Anna La Torre, Ph.D.
The Central Nervous System (CNS) is a complex network of numerous cell types. For example the human brain contains about 80 billion neurons associated with roughly 300 billion glial cells, and hundreds of different neuronal and glial cell types have been identified by morphology alone. Understanding how this myriad of different cell populations is generated is a fundamental question in neurobiology but also can potentially lead to novel stem cell-based therapies for a diverse array of neurodegenerative diseases.
All the cell lineages of the CNS are derived from a common pool of multipotent progenitors. Neuronal progenitor cells are intrinsically limited such that a particular progenitor can only differentiate into a subset of cell types at a given time during development. A broadly accepted model proposes that progenitor cells progressively change their competence to generate different cell populations as development proceeds.
The goal of our research is to decipher the cellular and molecular mechanisms underlying neuronal progenitor competence and differentiation using a combination of cell lines, transgenic mouse models and biochemical approaches. We use the retina as a model system due to its relatively simple cytoarchitecture and high accessibility.
Some of the projects that we are currently pursuing in the laboratory are:
- Role of microRNAs in the dynamic regulation of progenitor competence during retinal histogenesis.
- Mechanisms of cone photoreceptor fate determination.
- Early retinal specification and eye field formation.
Additionally, the retina can be affected by a number of diseases that lead to progressive cell loss and ultimately irreversible blindness. These devastating conditions affect millions of people worldwide. Recently, advances in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) technologies have raised the possibility of custom-built cells for in vitro studies, drug screening and cell replacement therapies. In this direction, our group has successfully differentiated ESCs and iPSCs into a variety of retinal cell types including photoreceptors and Retinal Ganlgion Cells.
See: An updated list of current publications on “Google Scholar” »
Miltner AM, La Torre A. “Retinal Ganglion Cell Replacement: Current Status and Challenges Ahead”. Dev Dyn. September 21 (2018)
Fairchild CL, Hino K, Han JS, Miltner AM, Peinado Allina G, Brown CE, Burns ME, La Torre A*, Simó S*. “RBX2 maintains final retinal cell position in a DAB1-dependent and -independent fashion”. Development. Feb 2 (2018) *Co-senior authors
Akina Hoshino, Rinki Ratnapriya, Matthew J. Brooks, Vijender Chaitankar, Matthew S. Wilken, Chi Zhang, Margaret R. Starostik, Linn Gieser, Anna La Torre, Mario Nishio, Olivia Bates, Ashley Walton, Olivia Bermingham-McDonogh, Ian A. Glass, Rachel O.L. Wong, Anand Swaroop, Thomas A. Reh. “Molecular Anatomy of the Developing Human Retina”. Developmental Cell. December 18 (2017)
La Torre A. “Retinal Differentiation of Mouse Embryonic Stem Cells”. Bio-protocol 2016 6(13): e1851. DOI: 10.21769/BioProtoc.1851. 2016
La Torre A, Hoshino A, Cavanaugh C, Ware CB, Reh TA. “The GIPC1-Akt1 Pathway Is Required for the Specification of the Eye Field in Mouse Embryonic Stem Cells”. Stem Cells. 2015 May 26. PMID: 26013465
Zhang J, Taylor RJ, La Torre A, Wilken MS, Cox KE, Reh TA, Vetter ML. “Ezh2 maintains retinal progenitor proliferation, transcriptional integrity, and the timing of late differentiation”. Dev Biol. 2015 Jul 15;403(2):128-38. doi: 10.1016/j.ydbio.2015.05.010. Epub 2015 May 16. PMID: 25989023
Wilken M.S., Brzezinski J.A., La Torre A., Sabo P.; Canfield T.; Thurman R.; Siebenthall K.; Sandstrom R.; Vierstra J.; Stamatoyannopoulos J.; Reh T.A. “Genome-wide DNase1 mapping of developing retina identifies a large number of potential cis-regulatory elements for stage and cell-type specific gene expression”. Epigenetics Chromatin. 2015 Feb 28;8:8. doi: 10.1186/1756-8935-8-8. eCollection 2015. PMID: 25972927
La Torre A.; Georgi S.A. and Reh T.A. “A conserved miRNA pathway regulates developmental timing of retinal neurogenesis”. Proc Natl Acad Sci U S A. Jun 10 (2013). PMID: 23754433
La Torre A.; Masdeu M.; Cotrufo T; Moubarak R.S.; del Río J.A.; Comella J.X.; Soriano E. and Urena J.M. “A role for the tyrosine kinase Ack1 in Neurotrophin Signaling and Neuronal Extension and branching”. Cell Death Dis. April 18 (2013). PMID: 23598414
La Torre A.; Lamba D.A.; Jayabalu A. and Reh T.A. “Production and transplantation of retinal cells from human and mouse embryonic stem cells”. Methods Mol. Biol. (2012). PMID: 22688710
Quintana A.; Sanz E.; Wang W.; Storey G.P.; Güler A.D.; Wanat M.J.; Roller B.A.; La Torre A.; Amieux P.S.; McKnight G.S.; Bamford N.S and Palmiter R.D. “Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors”. Nat Neurosci. October 14 (2012). PMID: 23064379
Simó, S., Pujadas L., Segura M.F., La Torre A., Del Rio J.A., Urena J.M., Comella J. X., and Soriano E. (2007). “Reelin induces the detachment of postnatal subventricular zone cells and the expression of the Egr-1 through Erk1/2 activation”. Cereb Cortex. 17:294-303.
La Torre A.; Del Río J.A.; Soriano E. and Ureña J.M. “Expression pattern of Ack1 during brain development in mouse”. Gene Expression Patterns, May 31 (2006). PMID: 16750431
Ureña J.M.; La Torre A.; Martínez A.; Lowenstein E.; Franco N.; Winsky-Sommerer R.; Fontana X.; Casaroli R.; Ibáñez M.A.; Pascual M.; Del Río J.A.; de Lecea L. and Soriano E. “Expression, synaptic localization and developmental regulation of Ack1/Pyk1: a cytoplasmic tyrosine kinase highly expressed in adult and developing brain”. Journal of Comparative Neurology 490, 119-132 (2005). PMID: 16052498
Gonzalez-Billault, C., Del Rio J.A., Urena J.M., Jimenez-Mateos E.M., Barallobre M.J., Pascual M., Pujadas L., Simó S., La Torre A., Gavin R., Wandosell F., Soriano E., and J. Avila J. (2005). “A role of MAP1B in Reelin-dependent neuronal migration”. Cereb Cortex. 15:1134-45.
Del Rio, J.A., Gonzalez-Billault C., Urena J.M., Jimenez E.M., Barallobre M.J., Pascual M., Pujadas L., Simó S., La Torre A., Wandosell F., Avila J., and Soriano E. (2004). “MAP1B is required for Netrin 1 signaling in neuronal migration and axonal guidance”. Curr Biol. 14:840-50.