Department of Physiology and Membrane Biology, School of Medicine
Institute for Pediatric Regenerative Medicine
Mechanisms of nervous system and muscle development and regeneration
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.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Molecular, Cellular and Integrative Physiology
Specialties / Focus
- Cellular Physiology
- Developmental Physiology
- Molecular Physiology
- MCIP MCP210A Molecular and Cellular Physiology, Fall
- SOM HPH400 Human Physiology, Multiple
- Borodinsky lab - Institute for Pediatric Regenerative Medicine, Shriners Hospital
- Olesya Visina (Research Associate); Yesser Hadj Belgacem (Postdoctoral Fellow)
- Society for Neuroscience
- 1999 PhD Neuroscience University of Buenos Aires
Belgacem YH, Borodinsky LN. (2017) CREB at the crossroad of activity-dependent regulation of nervous system development and function. Book chapter, The Plastic Brain, Jaime Eugenin editor, Springer. Adv Exp Med Biol. 1015:19-39. doi: 10.1007/978-3-319-62817-2_2.
Balashova OA, Visina O, Borodinsky LN. (2017) Folate receptor alpha is necessary for neural plate cell apical constriction during Xenopus neural tube formation. Development, 144(8): 1518-1530. Featured in Science, April 7, 356 (6333): 39.
Belgacem YH, Hamilton AM, Shim S, Spencer KA, Borodinsky LN. (2016) The many hats of Sonic hedgehog signaling in nervous system development and disease. J. Dev. Biol., 4, 35; doi:10.3390/jdb4040035.
Tu MK, Levin JB, Hamilton AM, Borodinsky LN. (2016) Calcium signaling in skeletal muscle development, maintenance and regeneration. Cell Calcium, 59(2-3): 91-97.
Borodinsky LN, Belgacem YH. (2016) Crosstalk among electrical activity, trophic factors and morphogenetic proteins in the regulation of neurotransmitter phenotype specification. J Chem Neuroanat, 73:3-8.
Kamiguchi H and Borodinsky LN. (2015) Invited co-editors, Second messengers in neuronal development, Special Issue, Developmental Neurobiology, 75: 335-336.
Belgacem YH, Borodinsky LN. (2015) Inversion of Sonic hedgehog action on its canonical pathway by electrical activity. PNAS, 112: 4140-4145.
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.
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.
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.
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.
Swapna I, Borodinsky LN (2012). Interplay between electrical activity and BMP signaling regulates spinal neuron differentiation. PNAS, 109, 16336-16341.
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.
Belgacem YH, Borodinsky LN (2011) Sonic hedgehog signaling is decoded by calcium spike activity in the developing spinal cord. PNAS, 108: 4482-4487.
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.
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.
Spitzer NC, Borodinsky LN (2008) Implications of activity-dependent neurotransmitter-receptor matching. Philos. Trans. R. Soc. Lond B Biol Sci, 363: 1393-1399.
Borodinsky LN, Spitzer NC (2007) Activity-Dependent Neurotransmitter-Receptor Matching at the Neuromuscular Junction. PNAS, 104: 335-340.
Borodinsky LN, Spitzer NC (2006) Second messenger pas de deux: The coordinated dance between calcium and cAMP. Sci. STKE, 2006: pe22.
Spitzer NC, Borodinsky LN, Root CM (2005) Homeostatic activity-dependent paradigm for neurotransmitter specification. Cell Calcium, 37: 417-423.
Spitzer NC, Borodinsky LN, Root CM. (2005) Imaging calcium transients in developing Xenopus spinal neurons. In "Imaging in neuroscience and development: A laboratory manual". Yuste R and Konnerth A, Eds, Cold Spring Harbor Laboratory Press.
Spitzer NC, Root CM, Borodinsky LN (2004) Orchestrating neuronal differentiation: patterns of Ca2+ spikes specify transmitter choice. Trends Neurosci 27: 415-421.
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.
Borodinsky LN, OLeary 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.
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.
Borodinsky LN, Fiszman ML (2001) A single cell model to study changes in neuronal fractal dimension. Methods 24: 341-345.
Fiszman ML, Borodinsky LN, Neale JH (1999) GABA induces proliferation of immature cerebellar granule cells grown in vitro. Dev Brain Res 115: 1-8.
Borodinsky LN, Fiszman ML (1998) Extracellular potassium concentration regulates proliferation of immature cerebellar granule cells. Dev Brain Res 107: 43-48.
Borodinsky LN, Pesce G, Pomata PE, Fiszman ML (1997) Neurosteroid modulation of GABAA receptors in the developing rat brain cortex. Neurochem Int 31: 313-317.