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

 

*Kinare V, *Iyer A, Padmanabhan H, Godbole G, Khan T, Khatri Z, Maheshwari U, Bhavana M, Tole S. An evolutionarily conserved Lhx2-Ldb1 interaction regulates the acquisition of hippocampal cell fate and regional identity.  In press, Development

Godbole G, Shetty AS, Roy A, D’souza L, Chen B, Miyoshi G, Fishell G, ^#Tole S (2018) Hierarchical genetic interactions between FOXG1 and LHX2 regulate the formation of the cortical hem in the developing telencephalon.  Development 145 doi:10.1242/dev.154583

Bhavana M, Keruzore M, Roy B, Pradhan S, Shetty AS, Kinare V, D’Souza L, Maheshwari U, Karmodiya K, Suresh A, Galande S, ^#Bellefroid E, and ^#Tole S (2017b)  Dmrt5, a novel neurogenic factor, reciprocally regulates Lhx2 to control the neuron-glia cell fate switch in the developing hippocampus.   Journal of Neuroscience 37(46):11245

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 (2017a).   Lhx2 interacts with the NURD complex and epigenetically modulates cortical neuron subtype regulators Fezf2 and Sox11      Journal of Neuroscience 2836-16.  PMID: 27909100

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

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

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

Subramanian L, Sarkar A, Ashwin S, Muralidharan B, Hari P, Piper M, Monuki ES, Bach I,Gronostajski R, Richards R, and ^#Tole, 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

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 author

“Perspectives” based on this paper:  E. A. Grove “Organizing the Source of Memory” Science (319)  288-289

A highlight based on this paper:  M. H. Flight “Instructions for the Hippocampus”  Nature Reviews Neuroscience 9 (3): 164-165

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

“News and Views” based on this paper:  J. M. Deussing and W. Wurst “Amygdala and Neocortex:  Common Origins and Shared Mechanisms”   Nature Neuroscience 10 (9):  1081-1082

Reviews

Iyer A and Tole S. Neuronal diversity and reciprocal connectivity between the vertebrate hippocampus and septum. Wiley Interdiscip. Rev. Dev. Biol. doi: 10.1002/wdev.370

Chou S-J and Tole S.  Lhx2, an evolutionarily conserved, multifunctional regulator of forebrain development   Brain Research pii: S0006-8993(18)30116-1

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

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

Meeting Report: 

Tole S. and Shashidhara LS (2018) Gender-sensitization in Indian science: attitudes and action items” Tole and Shashidhara, 2018, in press, Current Science

Personal story: 

Nature Cell Biology’s  “Turning Points” series: Mentorship comes from many sources.

Tole, Nature Cell Biology 20:1010 (2018)

Blogs:  https://indiabioscience.org/authors/ShubhaTole

Taking the “ME” out of Mentorship

Scientist and Mommy  

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One possible plug for the leaky pipeline

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Advice for students starting out in research