnt receptor Ryk is required for Wnt5a-mediated axon guidance on the contralateral side of the corpus callosum. Journal of Neuroscience26 21: 5840-5848. doi:10.1523/JNEUROSCI.1175-06.2006

Localization of immunoreactivity for deleted in colorectal cancer (DCC), the receptor for the guidance factor netrin-1, in ventral tier dopamine projection pathways in adult rodents

Osborne, P. B., Halliday, G. M., Cooper, H. M. and Keast, J. R. (2005) Localization of immunoreactivity for deleted in colorectal cancer (DCC), the receptor for the guidance factor netrin-1, in ventral tier dopamine projection pathways in adult rodents. Neuroscience131 3: 671-681. doi:10.1016/j.neuroscience.2004.11.043

The Netrin receptor Neogenin is required for neural tube formation and somitogenesis in zebrafish

Mawdsley, David J., Cooper, Helen M., Hogan, Benjamin M., Cody, Stephen H., Lieschke, Graham J. and Heath, Joan K. (2004) The Netrin receptor Neogenin is required for neural tube formation and somitogenesis in zebrafish.Developmental Biology269 1: 302-315. doi:10.1016/j.ydbio.2004.02.001

Schwann cell apoptosis in the postnatal axotomized sciatic nerve is mediated via NGF through the low-affinity neurotrophin receptor

Petratos, S., Butzkueven, H., Shipham, K., Cooper, H., Bucci, T., Reid, K., Lopes, E., Emery, B., Cheema, S. S. and Kilpatrick, T. J. (2003) Schwann cell apoptosis in the postnatal axotomized sciatic nerve is mediated via NGF through the low-affinity neurotrophin receptor. Journal of Neuropathology And Experimental Neurology62 4: 398-411.

Axon guidance receptors direct growth cone pathfinding: rivalry at the leading edge

Cooper, H. M. (2002) Axon guidance receptors direct growth cone pathfinding: rivalry at the leading edge.International Journal of Developmental Biology46 4: 621-631.

Localization of the netrin guidance receptor, DCC, in the developing peripheral and enteric nervous systems

Seaman, Clare, Anderson, Richard, Emery, Ben and Cooper, Helen M. (2001) Localization of the netrin guidance receptor, DCC, in the developing peripheral and enteric nervous systems. Mechanisms of Development103 1-2: 173-175. doi:10.1016/S0925-4773(01)00350-1

Netrin-3 protein is localized to the axons of motor, sensory, and sympathetic neurons

Seaman, Clare and Cooper, Helen M. (2001) Netrin-3 protein is localized to the axons of motor, sensory, and sympathetic neurons. Mechanisms of Development101 1-2: 245-248. doi:10.1016/S0925-4773(00)00563-3

A zebrafish homologue of deleted in colorectal cancer (zdcc) is expressed in the first neuronal clusters of the developing brain

Hjorth, J. T., Gad, J., Cooper, H. and Key, B. (2001) A zebrafish homologue of deleted in colorectal cancer (zdcc) is expressed in the first neuronal clusters of the developing brain. Mechanisms of Development109 1: 105-109. doi:10.1016/S0925-4773(01)00513-5

DCC plays a role in navigation of forebrain axons across the ventral midbrain commissure in embryonic Xenopus

Anderson, R. B., Cooper, H. M., Jackson, S. C., Seaman, C. and Key, B. (2000) DCC plays a role in navigation of forebrain axons across the ventral midbrain commissure in embryonic Xenopus. Developmental Biology217 2: 244-253. doi:10.1006/dbio.1999.9549


Understanding the role of autism genes in cortical development

Cortical malformations arising from abnormal neuronal positioning in the neocortex (neuronal heterotopias) are causative for intellectual disability and intractable childhood epilepsies.  Intriguingly, similar disruptions to the architecture of the neocortex are also observed in autistic children. Mutations in genes that regulate neural stem cell activity and neuronal migration have been implicated in both inherited cortical malformations and autism. This predicts that there is a common molecular mechanism contributing to both neuronal heterotopias and autism spectrum disorders. Our goal is to identify the pivotal molecular pathways that maintain neural stem cell function and neuronal migration in the developing brain and to uncover how mutations in genes implicated in autism impact cortical development.

We have identified the stem cell receptor, Neogenin, as an important regulator of neural stem cell activity and the migration of newborn neurons. We have shown that Neogenin controls the activity of genes known to be prominent risk factors for autism, intellectual disability and schizophrenia. Using mutant mouse and human induced pluripotent stem cell models, we are now exploring the role of this signaling pathway in the development of the neocortex. We are also investigating how mutations in these genes lead to the emergence of autism-like behaviors in our mouse models.

Understanding the molecular mechanisms responsible for hydrocephalus

Project 1
Foetal hydrocephalus is a prevalent neurodevelopmental condition (1 in 3000 births) associated with severe intellectual impairment and motor dysfunction. Ependymal cells (ECs) form a multi-ciliated epithelium at the ventricular surface and the inability to form a cohesive ependymal epithelium has emerged as a major cause of hydrocephalus. ECs are produced from a subpopulation of neural stem cells within the embryonic brain. The failure of these stem cells to produce mature ECs leads to hydrocephalus. Despite the fundamental importance of the stem cell to EC transition, our understanding of the molecular mechanisms governing this process is very limited.

Mutations in Neogenin lead to severe hydrocephalus in mice due to a failure in the production and maturation of ECs. Therefore the Neogenin signaling pathway is critical for the transition from stem cell to mature EC. The aim of our current research is to understand how silencing this pathway contributes to hydrocephalus and to provide proof-of-principle that enhancing Neogenin activity can prevent hydrocephalus.

Project 2 
The choroid plexus is the predominant supplier of cerebral spinal fluid, and abnormal choroid plexus function leads to excessive cerebral spinal fluid production and hydrocephalus. Therefore its importance in maintaining normal brain function is paramount. In this project we investigate the role of the Wnt signaling pathway in choroid plexus formation using loss-of-function and mutagenesis approaches in the developing mouse.

Understanding the molecular processes building complex neural circuits

The contribution of a given neuron to the information flow within the neural circuitry of the brain is governed by the unique three-dimensional architecture of the dendritic tree and the ability to form functional synapses. Abnormal dendritic growth and synapse formation lead to diminished synaptic connectivity and impaired cognitive function associated with neurodevelopmental conditions, including autism and schizophrenia, as well as neurodegenerative disorders such as Alzheimer’s disease. In this project we investigate the role of the Wnt and Neogenin signaling pathways in sculpting dendritic structure and the establishment of synaptic structures. 


Project 1: Does Neogenin and its ligands, netrin and RGMa, control neural stem cell function in induced pluripotent stem cells and the developing mouse cortex?

Project 2: Identifying the molecular mechanism through which Neogenin controls the actin cytoskeleton in migrating neurons and axons.

Project 3: Understanding the role of autism genes in cortical development

Project 4: Identifying signaling pathways contributing to ependymal cell differentiation and hydrocephalus.

Project 5: Investigating signaling pathways that control the actin cytoskeleton in mammalian dendrite morphogenesis and synaptogenesis.

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