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NINDSNIMHNICHDNIDCDNEINIDCRNIANIAAANIDANHGRI NCCIHNIDDKNIEHSCCB

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Investigator

Timothy Petros, Ph.D.

Unit on Cellular and Molecular Neurodevelopment


Building 35 Room 3B-1002
35 Convent Drive
Bethesda MD 20892-3701
Office: (301) 496-3286
Lab: (301) 496-9986
Fax: (301) 496-9939
tim.petros@nih.gov

Dr. Petros received his B.S. from Brown University and his Ph.D. from Columbia University in 2008 working with Carol Mason, where he investigated the guidance factors that regulate retinal ganglion cell projections in the mouse visual system. From there Dr. Petros moved onto Stewart Anderson’s laboratory at Weill Cornell Medical College and utilized both in vitro stem cell techniques and in vivo electroporations to explore the mechanisms that regulate interneuron differentiation. He continued these pursuits in Gord Fishell’s laboratory at New York University where he began to untangle the intrinsic genetic programs and extrinsic environmental factors that direct interneuron diversity and maturation. He joined the NIH/NICHD as an investigator in 2017 where he plans to continue with these studies for the foreseeable future.



Inhibitory GABAergic interneurons are an extremely heterogeneous cell population that modulate and refine the flow of information throughout the nervous system. Our general understanding of the developmental mechanisms that generate this exquisite diversity remains largely unknown.  The goal of my lab is to dissect how intrinsic genetic programs combine with environment signals to sculpt interneuron diversity and maturation.

Numerous experiments indicate that initial fate decisions occur as interneuron progenitors become postmitotic during embryogenesis. However, when these young interneurons become locked into specific interneuron subtypes remains unknown. To test this idea, we are harvesting postnatal interneuron precursors in specific brain regions and transplanting them in new environments. This technique allows us to determine if transplanted interneurons adopt properties of the host environment (indicating a strong role for the environment in regulating interneuron diversity) or if they retain subtype features more consistent with the donor region.

The ability to longitudinally track gene expression within defined populations is essential for understanding how changes in expression mediate both development and plasticity. In an ideal scenario, we would like to identify actively transcribed genes in interneuron progenitors undergoing fate decisions while retaining the capacity to identify these cells mature subtype in the postnatal brain. To this end, we are developing a spatially and temporally inducible strategy that will allow us to label the transcriptome of interneuron progenitors. Labeled cells can be harvested at maturity when we have the tools to distinguish specific interneuron cell types, which will allow us to retrospectively look back in time to identify candidate fate determining genes expressed in specific interneuron populations. Our hope is that this strategy can be applied to investigate the temporal gene expression pattern of anyone’s favorite cell type.

Please visit our lab website for more information https://science.nichd.nih.gov/confluence/display/petros/Home

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  • 1) Tyson JA, Goldberg EM, Maroof AM, Xu Q, Petros TJ, Anderson SA (2015)
  • Duration of culture and Sonic Hedgehog signaling differentially specify PV versus SST cortical interneuron fates from embryonic stem cells
  • Development, 142, 1267-1278
  • 2) Miyoshi G, Young A, Petros T, Karayannis T, Chang MM, Lavado A, Iwano T, Nakajima M, Taniguchi H, Huang ZJ, Heintz N, Oliver G, Matsuzaki F, Machold RP, Fishell G (2015)
  • Prox1 regulates the subtype-specific development of caudal ganglionic eminence-derived GABAergic cortical interneurons
  • J. Neuro, 35(37), 12869-12889
  • 3) *Petros TJ, *Bultje R, Ross ME, Fishell G, Anderson SA (2015)
  • Apical versus basal neurogenesis directs cortical interneuron subclass fate
  • Cell Reports , 13(6), 1090-1095
  • 4) Petros TJ, Mauer C, Anderson SA (2013)
  • . Enhanced derivation of mouse ESC-derived cortical interneurons by expression of Nkx2.1
  • Stem Cell Res, 11(1), 647-656
  • 5) Kuwajima T, Yoshida Y, Takegahara N, Petros TJ, Kumanogoh A, Jessell TM, Sakurai T, Mason C (2012)
  • Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM promotes retinal axon midline crossing
  • Neuron, 74, 676-690
  • 6) *Petros TJ, *Bryson JB, Mason CA (2010)
  • Ephrin-B2 elicits differential growth cone collapse and axon retraction in retinal ganglion cells from distinct retinal regions
  • Dev. Neurobio, 70(11), 781-794
  • 7) Petros TJ, Shrestha BR, Mason C (2009)
  • Specificity and sufficiency of EphB1 in driving the ipsilateral retinal projection
  • J. Neurosci, 29(11), 3463-3474
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