Newcastle University

Research Interests

Gene expression studies during early human development

As the sequencing of the human genome is now largely completed, the focus has shifted to trying to identify gene function. This is especially important for the large number of genes that play a role in human genetic disorders. One very important aspect of this work is to characterise gene expression patterns. Although animal models provide very powerful ways of studying normal and abnormal development, there are significant differences between humans and animals.

We are analysing gene expression patterns directly during human development both as part of specific projects (see below) and also on behalf of registered users of the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR; www.hdbr.org)

The human brain develops initially from a simple tube to a complex, highly organised three-dimensional (3-D) structure with unique cognitive functions. In pioneering studies, we have generated 3-D models of early human development onto which we are mapping gene expression patterns and defining anatomical features. Funded by the US National Institutes of Health and the EU, these now form the basis of a spatial gene expression database and anatomical atlas of the developing human brain that can be found at www.hudsen.org. HUDSEN, the Human Developmental Studies Network, arose from an EU FP6 Design Study (Developmental Gene Expression Map [DGEMap]; www.dgemap.org) and aims to bring together the biological, technological, informatics and ethics resources needed to define and analyse human developmental gene expression patterns. This is the first international network covering this field.

The HUDSEN human spatial gene expression database and anatomical atlas of the developing human brain is a collaborative project between the Human Developmental Genetics Group at the Institute of Human Genetics, (headed by Susan Lindsay and Tom Strachan), the Edinburgh Mouse Atlas Project (genex.hgu.mrc.ac.uk/; headed by Richard Baldock and Duncan Davidson) and Prof Luis Puelles’ group at the University of Murcia. The project is funded as a component within the NIH Human Brain Project.

In collaboration with Prof Janet Eyre and Dr Gavin Clowry in Child Health (Newcastle University), we are studying the development and function of the motor system, both in normal conditions and in relation to cerebral palsy, over a more extensive period of development.

Co-workers

Janet Kerwin BSc, PhD
Senior Research Associate
Subrot Sarma BSc MSc, PhD
Research Associate
Xunxian Wang BSc PhD
Senior Research Associate

Co-workers on collaborative projects:

With Dr Gavin Clowry

Nadhim Bayatti BSc PhD
Research Associate
Nahidh Al-Jaberi
Ph.D student
Beca Ip
PhD student

With Prof Deb Henderson, Dr Bill Chaudhry,
Prof Steve Robson, Prof Bob Anderson

Alina Andras BSc PhD
Research Associate
Darren Hoyland, PhD
Research Associate

• Lako M, Lindsay S, Lincoln J, Cairns PM, Armstrong L, Hole N. Characterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: Role of Wnt3 in enhancing haematopoietic differentiation. Mechanisms of Development 2001, 103(1-2), 49-59.
• Ip BK, Bayatti N, Howard NJ, Lindsay S, Clowry GJ. [abstract] Graded expression patterns of ROBO1, SRGAP1 and CTIP2 reveal early evidence of an anterior location of the motor cortex during fetal human development. Journal of Anatomy 2011, 218(3), 349.
• Sarma S, Thompson J, Kerwin J, Lindsay S. [abstract] Identification and characterisation of the rostral signaling center Anterior Neural Ridge during Early Human cortical Development. Journal of Anatomy 2011, 218(3), 355-355.
• Kerwin J, Hill B, Yang Y, Merchan P, Sandoval J, Sarma S, Baldock R, Puelles L, Lindsay S. [abstract] The HUDSEN Atlas: A new resource for studying morphogenesis and gene expression during human embryonic development. Journal of Anatomy 2011, 218(3), 354-355.
• Ali H, Forraz N, McGuckin C, Jurga M, Lindsay S, Ip BK, Trevelyan A, Basford C, Habibollah S, Ahmad S, Clowry GJ, Bayatti N. In vitro modelling of cortical neurogenesis by sequential induction of human umbilical cord blood stem cells. Stem Cell Reviews and Reports 2011, (epub ahead of print).
• Thomas MG, Crosier M, Lindsay S, Kumar A, Thomas S, Araki M, Talbot CJ, McLean RJ, Surendran M, Taylor K, Leroy BP, Moore AT, Hunter DG, Hertle RW, Tarpey P, Langmann A, Lindner S, Brandner M, Gottlob I. The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus. Brain 2011, 134(3), 892-902.
• Ip BK, Bayatti N, Howard NJ, Lindsay S, Clowry GJ. The Corticofugal Neuron-Associated Genes ROBO1, SRGAP1, and CTIP2 Exhibit an Anterior to Posterior Gradient of Expression in Early Fetal Human Neocortex Development. Cerebral Cortex 2011, 21(6), 1395-1407.
• Bakircioglu M, Carvalho OP, Khurshid M, Cox JJ, Tuysuz B, Barak T, Yilmaz S, Caglayan O, Dincer A, Nicholas AK, Quarrell O, Springell K, Karbani G, Malik S, Gannon C, Sheridan E, Crosier M, Lisgo SN, Lindsay S, Bilguvar K, Gergely F, Gunel M, Woods CG. The Essential Role of Centrosomal NDE1 in Human Cerebral Cortex Neurogenesis. American Journal of Human Genetics 2011, 88(5), 523-535.
• Wang WZ, Hoerder-Suabedissen A, Oeschger FM, Bayatti N, Ip BK, Lindsay S, Supramaniam V, Srinivasan L, Rutherford M, Mollgard K, Clowry GJ, Molnar Z. Subplate in the developing cortex of mouse and human. Journal of Anatomy 2010, 217(4), 368-380.
• Kerwin J, Yang YY, Merchan P, Sarma S, Thompson J, Wang XX, Sandoval J, Puelles L, Baldock R, Lindsay S. The HUDSEN Atlas: a three-dimensional (3D) spatial framework for studying gene expression in the developing human brain. Journal of Anatomy 2010, 217(4), 289-299.
• Nicholas A, Khurshid M, Désir J, Carvalho O, Cox J, Thornton G, Kausar R, Ansar M, Ahmad W, Verloes A, Passemard S, Misson J, Lindsay S, Gergely F, Dobyns W, Roberts E, Abramowicz M, Woods C. WDR62 is associated with the spindle pole and is mutated in human microcephaly. Nature Genetics 2010, 42(11), 1010-1014.
• Gerrelli D, Lisgo S, Copp A, Lindsay S. Human Developmental Biology Resource (HDBR): A unique resource for studying human embryo and fetal development. In: Mechanisms of Development: 16th Annual Conference of the International Society of Development Biologists. 2009, Edinburgh, Scotland: Elsevier.
• Bayatti N, Moss JA, Sun L, Ambrose P, Ward JFH, Lindsay S, Clowry GJ. A molecular neuroanatomical study of the developing human neocortex from 8 to 17 postconceptional weeks revealing the early differentiation of the subplate and subventricular zone. Cerebral Cortex 2008, 18(7), 1536-1548.
• Ip BK, Bayatti N, Lindsay S, Clowry GJ. Development of functional regionalization in the human neocortex: preliminary findings of SLIT/ROBO/srGAP differential expression. In: Summer Meeting of the Anatomical Society of Great Britain and Ireland. 2008, Jubilee Campus, University of Nottingham, UK: Journal of Anatomy: Wiley-Blackwell Publishing Ltd..
• Miyake N, Chilton J, Psatha M, Cheng L, Andrews C, Chan W-M, Law K, Crosier M, Lindsay S, Cheung M, Allen J, Gutowski NJ, Ellard S, Young E, Iannaccone A, Appukuttan B, Stout JT, Christiansen S, Ciccarelli ML, Baldi A, Campioni M, Zenteno JC, Davenport D, Mariani LE, Sahin M, Guthrie S, Engle EC. Human CHN1 mutations hyperactivate α2-chimaerin and cause Duane's retraction syndrome. Science 2008, 321(5890), 839-843.
• Bayatti N, Sarma S, Shaw C, Eyre JA, Vouyiouklis DA, Lindsay S, Clowry GJ. Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development. European Journal of Neuroscience 2008, 28(8), 1449-1456.
• Zappaterra MD, Lisgo SN, Lindsay S, Gygi SP, Walsh CA, Ballif BA. A comparative proteomic analysis of human and rat embryonic cerebrospinal fluid. Journal of Proteome Research 2007, 6(9), 3537-3548.
• Cantagrel V, Lossi A-M, Lisgo S, Missirian C, Borges A, Philip N, Fernandez C, Cardoso C, Figarella-Branger D, Moncla A, Lindsay S, Dobyns WB, Villard L. Truncation of NHEJ1 in a patient with polymicrogyria. Human Mutation 2007, 28(4), 356-364.
• Sarma S, Kerwin J, Puelles L, Scott M, Strachan T, Feng G, Sharpe J, Davidson D, Baldock R, Lindsay S. 3D modelling, gene expression mapping and post-mapping image analysis in the developing human brain. In: Evolution and Development of Nervous Systems - Proceedings of the 4th European Conference on Comparative Neurobiology. 2005, Oxford: Brain Research Bulletin, Elsevier.
• Lindsay S, Sarma S, Martinez-De-La-Torre M, Kerwin J, Scott M, Luis Ferran J, Baldock R, Puelles L. Anatomical and gene expression mapping of the ventral pallium in a three-dimensional model of developing human brain. Neuroscience 2005. , 136(3), 625-632.
• Feng G, Burton N, Hill B, Davidson D, Kerwin JM, Scott M, Lindsay S, Baldock R. JAtlas View: A Java atlas-viewer for browsing biomedical 3D images and atlases. BMC Bioinformatics 2005, 6(47), 7.
• Lindsay S, Copp AJ. MRC-Wellcome Trust Human Developmental Biology Resource: Enabling studies of human developmental gene expression. Trends in Genetics 2005. ,21 11 586-590.
• Kerwin JM, Scott MK, Sharpe J, Puelles L, Robson SC, Martínez de la Torre M, Ferran JL, Feng G, Baldock R, Strachan T, Davidson D, Lindsay SJ. 3 dimensional modelling of early human brain development using optical projection tomography. BMC Neuroscience 2004, 5, 27.
• Tonkin ET, Smith M, Eichhorn P, Jones S, Imamwerdi B, Lindsay S, Jackson M, Wang T-J, Ireland M, Burn J, Krantz ID, Carr P, Strachan T. A giant novel gene undergoing extensive alternative splicing is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3. Human Genetics 2004,115 2 139-148.
• Lindsay S, Scott M, Sarma S, Woods H, Crosier M, Lisgo S, Kerwin J, Strachan T, Robson SC. Human developmental gene expression: an important link between disorder and understanding. In: Journal of Medical Genetics: British Human Genetics Conference. 2004, York, UK: BMJ Group.
• Issac A, Sarma S, Lindsay S, Strachan T, Robson SC. Stability of RNA in human embryos stored over long periods of time. In: Journal of the Society for Gynecologic Investigation: 51st Annual Meeting of the Society for Gynecologic Investigation. 2004, Houston, Texas, USA: Sage Publications, Inc.
• Tonkin E, Smith M, Eichhorn P, Jones S, Imamwerdi B, Jackson M, Lindsay S, Carter N, Wang TJ, Ireland M, Burn J, Krantz I, Strachan T. A giant gone encoding a developmentally regulated novel member of the M28 peptidase family is severed by a Cornelia de Lange-associated translocation breakpoint at 3q26.3. In: American Journal of Human Genetics: Annual Meeting of the American Society of Human Genetics. 2003, Los Angeles, California, USA: Cell Press.
• Klauck SM, Lindsay S, Beyer KS, Splitt M, Burn J, Poustka A. A mutation hot spot for nonspecific X-linked mental retardation in the MECP2 gene causes the PPM-X syndrome. American Journal of Human Genetics 2002, 70(4), 1034-1037.
• Braybrook C, Lisgo S, Doudney K, Henderson D, Marcano ACB, Strachan T, Patton MA, Villard L, Moore GE, Stanier P, Lindsay S. Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPx patients. Human Molecular Genetics 2002, 11(22), 2793-2804.
• Jones EA, Tosh D, Wilson DI, Lindsay S, Forrester LM. Hepatic differentiation of murine embryonic stem cells. Experimental Cell Research 2002,272 1 15-22.
• Lynch SA, Wang Y, Strachan T, Burn J, Lindsay S. Autosomal dominant sacral agenesis: Currarino syndrome. Journal of Medical Genetics 2000, 37(8), 561-566.
• Fougerousse F, Bullen P, Herasse M, Lindsay S, Richard I, Wilson D, Suel L, Durand M, Robson S, Abitbol M, Beckmann JS, Strachan T. Human-mouse differences in the embryonic expression patterns of developmental control genes and disease genes. Human Molecular Genetics 2000, 9(2), 165-173.
• Lako M, Lindsay S, Cairns PM, Lincoln J, Armstrong L, Hole N. Involvement of Wnt genes in early haematopoiesis and identification of Wnt3 as a regulator of haematopoietic commitment. In: BLOOD. 2000.
• Hagan DM, Ross AJ, Strachan T, Lynch SA, Ruiz-Perez V, Wang YM, Scambler P, Custard E, Reardon W, Hassan S, Muenke M, Nixon P, Papapetrou C, Winter RM, Edwards Y, Morrison K, Barrow M, Cordier-Alex MP, Correia P, Galvin-Parton PA, Gaskill S, Gaskin KJ, Garcia-Minaur S, Gereige R, Hayward R, Homfray T, McKeown C, Murday V, Plauchu H, Shannon N, Spitz L, Lindsay S. Mutation analysis anti embryonic expression of the HLXB9 currarino syndrome gene. American Journal of Human Genetics 2000, 66(5), 1504-1515.
• Hanley NA, Hagan DM, Clement-Jones M, Ball SG, Strachan T, Salas-Cortes L, McElreavey K, Lindsay S, Robson S, Bullen P, Ostrer H, Wilson DI. SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development. Mechanisms of Development 2000, 91(1-2), 403-407.
• Clement-Jones M, Schiller S, Rao E, Blaschke RJ, Zuniga A, Zeller R, Robson SC, Binder G, Glass I, Strachan T, Lindsay S, Rappold GA. The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome. Human Molecular Genetics 2000, 9(5), 695-702.
• N. A. Hanley, S. G. Ball, M. Clement-Jones, D. M. Hagan, T. Strachan, S. Lindsay, S. Robson, H. Ostrer, K. L. Parker and D. I. Wilson. Expression of steroidogenic factor 1 and Wilms' tumour 1 during early human gonadal development and sex determination. Mechanisms of Development 1999, 87, 175-180.
• Ross AJ, Ruiz-Perez V, Wang Y, Hagan D-M, Scherer S, Lynch SA, Lindsay S, Custard E, Belloni E, Wilson DI, Wadey R, Goodman F, Orstavik KH, Monclair T, Robson S, Reardon W, Burn J, Scambler P, Strachan T. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nature Genetics 1998. , 20(4), 358-361.
• Young C, Lindsay S, Vater R, Slater CR. An improved method for the simultaneous demonstration of mRNA and esterase activity at the human neuromuscular junction. Histochemical Journal 1998,30 1 7-11.
• R. Vater, C. Young, L. V. B. Anderson, S. Lindsay, D. J. Blake, K. E. Davies, R. Zuellig and C. R. Slater. Utrophin mRNA expression in muscle is not restricted to the neuromuscular junction. Molecular and Cellular Neuroscience 1998, 10, 229-242.
• Strachan T, Lindsay S, Wilson DI. Molecular Genetics of Early Human Development (A Volume in the Human Molecular Genetics Series). Pub Academic Press. ISBN 0-122-20442-5
  Issn: 0-122-20442-5
  (Book) 1997.
• R. Vater, C. Young, S. J. Lindsay, L. V. B. Anderson and C. R. Slater. Distribution of utrophin mRNA in rat skeletal muscle. Journal of General Physiology 1996, 108, 80-80.
• Bryce, S.D., Lindsay, S., Gladstone, A.J., Braithwaite, K., Chapman, C., Spurr, N.K., Lunec, J. A novel family of cathespin L-like (CTSLL) sequences on human-chromosome 10Q and related transcripts. Genomics 1994, 24(3), 568-576.