Homeobox Genes in Development
4D Microscopy
"Virtual Worm"-dbase
Home Page
Homeobox Genes in Evolution
Bioinformatics and Modelling
warthog & groundhog Genes
Homeobox Page

Homeobox genes

Homeobox genes are transcription factors that play key roles in development. The homeodomain is comprised of 3 alpha helices; the third helix binds to DNA in the major groove (See picture of the Antennapedia Homeodomain). Homeobox genes fall into many different classes, such as LIM, POU, Prd, Prd-like, CUT, Antennapedia, etc.
Over the years, we have been, and are working with a series of homeobox genes that fall into different classes.
For example: ceh-2 (Ems), ceh-8 (prd-like), ceh-14 (LIM), ceh-20 (PBC), ceh-21 (Onecut/cut), ceh-26 (Pros), ceh-32 (So), ceh-36 (Otd), ceh-37 (Otd), ceh-38 (Onecut/cut), ceh-43 (Dll), ceh-44 (Cux/cut). We are interested how these genes control developmental events, in particular during nervous system development.
Presently, we are studying the developmental role of the Otd homeobox genes ceh-36, ceh-37, and ttx-1 and their role in embryogenesis. One of the tools we use is 4D microscopy (see below), and we have observed early transient expression during embryogenesis for ceh-36 and ceh-37.

The LIM homeobox gene ceh-14 is another homeobox gene of particular interest to us. We are currently attempting to identify target genes of ceh-14 using gene chip technology and other methods and are planning to study its regulation during embryogenesis.

Expression of ceh-14::GFP in neurons of the head

ceh-14 gfp picture

In collaboration with Genome Canada, British Columbia (Dr. Baillie), we are also performing an expression survey of those homeobox genes that have not been studied in detail yet, to identify those, which may have an interesting role in nervous system development.

4D Microscopy

We have developed software to record not only 4D images during development, but we can also record live GFP expression patterns of genes during development. Thus, we can obtain rather precise information about the spaciotemperal expression pattern of developmentally important genes. We are applying this technology now to the analysis of homeobox gene expression patterns. Some of the software we have developed can be found on the Software Web page.  To see a GFP movie of a 4D recording, go the the main page.

and Modelling

A fundmental issue for Developmental Systems Biology is how the dynamic information that we obtain with our 4D recordings can be converted into a formalized, digitized form. Towards solving that problem, we are developing software to analyse the 4D microscopy data produced in order to convert this information into digital form that can be exported and exchanged. These data should build the basis for modelling of dynamic gene expression on a 4D model of C. elegans. Go to "Virtual Worm"-Base for more on this topic. We are also employing bioinformatics in order to compare functional conservation in evolution between worms and other model systems. Further, we plan to analyse promoter regions to integrate the information with Virtual Worm-Base to obtain better ideas of regulatory cascades of develomental processes.

Homeobox genes in evolution

homeodomainWe are interested in the evolution of homeobox genes to understand so as to correlate and correctly identify orthologs when comparing the functions of these genes across different animal phyla. We have and are still doing comprehensive analyses of homeobox genes in order to classify them. We maintain a Web page on Homeobox genes. As part of this ongoing work, we identified a novel domain in the C-terminus of HD-ZIP III homeobox genes with putative signalling function (Mukherjee K, Bürglin TR. (2006) Genome Analysis: MEKHLA, a novel domain with similarity to PAS domains, is fused to plant homeodomain-leucine zipper III proteins. Plant Physiol. 140(4):1142-1150).

warthog and groundhog genes

C. elegans contains a series of molecules with similarity to the Drosophila signaling molecule Hedgehog. However, the sequence conservation is restricted to the C-terminal domain, which has autoproteolytic activity. For a recent summary of the components of the Hedgehog signaling pathway in C. elegans see the Wormbook chapter "Homologs of the Hh signalling network in C. elegans".

Over 60 open reading frames directly or indirectly related to Hh are found in C. elegans. We have grouped these genes into several different families,
termed warthog, groundhog, ground-like, and more recently, quahog.
In a key paper we intially characterized these genes families:
Aspöck, G., Kagoshima, H., Niklaus, G., and Bürglin, T.R. (1999). Caenorhabditis elegans has scores of hedgehog-related genes: sequence and expression analysis. Genome Res., 9, 909-923.  Unfortunately, not all supplemental information for this paper is presented at "Genome Research"journal Web site, so here we provide all information:  Supplemental Information.

We are studying the function of these hh-related genes in C. elegans. We have found that the gene wrt-5 is essential during embryogenesis (Hao L, Aspöck G., Bürglin, TR. (2006) The hedgehog-related gene wrt-5 is essential for hypodermal development in Caenorhabditis elegans. Dev Biol. 290:323-336), and the gene qua-1 is essential for molting (Hao L, Mukherjee K, Liegeois S, Baillie D, Labouesse M, Bürglin TR. (2006) The hedgehog-related gene qua-1 is required for molting in Caenorhabditis elegans. Dev Dyn. 235:1469-1481).

Presently, we are conducting an expression survey for all genes in collaboration with Genome Canada, British Columbia.
Further, we are analysing the mutant phenotype of wrt-6.


We are involved in teach in several courses at Södertörns Högskola and Karolinska Institutet. One major course we teach is Bioinformatics, see the Bioinformatics Course Web site.