Genetic mechanisms and signaling pathways in the developing brain

Neurobiology

Cerebral cortex and the amygdala are the two most complex brain structures. The cortex is responsible for higher brain functions- perception, language, learning, memory; the amygdala is the "emotion center" of the brain. The broad interests of our group are in the genetic and epigenetic mechanisms that control the formation of these highly specialized structures. We use "knockout" and transgenic approaches, in-utero and tissue culture perturbation techniques, ChIP-seq and Mass spectrometry, neurocircuitry tracing and CLARITY-based approaches, and behavioral paradigms to pursue these questions.

 

Selected Publications

LHX2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11. Muralidharan B, Khatri Z, Maheshwari U, Gupta R, Roy B, Pradhan SJ, Karmodiya K, Padmanabhan H, Shetty AS, Balaji C, Kolthur-Seetharam U, Macklis JD, Galande S, Tole S. .J Neurosci. 2017 Jan 4;37(1):194-203. doi: 10.1523/JNEUROSCI.2836-16.2016. Read more ...

Dmrt5, a Novel Neurogenic Factor, Reciprocally Regulates Lhx2 to Control the Neuron-Glia Cell-Fate Switch in the Developing Hippocampus. Muralidharan B, Keruzore M, Pradhan SJ, Roy B, Shetty AS, Kinare V, D'Souza L, Maheshwari U, Karmodiya K, Suresh A, Galande S, Bellefroid EJ, Tole S. J Neurosci. 2017 Nov 15;37(46):11245-11254. doi: 10.1523/JNEUROSCI.1535-17.2017. Epub 2017 Oct 12. PMID: 29025924 .Read more ...

Novel functions of LHX2 and PAX6 in the developing telencephalon revealed upon combined loss of both genes. Godbole G, Roy A, Shetty AS, Tole S. Neural Dev. 2017 Nov 15;12(1):19. doi: 10.1186/s13064-017-0097-y.PMID:29141678 Read more ...

Bhavana M, Khatri Z, Maheshwari U, Gupta R, , Roy B, Pradhan S, Karmodiya K, Padmanabhan H, Shetty AS, Balaji CH, Kolthur U, Macklis JD, Galande S, and Tole S (2016).   Lhx2 interacts with the NURD complex and epigenetically modulates cortical neuron subtype regulators Fezf2 and Sox11 Journal of Neuroscience 2836-16.  PMID: 27909100 PDF Here..

Roy A, Gonzalez M, Pierani A, Meyer G,Tole S# (2014)  Lhx2 regulates the development of the forebrain hem system. Cerebral Cortex 24(5):1361-72 PDF Here..

Shetty AS,  Godbole G, Maheshawari U, Padmanabhan H, Chaudhary R, Muralidharan B, Hou P-S, Monuki ES, Kuo H-C, V Rema, Tole S# (2013) Lhx2 regulates a cortex-specific mechanism for barrel formation  PNAS doi:10.1073/pnas.1311158110 PDF Here..

Huilgol D, Udin, S, Shimogori T, Saha B, Roy A, Aizawa S., Hevner RF, Meyer G., Ohshima T, Pleasure SJ, Zhao Y, Tole S# (2013)Dual origins of the mammalian accessory olfactory bulb revealed by an evolutionarily conserved migratory stream Nature Neuroscience 16(2):157-65 PDF Here..

Subramanian L, Sarkar A, Ashwin S, Muralidharan B, Hari P, Piper M, Monuki ES, Bach I,Gronostajski R, Richards R, andTole, S# (2011)Transcription factor Lhx2is necessary and sufficient to suppress astrogliogenesis and promote neurogenesis in the developing hippocampus.
PNAS www.pnas.org/cgi/doi/10.1073/pnas.1101109108  PDF Here..

Mangale VS, Hirokawa KE, Satyaki PRV, GokulchandranN, ChikbireS, Subramanian L, Shetty AS, Martynoga B, Paul J, Mai MV, Li Y, Flanagan LA, Tole S#, and Monuki ES #  (2008)  Lhx2 selector activity specifies cortical identity  and suppresses hippocampal organizer fate  Science 319:304-309# co-corresponding authors  PDF Here..

Remedios, R., Huilgol, D., Saha, B., Hari, P., Bhatnagar, L., Kowalczyk T., Hevner R. F., Suda Y., Aizawa S.,  Ohshima, T., Stoykova, A., Tole, S#. (2007)  A novel stream of amygdaloid cells from the caudal telencephalon reveals a developmental link between the amygdala and the neocortex              
Nature Neuroscience  10 (9): 1141–1150 PDF Here..                     

Saha, B. Hari P., Huilgol, D. and Tole, S#.  (2007)  Dual role for LIM-HD gene Lhx2 in the formation of the lateral olfactory tract (LOT)  Journal of Neuroscience 27: 2290-2297  PDF Here..

Reviews

Huilgol D and Tole S# (2016) Cell migrations in the developing rodent olfactory system.
Cellular and Molecular Life Sciences 73(13), 2467-2490 PDF Here..

Subramanian L, and Tole S#.(2009)  Mechanisms underlying the specification, positional regulation and function of the cortical hem. Cerebral Cortex 19 (Suppl 1):i90-5. PDF Here..

Editorial:

Tole S. and Vale, R.  (2010).  Young leaders for Biology in India.  Science 329: 1441.  (Editorial)

Book Chapter:

Tole S. and Hebert J.  Telencephalon Patterning. “Cellular Migration and Formation of Neuronal Connections:  Comprehensive Developmental Neuroscience” (2013) John Rubenstein and PaskoRakic (Eds).  Academic Press.  ISBN: 978-0-12-397265-1