Genetic Analysis of the development of neural circuits in C. elegans
The focus of the lab is the study of the molecular mechanisms that lead to the generation of specific neural circuits in the brain, which in turn subserve specific behaviors. We are interested in the developmental aspect of neural circuit generation as well as later aspects of maintenance and modification of neural circuits, which presumably are the basis of learning and memory processes. Due to the complexity of the vertebrate brain, we use the much simpler nervous system of the nematode C. elegans as a model system. We know the complete connectivity of every single neuron in C. elegans.
We have used single cell laser ablations to identify specific neural circuits required to execute specific behaviors. The completely sequenced genome of C. elegans as well as its amenability to classical genetic methods allow the identification of molecules that are required for the neural differentiation and the generation of specific neural circuits. Currently we are interested in a specific class of transcription factors, the LIM homeobox genes. Seven of these genes exist in C. elegans and we have characterized four of these so far. All these genes are expressed in a restricted subset of postmitotic neurons in the brain; their expression maintained throughout adulthood suggests a role for these genes not only in the initial differentation process but also in the maintenance of the differentiated state. Indeed, our molecular, genetic, and behavioral analysis of several of these genes demonstrates their involvement in late neural differentiation processes. Two of these genes, ttx-3 and lin-11 are required to specify the function of two interneurons in a neural circuit that subserves a learning and memory paradigm in C. elegans, the thermosensory neural circuit. Another gene, lim-6 is required for the rhythmic execution of a motor program and is presumably also involved in sensory neural processes. Each of these genes has vertebrate homologues and we believe that understanding how these genes act in C. elegans will be directly applicable to neural circuit control in vertebrates. We use genetic and biochemical approaches to identify novel genes that act together or downstream of these genes to determine and specify neural circuits in C. elegans.
Oliver Hobert obtained his diploma in biochemistry at the University of Bayreuth, Germany, in 1992 and his Ph.D. in molecular biology at the Max Planck Institute for Biochemistry in Munich in 1995. Fascinated by the experimental amenability of the model system Caenorhabditis elegans, Hobert joined Gary Ruvkun's lab at Harvard Medical School for postdoctoral research. Studies on the function of several transcription factors allowed him to define his long-term research interest in how neurons in the nervous system are genetically programmed during development.
In 1999, Hobert took a faculty position in the Department of Biochemistry and Molecular Biophysics at Columbia University College of Physicians and Surgeons, where he continued to pursue and expand his research interest in nervous system development.
| 1992 |
Diploma in biochemistry, University of Bayreuth, Germany |
| 1995 |
Ph.D. in molecular biology, Max Planck Institute for Biochemistry, Munich |
McKnight Endowment for the Neurosciences Award
Human Frontier Science Program 10th Anniversary Award
- Remy, JJ and Hobert O (2005) "An interneuronal chemoreceptor required for olfactory imprinting in C.elegans" Science 309, 787-790
- Chang, S, Johnston, RJ, Frøkjær-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
- Buuml;low, HE and Hobert, O (2004) "Differential sulfations and epimerization define heparan sulfate specificity in nervous system development" Neuron 41(5), 723-736
- Johnston, RJ and Hobert, O (2003) "A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans" Nature 426, 845-849
- Aurelio, O, Hall, DH and Hobert, O (2002) "Immunoglobulin-domain proteins required for maintenance of ventral nerve cord organization"Science 295, 686-690
|
 |
|
