Anna La Torre Villa, Ph.D.

 Anna  La Torre Villa, Ph.D.

Position

  • Assistant Professor
  • Cell Biology and Human Anatomy

Molecular mechanisms of Stem Cell Specification and Differentiation in the Retina

Research Summary

Molecular Mechanisms of Stem Cell Differentiation in the Central Nervous System

All the cells of the Central Nervous System are derived from a common pool of neuronal stem cells. Neuronal progenitors 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 mouse 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: 1) Role of microRNAs in the dynamic regulation of progenitor competence during retinal histogenesis. 2) Mechanisms of cone photoreceptor fate determination and 3) 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 human embryonic stem cell (hESC) 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 hESC and iPSCs into a variety of retinal cell types.  Currently, we are implementing novel strategies to differentiate ESCs into photoreceptors and Retinal Ganlgion Cells for cell replacement therapies.

Selected Publications

Anna La Torre. Retinal Differentiation of Mouse Embryonic Stem Cells. Bio-protocols. In press (2016)

Anna La Torre, Akina Hoshino, Christopher Cavanaugh, Carol B. Ware and Thomas A. Reh. The GIPC1-Akt1 pathway is required for the specification of the eye field in mouse embryonic stem cells. Stem Cells. May 26 (2015).

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. May 16 (2015). PMID: 25989023

Wilken M.S.; Brzezinski J.A.; La Torre A.; Siebenthall K.; Thurman R.; Sabo P.; Sandstrom R.S.; Vierstra J.; Canfield T.K.; Hansen R.S.; Bender M.A.; Stamatoyannopoulos J.; Reh T.A. DNase I hypersensitivity analysis of the mouse brain and retina identifies region-specific regulatory elements.
Epigenetics Chromatin. Feb 28 (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

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

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

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

Urena 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 Netrin1 signaling in neuronal migration and axonal guidance. Curr Biol. 14:840-50. 

Kondo H, Lavenex P, Amaral DG: (2008) Intrinsic connections of the macaque monkey hippocampal formation: I. Dentate Gyrus. Journal of Comparative Neurology. 511:497-520.

Bauman MD, Toscano JE, Babineau BA, Mason WA, Amaral DG: (2008) Emergence of

stereotypies in juvenile monkeys with neonatal amygdala or hippocampus lesions. Behavioral Neuroscience. 122:1005-1015.

Antoniadis EA, Winslow JT, Davis M, Amaral DG: (2008) The non human primate amygdala is necessary for the acquisition but not the retention of fear-potentiated startle: Effects of chronic amygdala lesions in the rhesus monkey. Biological Psychiatry. (in press)

Lavenex P, Lavenex PB, Amaral DG (2006) Spatial relational learning persists following neonatal hippocampal lesions in macaque monkeys. Nat Neurosci. 10:234-9.

Affiliations

Cell Biology and Human Anatomy