Genes in Development
|Homeobox Genes in Evolution
||Bioinformatics and Modelling
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
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.
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.
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.
Over 60 open reading frames directly or indirectly related to Hh are
found in C. elegans. We have grouped these genes into several different
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.