Professor Susan Lindsay
Prof of Human Dev Genetics
- Email: email@example.com
- Telephone: +44 (0) 191 241 8656
- Fax: +44 (0) 191 241 8666
- Personal Website: http://www.HuDSeN.org
- Address: Institute of Genetic Medicine
International Centre for Life
Newcastle upon Tyne
Gene expression studies during early human development
New technologies are enabling data to be collected on an unprecedented scale and making feasible a renewed focus on gene function, crucial 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.
My main research interest is in prenatal human brain development, particularly during the embryonic and early fetal stages. We are analysing gene expression patterns directly during human development both as part of specific projects and also on behalf of registered users of the MRC-Wellcome Trust Human Developmental Biology Resource (HDBR; www.hdbr.org). The HDBR is a tissue bank of human embryonic and fetal tissues, for which I am the Director in Newcastle and Prof Andrew Copp is the Director of the London site at the Institute of Child Health, UCL.
The human brain develops initially from a simple tube to a complex, highly organised three-dimensional (3D) structure with unique cognitive functions. In pioneering studies, we have generated 3D models of early human development onto which we are mapping gene expression patterns and defining anatomical features. These form the basis of the HuDSeN (Human Developmental Studies Network) Atlas and human gene expression spatial database (HuDSeN GXD; www.hudsen.org), now part of HDBR. HDBR’s HuDSeN GXD developed from the EMAGE database in collaboration with Professor Richard Baldock and his colleagues in the Edinburgh Mouse Atlas Project (http://www.emouseatlas.org/emap/home.html). Prof Luis Puelles’ and his colleagues at the University of Murcia (http://murcia.academia.edu/LuisPuelles) were instrumental in the anatomical delineations of early brain regions in the 3D models.
In collaboration with Dr Gavin Clowry (Institute of Neuroscience, http://www.ncl.ac.uk/ion/staff/profile/gavinclowry.html#background), we are studying the early development and function of the cortex.
Recently, a collaboration has been established with Prof Muzlifah Hanifa (Newcastle University) and Dr Sarah Teichmann who co-lead the Human Fetal Cell Atlas project (https://www.humancellatlas.org/areas-of-impact), an exciting new part of the Human Cell Atlas, which aims to generate a single cell atlas of tissues across developmental stages.
Dr Steven Lisgo, Senior Research Associate
Dr Janet Kerwin, Senior Research Associate
Dr Yuzhu Cheng, Research Associate
Moira Crosier, Research Associate
Jacqui Dobor, Group Secretary
Lynne Overman, Research Associate
Project led by Dr Gavin Clowry:
Ayman Alzu’Bi (PhD student)
- Lindsay SJ, Xu YB, Lisgo SN, Harkin LF, Copp AJ, Gerrelli D, Clowry GJ, Talbot A, Keogh MJ, Coxhead J, Santibanez-Koref M, Chinnery PF. HDBR Expression: A Unique Resource for Global and Individual Gene Expression Studies during Early Human Brain Development. Frontiers in Neuroanatomy 2016, 10, 86.
- Alzubi A, Lindsay S, Kerwin J, Looi SJ, Khalil F, Clowry GJ. Distinct cortical and sub-cortical neurogenic domains for GABAergic interneuron precursor transcription factors NKX2.1, OLIG2 and COUP-TFII in early fetal human telencephalon. Brain Structure and Function 2017, 222(5), 2309–2328.
- Harkin LF, Lindsay SJ, Xu Y, Alzu'bi A, Ferrara A, Gullon EA, James OG, Clowry GJ. Neurexins 1–3 Each Have a Distinct Pattern of Expression in the Early Developing Human Cerebral Cortex. Cerebral Cortex 2017, 27(1), 216-232.
- Gerrelli D, Lisgo S, Copp AJ, Lindsay S. Enabling research with human embryonic and fetal tissue resources. Development 2015, 142(18), 3073-3076.
- Al-Jaberi N, Lindsay S, Sarma S, Bayatti N, Clowry GJ. The Early Fetal Development of Human Neocortical GABAergic Interneurons. Cerebral Cortex 2015, 25(3), 631-645.
- 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 2012, 8(1), 210-223.
- Cheng YZ, Eley L, Hynes AM, Overman LM, Simms RJ, Barker A, Dawe HR, Lindsay S, Sayer JA. Investigating Embryonic Expression Patterns and Evolution of AHI1 and CEP290 Genes, Implicated in Joubert Syndrome. PloS One 2012, 7(9), e44975.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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<br>Issn: 0-122-20442-5<br>(Book) 1997.
- Chavali PL, Stojic L, Meredith LW, Joseph N, Nahorski MS, Sanford TJ, Sweeney TR, Krishna BA, Hosmillo M, Firth AE, Bayliss R, Marcelis CL, Lindsay S, Goodfellow I, Woods CG, Gergely F. Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication. Science 2017, 357(6346), 83-88.
- Alzu'bi A, Lindsay SJ, Harkin LF, McIntyre J, Lisgo SN, Clowry GJ. The Transcription Factors COUP-TFI and COUP-TFII have Distinct Roles in Arealisation and GABAergic Interneuron Specification in the Early Human Fetal Telencephalon. Cerebral Cortex 2017, epub ahead of print.