Hobert O (2011) Curr Biol "Maintaining a memory by transcriptional autoregulation."

Hobert O

[Curr Biol, 2011]

One of the key features of cellular differentiation programs is stability. Although differentiation is reversible in principle, many components of the gene batteries induced upon terminal differentiation are maintained throughout a cell's life. For example, muscle cells continuously express the myosin gene, and GABAergic neurons continuously express genes for GABA synthesis and transport. Maintaining gene expression patterns in the nervous system is a particular challenge given the non-renewing nature and therefore extensive life span of many neuronal cell types.

Hobert O (2016) Curr Top Dev Biol "Terminal Selectors of Neuronal Identity."

Hobert O

[Curr Top Dev Biol, 2016]

The analysis of the developmental programs that define many different neuron types in the nematode Caenorhabditis elegans has revealed common themes in how distinct terminal differentiation programs are controlled. Rather than being controlled in a piece-meal manner, terminal identity features of a mature neuron are often coregulated by so-called terminal selector transcription factors. Here, I summarize the terminal selector concept and emphasize core features of this concept in the C. elegans system such as coregulation of terminal effector batteries, combinatorial control mechanisms, and the coupling of initiation and maintenance of neuronal identity.

Hobert O (2010) Genetics "The impact of whole genome sequencing on model system genetics: get ready for the ride."

Hobert O

[Genetics, 2010]

Much of our understanding of how organisms develop and function is derived from the extraordinarily powerful, classic approach of screening for mutant organisms in which a specific biological process is disrupted. Reaping the fruits of such forward genetic screens in metazoan model systems like Drosophila, Caenorhabditis elegans, or zebrafish traditionally involves time-consuming positional cloning strategies that result in the identification of the mutant locus. Whole genome sequencing (WGS) has begun to provide an effective alternative to this approach through direct pinpointing of the molecular lesion in a mutated strain isolated from a genetic screen. Apart from significantly altering the pace and costs of genetic analysis, WGS also provides new perspectives on solving genetic problems that are difficult to tackle with conventional approaches, such as identifying the molecular basis of multigenic and complex traits.

Hobert O et al. (1999) Trends Genet "Pax genes in Caenorhabditis elegans: a new twist."

Hobert O, Ruvkun GB

[Trends Genet, 1999]

The Pax genes encode transcription factors that control a wide variety of developmental events in taxa as diverse as vertebrates, arthopods and nematodes. These genes are characterized by the presence of a highly conserved DNA-binding domain, the Paired domain. Based on sequence similarities within the Paired domain, as well as the presence or absence of additional motifs (such as the homeodomain or octapeptide), PAX proteins can be subdivided into specific families.

Hobert O (2002) Biotechniques "PCR fusion-based approach to create reporter gene constructs for expression analysis in transgenic C. elegans."

Hobert O

[Biotechniques, 2002]

In the nematode Caenorhabditis elegans, gene expression patterns are most often determined by generating a fusion of the promoter gene under study to a reporter gene such as lacZ or gfp.

Hobert O et al. (1998) J Neurosci "Control of neural development and function in a thermoregulatory network by the LIM homeobox gene lin-11."

Liu Y, Ruvkun GB, Hobert O, D'Alberti T

[J Neurosci, 1998]

We show here that the lin-11 LIM homeobox gene is expressed in nine classes of head, ventral cord, and tail neurons and functions at a late step in the development of a subset of these neurons. In a lin-11 null mutant, all lin-11-expressing neurons are generated. Several of these neurons, however, exhibit neuroanatomical as well as functional defects. In the lateral head ganglion, lin-11 functions in a neural network that regulates thermosensory behavior. It is expressed in the AIZ interneuron that processes high temperature input and is required for the function of AIZ in the thermoregulatory neural network. Another LIM homeobox gene, ttx-3, functions in the antagonistic thermoregulatory interneuron AIY (). Thus, distinct LIM genes specify the functions of functionally related antagonistic interneurons within a neural network dedicated for thermoregulatory processes. Both ttx-3 and lin-11 expression are maintained throughout adulthood, suggesting that these LIM homeobox genes play a role in the functional maintenance of this neural circuit. We propose that particular LIM homeobox genes specify the distinct features of functionally related neurons that generate patterned behaviors.

Hobert O et al. (2002) Nat Rev Neurosci "Left-right asymmetry in the nervous system: the Caenorhabditis elegans model."

Hobert O, Johnston RJ, Chang S

[Nat Rev Neurosci, 2002]

Although the overall architecture of the nervous system of most animals shows a large degree of bilateral symmetry, there are striking patterns of left-right (L-R) asymmetry in the brains of some species. Some structures show L-R-specific differences in size, whereas others show asymmetrical patterns of gene expression and have diversified at the functional level. The nematode Caenorhabditis elegans offers a unique opportunity to address how symmetrical neuronal assemblies deviate to create functional lateralizations. Here, we provide a detailed cellular and molecular perspective on L-R asymmetry in the nervous system of C. elegans. We also give an overview of symmetry and asymmetry in the nervous systems of other organisms. We will relate these observations to general concepts of the mechanistic and phylogenetic origin of laterality.

Hobert O et al. (1997) Neuron "Regulation of interneuron function in the C. elegans thermoregulatory pathway by the ttx-3 LIM homeobox gene."

Ohshima YM, Mori I, Yamashita Y, Ruvkun GB, Liu Y, Hobert O, Honda H

[Neuron, 1997]

Neural pathways, which couple temperature-sensing neurons to motor and autonomic outputs, allow animals to navigate away from and adjust metabolism rates in response to the temperature extremes often encountered. ttx-3 is required for the specification of the AIY interneuron in the C. elegans neural pathway that mediates thermoregulation. ttx-3 null mutant animals exhibit the same thermotactic behavioral defect as that seen with laser ablation of AIY in wild type, suggesting that AIY does not signal in this mutant. ttx-3 encodes a LIM homeodomain protein. A ttx-3-GFP fusion gene is expressed specifically in the adult AIY interneuron pair, which connects to thermosensory neurons. In ttx-3 mutant animals, the AIY interneuron is generated but exhibits patterns of abnormal axonal outgrowth. Thus, the TTX-3 LIM homeodomain protein is likely to regulate the expression of target genes required late in AIY differentiation for the function of this interneuron in the thermoregulatory pathway. The ttx-3-dependent thermosensory pathway also couples to the temperature-modulated dauer neuroendocrine signaling pathway, showing that ttx-3 specifies AIY thermosensory information processing of both motor and autonomic outputs.

Hobert O et al. (1999) Development "The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons."

Ruvkun GB, Hobert O, Tessmar K

[Development, 1999]

We describe here the functional analysis of the C. elegans LIM homeobox gene lim-6, the ortholog of the mammalian Lmx-1a and b genes that regulate limb, CNS, kidney and eye development. lim-6 is expressed in a small number of sensory-, inter- and motorneurons, in epithelial cells of the uterus and in the excretory system. Loss of lim-6 function affects late events in the differentiation of two classes of GABAergic motorneurons which control rhythmic enteric muscle contraction. lim-6 is required to specify the correct axon morphology of these neurons and also regulates expression of glutamic acid decarboxylase, the rate limiting enzyme of GABA synthesis in these neurons. Moreover, lim-6 gene activity and GABA signaling regulate neuroendocrine outputs of the nervous system. In the chemosensory system lim-6 regulates the asymmetric expression of a probable chemosensory receptor. lim-6 is also required in epithelial cells for uterine morphogenesis. We compare the function of lim-6 to those of other LIM homeobox genes in C. elegans and suggest that LIM homeobox genes share the common theme of controlling terminal neural differentiation steps that when disrupted lead to specific neuroanatomical and neural function defects.

Hobert O et al. (1999) J Cell Biol "A conserved LIM protein that affects muscular adherens junction integrity and mechanosensory function in Caenorhabditis elegans."

Hobert O, Clark KA, Moerman DG, Ruvkun GB, Beckerle MC

[J Cell Biol, 1999]

We describe here the molecular and functional characterization of the Caenorhabditis elegans unc-97 gene, whose gene product constitutes a novel component of muscular adherens junctions. UNC-97 and homologues from several other species define the PINCH family, a family of LIM proteins whose modular composition of five LIM domains implicates them as potential adapter molecules. unc-97 expression is restricted to tissue types that attach to the hypodermis, specifically body wall muscles, vulval muscles, and mechanosensory neurons. In body wall muscles, the UNC-97 protein colocalizes with the beta-integrin PAT-3 to the focal adhesion-like attachment sites of muscles. Partial and complete loss-of-function studies demonstrate that UNC-97 affects the structural integrity of the integrin containing muscle adherens junctions and contributes to the mechanosensory functions of touch neurons. The expression of a Drosophila homologue of unc-97 in two integrin containing cell types, muscles, and muscle-attached epidermal cells, suggests that unc-97 function in adherens junction assembly and stability has been conserved across phylogeny. In addition to its localization to adherens junctions UNC-97 can also be detected in the nucleus, suggesting multiple functions for this LIM domain protein.