Oliver Hobert, PhD
The main focus of the laboratory is to understand the molecular mechanisms that generate the astounding diversity of cell types in a nervous system. Using the C.elegans model system, we have revealed a core regulatory logic for how terminal neuronal identity is controlled in several different neuron types. We have demonstrated that these regulatory mechanisms are conserved in chordates. These insights have allowed us to reprogram the identity of heterologous cell types to that of specific neuron types. Venturing into a little explored area of neuronal diversification, we have developed a novel paradigm to study asymmetry across the left/right axis, by far the least understood axis in any nervous system, and identified a complex gene regulatory network that differentially controls terminal neuron identity across this axis.
Aside from our main focus on neuronal development, we have also studied the molecular machinery with which the nervous system responds to the environment (i) to modulate behavior and (ii) to ensure that it maintains its functional and structural integrity.
Employing new technologies that we developed, we continue to exploit the simplicity and experimental amenability of the worm to achieve a comprehensive understanding of the genetic programs that control the development of the C.elegans nervous system and we will continue to extend these insights to vertebrates.
“Genetic programs that control neural development in C. elegans"
- Kratsios, P, Pinan-Lucarré, B, Kerk, SY, Bessereau, JL and Hobert, O (2015) “Transcriptional coordination of synaptogenesis and neurotransmitter signaling”, Curr. Biol. 25, 1282–1295.
- Gordon, PM and Hobert, O (2015) “A competition mechanism for a homeotic neuron identity transformation in C. elegans”, Dev Cell in press.
- Howell, K, White, JG and Hobert O (2015) “Spatiotemporal control of a novel synaptic organizer molecule”, Nature in press (covered in News & Views).
- Vidal, B, Santella, A, Bao, Z, Chuang, CF and Hobert O (2015) “C. elegans SoxB genes are dispensable for embryonic neurogenesis but required for terminal differentiation of specific neuron types”, Development, in press.
- Rechavi, O, Houri-Ze'evi, L, Anava, S Goh WSG, Kerk, SY, Hannon, GJ, Hobert, O (2014) “Starvation-induced transgenerational inheritance of small RNAs in C.elegans”, Cell 158 , 277–287.
- Zhang, F, Bhattacharya, A, Nelson, JC, Abe, N, Gordon, P, Lloret-Fernandez, C, Maicas, M, Flames, N, Mann, RS, Colón-Ramos, DA and Hobert, O (2014) “The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types”, Development 141, 422-435.
- Cochella, L, Tursun, B, Hsieh, YW, Galindo, S, Johnston, RJ, Chuang, CF* and Hobert, O* (2014) “Two distinct types of neuronal asymmetries are controlled by the Caenorhabditis elegans zinc finger transcription factor die-1”, Genes Dev. 28, 34–43.
- Doitsidou, M, Flames, F, Topalidou, I, Abe, N, Felton, T, Remesal, L, Popovitchenko, T, Mann, RS, Chalfie, M and Hobert O (2013) ”A combinatorial regulatory signature controls terminal differentiation of the dopaminergic nervous system in C. elegans", Genes Dev. 27, 1391-1405.
- Serrano-Saiz, E, Poole, RJ, Felton, T, Zhang, F, De La Cruz, E and Hobert O (2013) “Modular control of glutamatergic neuronal identity in C. elegans by distinct homeodomain proteins", Cell 155, 659–673.
- Kratsios, P, Stolfi, A, Levine, M and Hobert, O (2012) "Coordinated regulation of cholinergic motor neuron traits through a conserved terminal selector gene", Nature Neurosci. 15, 205-214.
- Bénard, C, Blanchette, C, Recio, J and Hobert, O (2012) ”The secreted Ig domain proteins ZIG-5 and ZIG-8 cooperate with L1CAM/SAX-7 to maintain nervous system integrity in C. elegans “, PLoS Genetics 8(7): e1002819.
- Patel, T, Tursun, B, Rahe, D and Hobert, O (2012) " Removal of Polycomb Repressive Complex 2 makes C. elegans germ cells susceptible to direct conversion into specific somatic cell types", Cell Reports 2, 1178–1186.
- Cochella, L and Hobert, O (2012) “Embryonic priming of a miRNA locus predetermines postmitotic neuronal left-right asymmetry in C. elegans”, Cell 151, 1229–1242.
- Tursun, B, Patel, T, Kratsios, P and Hobert, O (2011) “Direct conversion of C. elegans germ cells into specific neuron types”, Science 331, 304-308.
- Poole, RJ, Bashllari, E, Cochella, L, Flower, EB and Hobert, O (2011) "A genome-wide RNAi screen for factors involved in neuronal specification in Caenorhabditis elegans", PLoS Genetics 7 (6), e1002109.
- Bertrand, V, Bisso, P, Poole RJ and Hobert, O (2011) "Notch-dependent induction of left/right asymmetry in C. elegans interneurons and motoneurons", Curr. Biol. 21, 1225-1231.
- Rechavi, O, Minevich, G and Hobert, O (2011) "Transgenerational inheritance of an acquired small RNA-based antiviral response in C.elegans ", Cell 147, 1248-1256 (recommended by Faculty of 1000).
- Pocock, R and Hobert, O (2010) "Hypoxia activates a latent circuit for processing gustatory information in C. elegans" Nature Neurosci. 13(5), 610-614.
- Flowers, E, Poole, R, Tursun, B, Bashllari, E, Pe'er, I and Hobert, O (2010) "UNC-37/Groucho interacts with a short Groucho-like protein, LSY-22, to control developmental decisions", Development 137, 1799-1805.
- Etchberger, JF , Flowers, EB, Poole, RJ, Bashllari, E and Hobert, O (2009) “Cis-regulatory mechanisms of left/right asymmetric neuron-subtype specification in C. elegans” Development 136:147-160.
- O'Meara, MM, Bigelow ,H, Flibotte, S, Etchberger, JF, Moerman, DG and Hobert, O (2009)“ Cis-regulatory mutations in the C.elegans homeobox gene locus cog-1 affect neuronal development” Genetics 181: 1679–1686.
- Bertrand, V and Hobert, O (2009) "Linking asymmetric cell division to the terminal differentiation program of postmitotic neurons in C. elegans" Dev. Cell 16, 563-575
- Flames, N and Hobert, O (2009) "Gene regulatory logic of dopaminergic neuron differentiation" Nature 458, 885-889.
- Ortiz, CO, Faumont, S, Takayama, J, Ahmed, HK, Goldsmith, AD, Pocock, R, McCormick KE, Kunimoto, H, Iino, Y, Lockery, S and Hobert, O (2009) “Lateralized gustatory behavior of C.elegans is controlled by specific receptor-type guanylyl cyclases”, Curr. Biol. 19, 996-1004.
- Sarin, S, Antonio, C, Tursun, B and Hobert, O (2009) “The C. elegans Tailless/TLX transcription factor nhr-67 controls neuronal identity and left/right asymmetric fate diversification” Development, 136(17):2933-44.
- Pocock, R and Hobert, O (2008) “Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans”, Nature Neurosci. 11, 894-900.
- Doitsidou, M, Flames, N, Lee, AC, Boyanov A and Hobert, O (2008) "Automated screening for mutants affecting dopaminergic neuron specification in C. elegans", Nature Methods 5 (10), 869-872.
- Bülow, H, Tjoe, N, Townley, RA, Didiano, D, van Kuppevelt, TH and Hobert, O (2008) " Extracellular sugar modifications provide instructive and cell-specific information for axon guidance choices", Curr. Biol. 18(24):1978-1985.
- Etchberger, JF, Lorch, A, Sleumer, MC, Zapf, R, Jones, SJ, Marra, MA, Holt, RA, Moerman DG and Hobert, O (2007) “The molecular signature and cis-regulatory architecture of a C. elegans gustatory neuron’ Genes Dev 21, 1653-1674.
- Ortiz, CO, Etchberger, JF, Posy, SL, Frøkjær-Jensen, C, Lockery, S, Honig B, and Hobert, O (2006) “Searching for neuronal left/right asymmetry: Genomewide analysis of nematode receptor-type guanylyl cyclases” , Genetics 173, 131-149.
- Benard, CY, Boyanov, A, Hall, DH and Hobert, O (2006) “DIG-1, a novel giant protein non-autonomously mediates maintenance of nervous system architecture”, Development 133, 3329-3340.
- Johnston, RJ, Copeland, JW, Fasnacht M, Etchberger, JF, Liu J, Honig B and Hobert, O (2006) “An unusual Zn finger/FH2 domain protein controls a left/right asymmetric neuronal fate decision in C.elegans”, Development 133, 3317-3328.
- Boulin, T, Pocock R and Hobert, O (2006) “ A novel Ephrin receptor-interacting Ig/FnIII domain protein provides C.elegans motoneurons with midline guidepost function”, Curr.Biol. 16, 1871-1883.
- Poole, R and Hobert, O (2006) “ Early embryonic programming of neuronal left/right asymmetry in C. elegans”, Curr. Biol. 16, 2279-92.
- Johnston, RJ, Chang, S, Etchberger, JF, Ortiz, CO and Hobert, O (2005) “MicroRNAs acting in a double-negative feedback loop to control a neuronal cell fate decision” Proc.Natl.Acad.Sci.USA, 102, 12449-12454.
- Johnston, RJ and Hobert, O (2005) “A novel C. elegans zinc finger transcription factor, lsy-2, required for the cell-type specific expression of the lsy-6 microRNA” Development 132, 5451-5460.
- Remy, JJ and Hobert O (2005) "An interneuronal chemoreceptor required for olfactory imprinting in C.elegans" Science 309, 787-790.
- Loria, PM, Hodgkin J and Hobert, O (2004) “A conserved postsynaptic transmembrane protein affecting neuromuscular signaling in C.elegans” J.Neurosci. 24(9), 2191-2201
- Wenick, AS and Hobert, O (2004) “Genomic cis-regulatory architecture and trans-acting regulators of a single interneuron-specific gene battery in C. elegans” Dev. Cell 6, 757-770.
- Chang, S, Johnston, RJ, Frkjr-Jensen, C, Lockery, S and Hobert, O (2004) "MicroRNAs act sequentially and asymetrically to control chemosensory laterality in the nematode" Nature 430, 785-789.
- Bülow, HE, Boulin, T and Hobert, O (2004) "Differential functions of the C. elegans FGF receptor in axon outgrowth and maintenance of axon position" Neuron 42, 367-374.
- Bülow, HE and Hobert, O (2004) "Differential sulfations and epimerization define heparan sulfate specificity in nervous system development" Neuron 41(5), 723-736.
- Tsalik, EL and Hobert, O (2003) "Functional mapping of neurons that control locomotory behavior in Caenorhabditis elegans” J.Neurobiol. 56, 178-197.
- Loria, PM, Duke, A, Rand, JB and Hobert, O (2003) "Two neuronal, nuclear-localized RNA-binding proteins involved in synaptic transmission” Curr.Biol. 13, 1317-1323.
- Chang, S, Johnston, RJ and Hobert, O (2003)" A transcriptional regulatory cascade that controls left/right asymmetry in chemosensory neurons of C. elegans” Genes Dev. 17, 2123-2137.
- Tsalik, EL, Niacaris, T, Wenick, AS, Pau, K, Avery L and Hobert, O (2003) "LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system” Dev.Biol. 263, 81-102.
- Johnston, RJ and Hobert, O (2003) "A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans" Nature 426, 845-849.
- Aurelio, O, Boulin, T. and Hobert, O (2003). Identification of spatialand temporal cues that regulate postembryonic expression of axonmaintenance factors in the C. elegans ventral nerve cord. Development130, 599-610.
- Aurelio, O, Hall, DH and Hobert, O (2002) "Immunoglobulin-domain proteins required for maintenance of ventral nerve cord organization"Science 295, 686-690.
- Bülow, H, Berry, K, Topper, L, Peles, E and Hobert, O (2002). Heparansulfate proteoglycan dependent induction of axon branching and axonmisrouting by the Kallmann syndrome gene kal-1. Proc.Natl.Acad.Sci USA99, 6346-6351.
- Hobert, O, Johnson, RJ and Chang, S (2002). Left/right asymmetry in thenervous system: The C. elegans paradigm. Nature Rev. Neurosci, 3(8),629-640.
- Altun-Gultekin, Z, Andachi, Y, Tsalik, E, Pilgrim, D, Kohara, Y andHobert, O (2001). A regulatory cascade of three homeobox genes, ceh-10,ttx-3 and ceh-23 controls cell fate specification of a definedinterneuron class in C.elegans. Development 128, 1951-1969.