Professor Linda J. Richards - Cortical Development and Axon Guidance

Professor Linda Richards

 Contact Information

  richards@uq.edu.au
  Building: QBI Building #79
  Room: 434
  Tel: +61 7 334 66355

 Mailing Address

  Queensland Brain Institute
  The University of Queensland
  Brisbane, 4072
  Queensland,
  Australia

 Links

 Lab Members

 Lab Home Page

Short Biography

Research directions

Current collaborations

Selected publications

Short Biography

Professor Richards did her undergraduate degree at Monash University and obtained her BSc (Hons) and a PhD from The University of Melbourne and The Walter and Eliza Hall Institute in the laboratory of Prof. Perry Bartlett. Her thesis was on the determination of neuronal lineage in the developing spinal cord. She then moved to the USA to complete a postdoctoral fellowship at The Salk Institute for Biological Studies where she worked with Professor Dennis O’Leary on cortical development and formation of the lateral cortical projection through the internal capsule. She began her independent laboratory at The University of Maryland Medical School in 1997, in the Department of Anatomy and Neurobiology chaired by Professor Michael Shipley. In 2005 she moved her laboratory to The University of Queensland and was appointed as an Associate Professor in the Queensland Brain Institute and The School of Biomedical Sciences and in 2006, she was appointed as an NHMRC Senior Research Fellow. In 2010, she was promoted to Professor at The University of Queensland and promoted to NHMRC Principal Research Fellow in 2011. In addition to running her laboratory, Professor Richards is passionate about informing the public about science. In 2006 she founded the Australian Brain Bee Challenge, a program that inspires and excites high school students about science.

 

Research directions

 

Professor Richards' laboratory investigates how the brain becomes wired up during development. The lab is focusing on the development of the cerebral cortex, a region of the brain where all higher order cognition is processed. The lab investigates the development of the largest fibre tract in the brain, called the corpus callosum, that connects neurons in the left and right cerebral hemispheres. Professor Richards' lab is interested in the development of the cortical midline and aspects of glial and neuronal development that impact the formation of midline structures such as the corpus callosum. The lab utilises both mouse and human tissue in its projects and applies the results to identifying the basis of agenesis of the corpus callosum, a condition that occurs in more than 50 different human congenital syndromes.

Techniques used in the lab include:

  • Magnetic Resonance Imaging – diffusion tensor imaging.
  • In utero surgery, in utero 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
  • Molecular Biological approaches including protein purification, PCR, Northern, and Western Blotting, in situ hybridisation, chromatin immunoprecipitation, luciferase assays and genomic analysis

Join our team: Projects available for students at all levels of study from high school to PhD. Contact Prof. Richards for further details.

 

Current collaborations

  • Prof. Rich Gronostajski, SUNY, Buffalo, NY, USA.
  • Prof. Geoffrey Goodhill, The University of Queensland
  • Assoc. Prof. Elliott Sherr, University of California, San Francisco
  • Assoc. Prof. Shubha Tole, Tata Institute for Fundamental Research
  • Prof. John Rubenstein, University of California, San Francisco
     

Selected publications

 

Subramanian L, Sarkar A, Shetty AS, Muralidharan B, Padmanabhan H, Piper M, Monuki ES, Bach I, Gronostajski RM, Richards LJ, Tole S. (2011) Transcription factor Lhx2 is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus. Proc Natl Acad Sci U S A. [Epub ahead of print]

Moldrich RX, Mezzera C, Holmes WM, Goda S, Brookfield SJ, Rankin AJ, Barr E, Kurniawan N, Dewar D, Richards LJ, López-Bendito G, Iwata T. (2011) Fgfr3 regulates development of the caudal telencephalon. Dev Dyn. 240(6):1586-99. doi: 10.1002/dvdy.22636.

Thompson A., Pujic Z., RichardsLJ and Goodhill GJ. (2011) Cyclic nucleotide-dependent switching of mammalian axon guidance depends on gradient steepness. Mol. Cell. Neurosci. 47(1):45-52.

Chuang N, Mori S, Yamamoto A, Jiang H, Ye X, Xu X, Richards LJ, Nathans J, Miller MI, Toga AW, Sidman RL, and Zhang J. (2011) An MRI-based atlas and database of the developing mouse brain. Neuroimage. 54:80-9.

Moldrich RX, Gobius I, Pollak T, Zhang J, Ren T, Brown L, Mori S, De Juan Romero C, Britanova O, Tarabykin V, and Richards LJ. (2010) Molecular regulation of the developing commissural plate. J Comp Neurol. 518:3645-61.

Piper M, Barry G, Hawkins J, Mason S, Lindwall C, Little E, Sarkar A, Smith AG, Moldrich RX, Boyle GM, Tole S, Gronostajski RM, Bailey TL, and Richards LJ. (2010) NFIA controls telencephalic progenitor cell differentiation through repression of the Notch effector Hes1. J Neurosci. 30:9127-39.

Moldrich RX, Pannek K, Hoch R, Rubenstein JL, Kurniawan ND, and Richards LJ. (2010) Comparative mouse brain tractography of diffusion magnetic resonance imaging. Neuroimage. 51:1027-36.

Piper M, Moldrich R, Lindwall C, Little E, Barry G, Mason S, Sunn N, Kurniawan N, Gronostajski R and Richards LJ (2009) Multiple non-cell autonomous defects underlies neocortical callosal dysgenesis in Nfib-deficient mice. Neural Development 4;43.

Mortimer D, Feldner J, Vaughan T, Vetter I, Pujic Z, Rosoff WJ, Burrage K, Dayan P, Richards LJ, Goodhill GJ (2009) A Bayesian model predicts the response of axons to molecular gradients. Proc. Natl. Acad Sci. (USA), 106;10296-10301 (cover image).

Huang H., Xue R., Zhang J., Ren T., Richards L.J., Yarowsky P., Miller M., Mori S. (2009) Anatomical Characterization of Human Fetal Brain Development with Diffusion Tensor Magnetic Resonance Imaging. Journal of Neuroscience 29; 4263-73

M. Piper, C. Plachez, O. Zalucki, T. Fothergill, R. Erzurumlu, C. Gu, L.J. Richards (2009) Neuropilin1 regulates crossing of cingulate pioneering axons during development of the corpus callosum. Cerebral Cortex 19, Suppl 1:11-21.

A. Kumbasar, C. Plachez, R.M. Gronostajski, L.J. Richards, E.D Litwack (2009) Absence of the transcription factor Nfib delays the formation of the basilar pontine and other mossy fiber nuclei. Journal of Comparative Neurology 513: 98-112.

G. Barry, M. Piper, C. Lindwall, R. Moldrich, S. Mason, E. Little, A. Sarkar, S. Tole, R. M. Gronostajski, L.J. Richards (2008) Specific glial populations regulate hippocampal morphogenesis. Journal of Neuroscience 28: 12328-12340.

C.E. Campbell, M. Piper, C. Plachez, Y.T. Yeh, J.S. Baizer, J.M. Osinski, E.D. Litwack, L.J. Richards, R.M. Gronostajski (2008) The transcription factor Nfix is essential for normal brain development. BMC Developmental Biology 8: 52.

C. Plachez, W. Andrews, A. Liapi, B. Knoell, U. Dreacher, B. Mankoo, L. Zhe, E. Mambetisaeva, A. Annan, L. Bannister, J.G. Parnavelas, L.J. Richards, V. Sundaresan (2008) Robos are required for the correct targeting of retinal ganglion cell axons in the visual pathway of the brain. Molecular and Cellular Neuroscience 37: 719-730.

C. Plachez, C. Lindwall, N. Sunn, M. Piper, R.X. Moldrich, C.E. Campbell, J.M. Osinski, R.M. Gronostajski, L.J. Richards (2008) Nuclear factor one gene expression in the developing forebrain. Journal of Comparative Neurology 508: 385-401.

T.Ren, J. Zhang, C. Plachez, S. Mori, L.J. Richards (2007) Diffusion tensor magnetic resonance imaging and tract-tracing analysis of Probst bundle structure in Netrin-1 and DCC-deficient mice. Journal of Neuroscience 27:10345-10349

J. Zhang J., L.J. Richards, M.I. Miller, P. Yarowsky, P. van Zijl, S. Mori (2006) Characterization of mouse brain and its development using diffusion tensor imaging and computational techniques. Conference Proceedings: IEEE Engineering in Medicine and Biology Society 1: 2252-2255. (Refereed conference paper).

H. Huang, J. Zhang, S. Wakana, W. Zhang, T. Ren, L.J. Richards, P. Yarowsky, P. Donohue, E. Graham, P. van Zijl, S. Mori (2006) White and gray matter development in human fetal, newborn and pediatric brains. Neuroimage 33: 27-38.

W.Andrews, A. Liapi, C. Plachez, L. Camurri, J. Zhang, S. Mori, F.Murakami, J.G. Parnavelas, V.Sundaresan, L.J. Richards (2006) Robo1 regulates the development of major axon tracts and interneuron migration in the forebrain. Development 133: 2243-2252.

T. Ren, A. Anderson, W-B. Shen, H. Huang, C. Plachez, J. Zhang, S. Mori, S.L. Kinsman, L.J. Richards (2006) Imaging, anatomical and molecular analysis of callosal formation in the developing human fetal brain. Anatomical Record A 288:191-214. (Special Edition on Neural Development).

W-B. Shen, C. Plachez, A.S. Mongi, L.J. Richards (2006) Identification of candidate genes at the cortcioseptal boundary during development. Mechanics of Development, Gene Expression Patterns 6: 471-481.

J. Zhang, M.I. Miller, C. Plachez, L.J. Richards, P. Yarowksy, P. van Zijl, S. Mori (2005) Mapping postnatal mouse brain development with diffusion tensor microimaging. NeuroImage 26: 1042-1051.

J. Zhang, Y. Chen, M.I. Miller, C. Plachez, J.M. Hardwick, L.J. Richards, P. Yarowksy, P. van Zijl, S. Mori (2005) Magnetic resonance diffusion tensor microimaging reveals a role for Bcl-x in brain development and homeostasis. Journal of Neuroscience 25: 1881-1888.

G. Steele-Perkins, C. Plachez, K.G. Butz, G. Yang, C.J. Bachurski, S.L. Kinsman, E.D. Litwack, L.J. Richards, R.M. Gronostajski (2005) The transcription factor Nfib is essential for both lung maturation and brain development. Molecular and Cellular Biology 25: 685-698

W.J. Rosoff, J.S. Urbach, M.A. Esrick, R.G. McAllister, L.J. Richards, G.J. Goodhill (2004) A novel chemotaxis assay reveals the extreme sensitivity of axons to molecular gradients. Nature Neuroscience 7: 678-682. This article was featured as a “News and Views” article in the same issue and was recommended by members of the Faculty of 1000.

Reviews

 

Chedotal A and Richards LJ (2010) Wiring the mammalian brain. In: Wiring the brain: The biology of neuronal guidance. Eds: Kolodkin A. and Tessier-Lavigne, M. Cold Spring Harbor Laboratories Press 2(6):a001917

Donahoo ALS and Richards LJ (2009) Understanding the mechanisms of callosal development through the use of transgenic mouse models. Sem. Ped. Neurol. 16: 127-142.

McGrath JJ, Richards LJ (2009). Why schizophrenia epidemiology needs neurobiology – and vice versa. Schizophrenia Bulletin doi: 10.1093/schbul/sbp004: 1-5.

S. Mason, M. Piper, R.M. Gronostajski, L.J. Richards (2009) Nuclear factor one transcription factors in CNS development. Molecular Neurobiology 39: 10-23.

D. Mortimer, T. Fothergill, Z. Pujic, L.J. Richards, G.J. Goodhill (2008) Growth cone chemotaxis. Trends in Neurosciences 31: 90-98.

C. Lindwall, T. Fothergilll, L.J. Richards (2007) Commissure formation in the mammalian forebrain. Current Opinion in Neurobiology 17: 3-14.

L.K. Paul, W.S. Brown, R. Adolphs, J.M. Tyszka, L.J.Richards, P. Mukherjee, and E.H. Sherr (2007) Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity. Nature Reviews Neuroscience 8: 287-299.

M. Piper, A.L.S. Dawson, C, Lindwall, G. Barry, C. Plachez, L.J. Richards (2007) Emx and Nfi genes regulate cortical development and axon guidance in the telencephalon Novartis Foundation Symposium (Cortical Development: Genes and Genetic Abnormalities) 288: 230-242.

C. Plachez, L.J. Richards (2005) Mechanisms of axon guidance in the developing nervous system. Current Topics in Developmental Biology 69: 267-346.

L.J. Richards, C. Plachez, T. Ren (2004) Mechanisms regulating the development of the corpus callosum and its agenesis in mouse and human. Clinical Genetics 66: 276-289.

L.J. Richards (2002). Surrounded by Slit – How forebrain axons can be led astray. Neuron 33: 153-158.

L.J. Richards (2002). Axonal pathfinding mechanisms at the cortical midline and in the development of the corpus callosum. Braz. J. Med. Biol. Res. 35: 1431-1439.

 


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