![Branko Latinkic](https://profiles-cardiff.imgix.net/attachments/1093?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Dr Branko Latinkic
Reader
- Available for postgraduate supervision
School of Biosciences
Overview
We study the molecular and cellular mechanisms of early heart development in vertebrates, with particular focus on cardiac specification and differentiation. Our long-standing model for these studies has been the frog (Xenopus) embryo. Recently we have complemented this in vivo model by human iPS cells, which can be readily differentiated into cardiomyocytes to provide an excellent in vitro model of cardiogenesis.
Publication
2019
- Haworth, K., Samuel, L., Black, S., Kirilenko, P. and Latinkic, B. 2019. Liver specification in the absence of cardiac differentiation revealed by differential sensitivity to Wnt/β catenin pathway activation. Frontiers in Physiology 10, article number: 155. (10.3389/fphys.2019.00155)
2016
- Caporilli, S. and Latinkic, B. 2016. Ventricular cell fate can be specified until the onset of myocardial differentiation. Mechanisms of Development 139, pp. 31-41. (10.1016/j.mod.2016.01.001)
2015
- Freeman, J. et al. 2015. A functional connectome: regulation of Wnt/TCF-dependent transcription by pairs of pathway activators. Molecular Cancer 14, article number: 206. (10.1186/s12943-015-0475-1)
2014
- Gallagher, J. M. et al. 2014. Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4. Mechanisms of Development 134, pp. 31-41. (10.1016/j.mod.2014.09.001)
- Yamak, A., Latinkic, B. V., Dali, R., Temsah, R. and Nemer, M. 2014. Cyclin D2 is a GATA4 cofactor in cardiogenesis. Proceedings of the National Academy of Sciences 111(4), pp. 1415-1420. (10.1073/pnas.1312993111)
2012
- Gallagher, J. M., Komati, H., Roy, E., Nemer, M. and Latinkic, B. 2012. Dissociation of cardiogenic and postnatal myocardial activities of GATA4. Molecular and Cellular Biology 32(12), pp. 2214-2223. (10.1128/MCB.00218-12)
2010
- Ewan, K. B. R. et al. 2010. A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription. Cancer Research 70(14), pp. 5963-5973. (10.1158/0008-5472.CAN-10-1028)
2009
- Samuel, L. and Latinkic, B. 2009. Early activation of FGF and Nodal pathways mediates cardiac specification independently of Wnt/β-catenin signaling. PLoS ONE 4(10), article number: e7650. (10.1371/journal.pone.0007650)
- Walters, Z. S., Haworth, K. and Latinkic, B. 2009. NKCC1 (SLC12a2) induces a secondary axis in Xenopus laevis embryos independently of its co-transporter function. Journal of Physiology 587(3), pp. 521-529. (10.1113/jphysiol.2008.161562)
- Haworth, K. E. and Latinkic, B. 2009. Expression of Xenopus tropicalis HNF6/Onecut-1. International Journal of Developmental Biology 53(1), pp. 159-162. (10.1387/ijdb.072472ke)
2008
- Haworth, K., Kotecha, S., Mohun, T. J. and Latinkic, B. V. 2008. GATA4 and GATA5 are essential for heart and liver development in Xenopus embryos. BMC Developmental Biology 8, article number: 74. (10.1186/1471-213X-8-74)
2006
- Smith, S. J., Fairclough, L., Latinkic, B., Sparrow, D. B. and Mohun, T. J. 2006. Xenopus laevis transgenesis by sperm nuclear injection. Nature Protocols 1(5), pp. 2195-2203. (10.1038/nprot.2006.325)
2004
- Mercurio, S., Latinkic, B., Itasaki, N., Krumlauf, R. and Smith, J. C. 2004. Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex. Development 131(9), pp. 2137-2147. (10.1242/dev.01045)
- Latinkic, B., Cooper, B., Smith, S., Kotecha, S., Towers, N., Sparrow, D. and Mohun, T. J. 2004. Transcriptional regulation of cardiac-specific MLC2 gene during Xenopus embryonic development. Development 131, pp. 669-679. (10.1242/dev.00953)
2003
- Latinkic, B., Kotecha, S. and Mohun, T. J. 2003. Induction of cardiomyocytes by GATA4 in Xenopus ectodermal explants. Development 130, pp. 3865-3876. (10.1242/dev.00599)
- Latinkic, B. et al. 2003. Xenopus Cyr61 regulates gastrulation movements and modulates Wnt signalling. Development 130, pp. 2429-2441. (10.1242/dev.00449)
2002
- Smith, S. J., Kotecha, S., Towers, N., Latinkic, B. and Mohun, T. J. 2002. XPOX2-peroxidase expression and the XLURP-1 promoter reveal the site of embryonic myeloid cell development in Xenopus. Mechanisms of Development 117(1-2), pp. 173-186. (10.1016/S0925-4773(02)00200-9)
- Latinkic, B., Towers, N. and Kotecha, S. 2002. Regulation of cardiac muscle differentiation in Xenopus laevis embryos. Cold Spring Harbor Symposia on Quantitative Biology 67, pp. 13-18. (10.1101/sqb.2002.67.13)
2001
- Latinkic, B. et al. 2001. Promoter function of the angiogenic inducer Cyr61gene in transgenic mice: tissue specificity, inducibility during wound healing, and role of the serum response element. Endocrinology 142(6), pp. 2549-2557. (10.1210/en.142.6.2549)
2000
- Lerchner, W., Latinkic, B., Remacle, J. E., Huylebroeck, D. and Smith, J. C. 2000. Region-specific activation of the Xenopus Brachyury promoter involves active repression in ectoderm and endoderm: A study using transgenic frog embryos. Development 127, pp. 2729-2739.
- Sparrow, D. B. et al. 2000. Regulation of the tinman homologues in xenopus embryos. Developmental Biology 227(1), pp. 65-79. (10.1006/dbio.2000.9891)
- Sparrow, D. B., Latinkic, B. and Mohun, T. J. 2000. A simplified method of generating transgenic Xenopus. Nucleic Acids Research 28(4), article number: e12. (10.1093/nar/28.4.e12)
Articles
- Haworth, K., Samuel, L., Black, S., Kirilenko, P. and Latinkic, B. 2019. Liver specification in the absence of cardiac differentiation revealed by differential sensitivity to Wnt/β catenin pathway activation. Frontiers in Physiology 10, article number: 155. (10.3389/fphys.2019.00155)
- Caporilli, S. and Latinkic, B. 2016. Ventricular cell fate can be specified until the onset of myocardial differentiation. Mechanisms of Development 139, pp. 31-41. (10.1016/j.mod.2016.01.001)
- Freeman, J. et al. 2015. A functional connectome: regulation of Wnt/TCF-dependent transcription by pairs of pathway activators. Molecular Cancer 14, article number: 206. (10.1186/s12943-015-0475-1)
- Gallagher, J. M. et al. 2014. Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4. Mechanisms of Development 134, pp. 31-41. (10.1016/j.mod.2014.09.001)
- Yamak, A., Latinkic, B. V., Dali, R., Temsah, R. and Nemer, M. 2014. Cyclin D2 is a GATA4 cofactor in cardiogenesis. Proceedings of the National Academy of Sciences 111(4), pp. 1415-1420. (10.1073/pnas.1312993111)
- Gallagher, J. M., Komati, H., Roy, E., Nemer, M. and Latinkic, B. 2012. Dissociation of cardiogenic and postnatal myocardial activities of GATA4. Molecular and Cellular Biology 32(12), pp. 2214-2223. (10.1128/MCB.00218-12)
- Ewan, K. B. R. et al. 2010. A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription. Cancer Research 70(14), pp. 5963-5973. (10.1158/0008-5472.CAN-10-1028)
- Samuel, L. and Latinkic, B. 2009. Early activation of FGF and Nodal pathways mediates cardiac specification independently of Wnt/β-catenin signaling. PLoS ONE 4(10), article number: e7650. (10.1371/journal.pone.0007650)
- Walters, Z. S., Haworth, K. and Latinkic, B. 2009. NKCC1 (SLC12a2) induces a secondary axis in Xenopus laevis embryos independently of its co-transporter function. Journal of Physiology 587(3), pp. 521-529. (10.1113/jphysiol.2008.161562)
- Haworth, K. E. and Latinkic, B. 2009. Expression of Xenopus tropicalis HNF6/Onecut-1. International Journal of Developmental Biology 53(1), pp. 159-162. (10.1387/ijdb.072472ke)
- Haworth, K., Kotecha, S., Mohun, T. J. and Latinkic, B. V. 2008. GATA4 and GATA5 are essential for heart and liver development in Xenopus embryos. BMC Developmental Biology 8, article number: 74. (10.1186/1471-213X-8-74)
- Smith, S. J., Fairclough, L., Latinkic, B., Sparrow, D. B. and Mohun, T. J. 2006. Xenopus laevis transgenesis by sperm nuclear injection. Nature Protocols 1(5), pp. 2195-2203. (10.1038/nprot.2006.325)
- Mercurio, S., Latinkic, B., Itasaki, N., Krumlauf, R. and Smith, J. C. 2004. Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex. Development 131(9), pp. 2137-2147. (10.1242/dev.01045)
- Latinkic, B., Cooper, B., Smith, S., Kotecha, S., Towers, N., Sparrow, D. and Mohun, T. J. 2004. Transcriptional regulation of cardiac-specific MLC2 gene during Xenopus embryonic development. Development 131, pp. 669-679. (10.1242/dev.00953)
- Latinkic, B., Kotecha, S. and Mohun, T. J. 2003. Induction of cardiomyocytes by GATA4 in Xenopus ectodermal explants. Development 130, pp. 3865-3876. (10.1242/dev.00599)
- Latinkic, B. et al. 2003. Xenopus Cyr61 regulates gastrulation movements and modulates Wnt signalling. Development 130, pp. 2429-2441. (10.1242/dev.00449)
- Smith, S. J., Kotecha, S., Towers, N., Latinkic, B. and Mohun, T. J. 2002. XPOX2-peroxidase expression and the XLURP-1 promoter reveal the site of embryonic myeloid cell development in Xenopus. Mechanisms of Development 117(1-2), pp. 173-186. (10.1016/S0925-4773(02)00200-9)
- Latinkic, B., Towers, N. and Kotecha, S. 2002. Regulation of cardiac muscle differentiation in Xenopus laevis embryos. Cold Spring Harbor Symposia on Quantitative Biology 67, pp. 13-18. (10.1101/sqb.2002.67.13)
- Latinkic, B. et al. 2001. Promoter function of the angiogenic inducer Cyr61gene in transgenic mice: tissue specificity, inducibility during wound healing, and role of the serum response element. Endocrinology 142(6), pp. 2549-2557. (10.1210/en.142.6.2549)
- Lerchner, W., Latinkic, B., Remacle, J. E., Huylebroeck, D. and Smith, J. C. 2000. Region-specific activation of the Xenopus Brachyury promoter involves active repression in ectoderm and endoderm: A study using transgenic frog embryos. Development 127, pp. 2729-2739.
- Sparrow, D. B. et al. 2000. Regulation of the tinman homologues in xenopus embryos. Developmental Biology 227(1), pp. 65-79. (10.1006/dbio.2000.9891)
- Sparrow, D. B., Latinkic, B. and Mohun, T. J. 2000. A simplified method of generating transgenic Xenopus. Nucleic Acids Research 28(4), article number: e12. (10.1093/nar/28.4.e12)
Research
In vertebrates, cardiac precursors are specified during gastrulation, almost simultaneously with major developmental decisions that will shape the embryo. Because of this, it is challenging to directly investigate cardiac specification in vivo.
Our model of choice for studying early heart development is an ex vivo assay that allows experimental manipulation and features rapid and robust cardiac differentiation. It is based on pluripotent animal pole explants derived from blastula stage Xenopus embryos. In isolation these explants normally develop into epidermis, but can be converted into cardiomyocytes by activin/Nodal signalling or by cardiogenic transcription factor GATA4, in ~ 2 days post fertilisation. In addition, the Xenopus embryo model has well-established loss- and gain-of function approaches for studying gene function.
Cardiogenesis triggered by GATA4 in pluripotent ectodermal cells recapitulates normal course of cardiomyocyte differentiation as it occurs in vivo and represents a simple tractable model which has allowed us to investigate molecular determinants of cardiogenic activity of GATA4 as well as the key targets regulated by GATA4.
We have recently established in our group a model for human cardiogenesis based on induced Pluripotent State Cells (iPSCs). iPSCs can be efficiently differentiated into cardiomyocytes (iPSC-CMs), providing an accessible model for dissecting molecular mechanisms guiding human cardiac differentiation (see Figure for an example of iPSC-CMs generated in our group) . We are currently using the iPSC-CM model to verify GATA4 targets identified in Xenopus embryos. In collaboration with consultant cardiologist Zaheer Yousef we are also using iPSC-CMs to develop ‘disease in a dish’ models of hypertrophic cardiomyopathies using genetic information and somatic cells for generation of iPSCs from patients with established family pedigrees.
Current Funding
- British Heart Foundation
Collaborators
Prof. M. Nemer - Ottawa
Prof. Nick Allen – Cardiff
Prof. Chris Denning- Nottingham
Prof. Zaheer Yousef - Cardiff
Co-workers
Pavel Kirilenko
Nicola Graham
Gabrielle Evans
Beth Burgess
Biography
- 1987. BSc in molecular biology, Belgrade University.
- 1994. PhD in molecular genetics, University of Illinois at Chicago.
Regulation of mammalian immediate-early genes, the lab of Prof. Lester Lau. - 1995-1998. Postdoc with Dr. Jim Smith, National Institute for Medical Research, Mill Hill. Mechanisms of mesoderm induction.
- 1999-2003. Postdoc with Dr. Tim Mohun, National Institute for Medical Research, Mill Hill. Mechanisms of cardiac induction and gene expression.
- 2004- Lecturer in School of Biosciences, Cardiff University.
Contact Details
LatinkicB@cardiff.ac.uk
+44 29208 75784
Sir Martin Evans Building, Room Cardiff School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, Museum Avenue, Cardiff, CF10 3AX
+44 29208 75784
Sir Martin Evans Building, Room Cardiff School of Biosciences, The Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX, Museum Avenue, Cardiff, CF10 3AX