Brain development and disorders lab
Key breakthroughs & discoveries
In this same area, the laboratory was awarded a National Institutes of Health grant with Professor Elliott Sherr (University of California, San Francisco) and Professor Bill Dobyns (Seattle University, Washington) who are internationally leading paediatric neurologists and geneticists, and a National Health and Medical Research Council grant with Professor Sherr and QBI researcher Associate Professor Tom Burne. These grants will specifically identify genes that cause human developmental brain disorders, and investigate their function.
Over the past 23 years, my work has uncovered three fundamental principles in brain wiring (see Paul et al., 2007 and Edwards et al., 2014 for seminal reviews): 1) callosal axons interact with glia in a critically dependent manner (Shu and Richards, 2001; Shu et al., 2003a; Gobius et al., 2016), 2) callosal axons express intrinsic guidance receptors (Shu et al., 2003b, Marsh et al., 2017), and 3) balanced interhemispheric neuronal activity is required for callosal targeting (Suárez et al., 2014). These discoveries have established the major fundamental mechanisms required for formation of the corpus callosum and form the rationale for my election to two learned Academies. I am now building on this to understand how brain wiring underpins function, and, again, the corpus callosum is the perfect model to reveal these fundamental principles.
Expertise
Techniques used in the lab include:
- Magnetic Resonance Imaging – diffusion tensor imaging (human and animal).
- In utero surgery, in utero and in pouch electroporation of genetic constructs to label cells, over-express genes, or knock-down protein expression by siRNA.
- Tissue culture and in vitro primary cultures, including organotypic slice culture.
- Neuroanatomical and histological approaches including tract tracing, immunohistochemistry, cryostat, vibratome, freezing microtome and electron and confocal microscopy.
- Two-photon microscopy of calcium imaging in the brain of early developing marsupials.
- Molecular biological and genomic approaches including RNA sequencing, quantitative PCR, northern and western blotting, in situ hybridisation, chromatin immunoprecipitation, luciferase assays and bioinformatic genomic analyses.
Publications (& Journals)
Research publications
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Edwards T.J., Fenlon L.R., Dean R.J., Bunt J., IRC5 Consortium, Sherr E.H. and Richards L.J. (2020) Altered structural connectivity networks in a mouse model of complete and partial dysgenesis of the corpus callosum NeuroImage doi.org/10.1016/j.neuroimage.2020.116868.
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Paolino A., Fenlon L.R., Kozulin P., Haines E., Lim J.W.C., Richards L.J. and Suárez R. (2020) Differential timing of a conserved transcriptional network underlies divergent cortical projection routes across mammalian evolution. Proc. Natl. Acad. Sci. USA Sciences doi.org/10.1073/pnas.1922422117.
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Chen K-S., Bunt J., Bridges C.R., Lynton Z., Lim J.W.C., Stringer B.W., Rajagopal R., Wong K-T., Ganesan D., Ariffin H., Day B.W., Richards L.J.§ and Bunt J.§ (2019) Transcription factors NFIA and NFIB induce cellular differentiation high-grade astrocytoma. Journal of Neuro-Oncology doi:10.1007/s11060-019-03352-3. §Equal last and senior authors.
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Schanze I., Bunt J., Boppudi S., Lim J.W.C., Schanze D., Dean R.J., Alders M., Blanchet P., Attié-Bitach T., Berland S., Bridges C.J., Cho M.T., Desai S., Dobyns W.B., Donnai D., Douglas J., Earl D.L., Edwards T.J., Faivre L., Genevieve D., Gérard M., Gatinois V., Holder-Espinasse M., Huth S.F., Izumi, K., Kerr, B., Lacaze E., Lakeman P., Mirzaa G., Morgan S., Nowak C., Peeters H., Petit F., Pilz D.T., Puechberty J., Reinstein E., Rivière J-B., Santani A.B., Schneider A., Sherr E.H., Smith-Hicks C., Wieland I., Zackai E., Zhao X., Gronostajski R.M., Zenker M., and Richards L.J. (2018) NFIB haploinsufficiency is associated with intellectual disability and marcocephaly. The American Journal of Human Genetics doi: 10.1016/j.ajhg.2018.10.006.
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Suárez R., Paolino A., Fenlon L.R., Morcom L.R., Kozulin P., Kurniawan N.D., and Richards L.J. (2018) A pan-mammalian map of interhemispheric brain connections predates the evolution of the corpus callosum. Proc. Natl. Acad. Sci. USA Sciences doi.org/10.1073/pnas.1808262115.
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Hearne L.J., Dean R., Robinson G., Richards L.J., Mattingley J. and Cocchi L. (2018) Increased cognitive complexity reveals abnormal brain network activity in individuals with corpus callosum dysgenesis. Neuroimage: Clinical doi.org/10.1016/j.nicl.2018.11.005.
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Marsh A.P.L., Herron D., Edwards T.J., et al, Richards L.J.§ Lockhart P.J.§ and Depienne C.§ (2017) Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance. Nature Genetics doi:10.1038/ng.3794. §Equal last and senior authors.
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Gobius I., Morcom L., Suárez R., Bunt J., Bukshpun P., Reardon W., Dobyns W.B., Rubenstein J.L.R., Barkovich A.J., Sherr E.H. and Richards L.J. (2016) Astroglial-mediated remodeling of the interhemispheric midline is required for the formation of the corpus callosum. Cell Reports 17: 735-747. doi.org/10.1016/j.celrep.2016.09.033.
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Stringer B.W., Bunt J., Bryan W., Day B.W., Barry G., Jamieson P.R., Ensbey K.S., Bruce Z.C., Goasdoué K., Vidal H., Charmsaz S., Smith F.M., Cooper L.T., Piper M., Boyd A.W. and Richards L.J. (2016) Nuclear Factor One B (NFIB) encodes a subtype-specific tumour suppressor in glioblastoma. Oncotarget 5. 2016 May 17;7(20):29306-20. doi: 10.18632/oncotarget.8720.
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Suárez R., Fenlon L.R., Marek R., Avitan L., Sah P., Goodhill G.J. and Richards L.J. (2014) Balanced interhemispheric cortical activity is required for correct targeting of the corpus callosum. Neuron 82: 1289-1298. doi.org/10.1016/j.neuron.2014.04.040.
Publications in Neuroscience Advocacy
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International Brain Initiative (IBI) (2020) International Brain Initiative: An innovative framework for coordinated global brain research efforts. Neuron doi:10.1016/j.neuron.2020.01.002. * Richards L.J. co-corresponding author.
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Australian Brain Alliance (2019) A Neuroethics Framework for the Australian Brain Initiative. Neuron doi: 10.1016/j.neuron.2019.01.004. *Richards L.J. co-corresponding author.
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Australian Brain Alliance (2016) Australian Brain Alliance Neuron 92: 597-600. doi.org/10.1016/j.neuron.2016.10.038. *Richards L.J. corresponding author.