Current research projects in our lab share a common goal of understanding the cellular and molecular mechanisms by which electrical activity, environmental factors and in general, changes in extrinsic and intrinsic cues influence nervous system development and regeneration. Different forms of activity are present at early stages of development, substantially before synapse formation, suggesting that neuronal activity participates in early steps of neuronal differentiation.
The hypotheses that we are testing in each of these projects attempt to challenge the idea that development occurs exclusively by a hardwired genetic program. Instead, we argue that tissue development progresses through a dynamic interplay between genetic programs and variable intrinsic and extrinsic cues.
We investigate the mechanisms by which two environmental factors, folic acid and antiepileptic drugs influence the incidence of neural tube defects. Our lab works with Xenopus laevis as a model system using a combination of methodologies including confocal microscopy, immunostaining, molecular biology, pharmacology, calcium imaging and electrophysiology.
Other projects in the lab are focused on spinal cord and muscle development and regeneration and the interplay between electrical activity and morphogenetic protein signaling.
2015 Belgacem YH, Borodinsky LN. Inversion of Sonic hedgehog action on its canonical pathway by electrical activity. PNAS, 2015 112: 4140-4145.
2015 Borodinsky, LN, Belgacem YH., Swapna I, Visina O, Balashova OA, Tu, MK, Sequerra EB, Levin JB, Spencer KA, Castro PA, Hamilton AM, Shim S. (2015) Regulation of neuronal development: Spatiotemporal integration of multiple developmental cues and second messengers. Invited review, Developmental Neurobiology, 75: 349-359.
2014 Dixit N, Wu D, Belgacem YH, Borodinsky LN, Gershwin M, Adamopoulos IE. (2014) Leukotriene B4 activates intracellular calcium and augments human osteoclastogenesis. Arthritis Research & Therapy, 16: 496.
2014 Tu MK, Borodinsky LN. (2014) Spontaneous calcium transients manifest in the regenerating muscle and are necessary for skeletal muscle replenishment. Cell Calcium, 56: 34-41.
2013 Spitzer NC, Borodinsky LN, Root CM. (2013) Imaging and manipulating calcium transients in developing Xenopus spinal neurons. Cold Spring Harbor Protocols. doi:10.1101/pdb.prot066803.
2012 Borodinsky LN, Belgacem YH, Swapna I, Sequerra EB. Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis. Neuropharmacology. (2012) Dec 25. pii: S0028-3908(12)00598-9. doi: 10.1016/j.neuropharm.2012.12.005. [Epub ahead of print].
2012 Swapna I, Borodinsky LN (2012). Interplay between electrical activity and BMP signaling regulates spinal neuron differentiation. PNAS, 109, 16336-16341.
2012 Borodinsky, LN, Belgacem YH, Swapna I (2012). Electrical activity as a developmental regulator in the formation of spinal cord circuits. Invited review. Current Opinion in Neurobiology, 22: 624-630.
2011 Belgacem YH, Borodinsky LN (2011) Sonic hedgehog signaling is decoded by calcium spike activity in the developing spinal cord. PNAS, 108: 4482-4487.
2011 Spitzer NC, Borodinsky LN, Root CM. (2011) Imaging calcium transients in developing Xenopus spinal neurons. In Imaging in Developmental Biology: A Laboratory Manual. Sharpe J, Rachel Wong and Yuste R, Eds, Cold Spring Harbor Laboratory Press.
2009 Borodinsky LN, Spitzer NC (2009) Mechanisms of Synapse Formation: Activity-Dependent Selection of Neurotransmitters and Receptors. In "Co-Existence and Co-Release of Classical Neurotransmitters. Ex uno plures". Gutierrez, Rafael, Ed., Springer.
2008 Spitzer NC, Borodinsky LN (2008) Implications of activity-dependent neurotransmitter-receptor matching. Philos. Trans. R. Soc. Lond B Biol Sci, 363: 1393-1399.
2007 Borodinsky LN, Spitzer NC (2007) Activity-Dependent Neurotransmitter-Receptor Matching at the Neuromuscular Junction. PNAS, 104: 335-340.
2006 Borodinsky LN, Spitzer NC (2006) Second messenger pas de deux: The coordinated dance between calcium and cAMP. Sci. STKE, 2006: pe22.
2005 Yuste R and Konnerth A, Eds, Cold Spring Harbor Laboratory Press. Spitzer NC, Borodinsky LN, Root CM (2005) Homeostatic activity-dependent paradigm for neurotransmitter specification. Cell Calcium, 37: 417-423.
2005 Spitzer NC, Borodinsky LN, Root CM. (2005) Imaging calcium transients in developing Xenopus spinal neurons. In "Imaging in neuroscience and development: A laboratory manual".
2004 Spitzer NC, Root CM, Borodinsky LN (2004) Orchestrating neuronal differentiation: patterns of Ca2+ spikes specify transmitter choice. Trends Neurosci 27: 415-421.
2004 Borodinsky LN, Root CM, Cronin J, Sann SB, Gu X, Spitzer NC. (2004) Activity-dependent homeostatic specification of transmitter expression in embryonic neurons. Nature 429: 523-530.
2003 Borodinsky LN, O’Leary D, Neale JH, Vicini S, Coso OA, Fiszman ML (2003) GABA-induced neurite outgrowth of cerebellar granule cells is mediated by GABAA receptor activation, calcium influx and CaMKII and MEK1 pathways. J Neurochem 84: 1411-1420.
2002 Borodinsky LN, Coso OA, Fiszman ML (2002) Contribution of Ca2+-calmodulin-dependent protein kinase II and mitogen-activated protein kinase kinase on neural activity-induced neurite outgrowth and survival of cerebellar granule cells. J Neurochem 80: 1062-1070.
2001 Borodinsky, L.N., Fiszman, M.L. ( 2001). A single cell model to study changes in neuronal fractal dimension. Methods 24:341-345.
1999 Fiszman, M.L., Borodinsky, L.N., Neale, J.H. (1999). GABA induces proliferation of immature cerebellar granular cells grown in vito. Dev Brain Res 115:1-8.
1999 Fiszman, M.L., Borodinsky, l.N., Sanz, O.P., Sica,R.E.P. (1999). Cu-Zn superoxide dismutase activity in red cells of patients with sporadic amyotrophic lateral sclerosis. J Neurol Sci 162:34:37.
1998 Borodinsky, l.N., Fiszman, M.L. (1998). Extracellular potassium concentration regulates proliferation of immature cerebellar granule cells. Dev Brain res 107:43-48.
1997 Borodinsky, L.N., Pesce G., Pomata, P.E., Fiszman, M.L. (1997). Neurosteroid modulation of GABAA receptors in the developing rat brain cortex. Neurochem Int 31:313-317.