The Drosophila sine oculis homeobox-containing gene is known to play an essential role in controlling the initial events of pattern formation in the eye disc and is also required for the development of other parts of the fly visual system including the optic lobes. In this paper, we report the isolation of a sequence-related gene referred to as Six3. Based on its amino acid sequence, this gene can be included in the new Six/sine oculis subclass of homeobox genes. Early on, Six3 expression is restricted to the anterior neural plate including areas that later will give rise to ectodermal and neural derivatives. Later, once the longitudinal axis of the brain bends, Six3 mRNA is also found in structures derived from the anterior neural plate: ectoderm of nasal cavity, olfactory placode and Rathke9s pouch, and also the ventral forebrain including the region of the optic recess, hypothalamus and optic vesicles. Based on this expression pattern, we conclude that Six3 is one of the most anterior homeobox gene reported to date. The high sequence similarity of Six3 with the Drosophila sine oculis, and its expression during eye development, suggests that this gene is the likely murine homologue. This finding supports the idea that mammals and insects share control genes such as eyeless/Pax6 (Halder, G., Callaerts, P. and Gehring, W. J. (1995) Science 267, 1788–1792), and also possibly other members of the regulatory cascade required for eye morphogenesis. In Small eye (Pax6) mouse mutants Six3 expression is not affected. Finally, based on the chromosomal localization and the expression pattern of the mouse Six3 gene, the human Six3 cognate could be a good candidate to be at least one of the genes affected in patients with holoprosencephaly type 2 due to an interstitial deletion of 2p21-p22. This region shares a homology with the distal region of mouse chromosome 17 where Six3 has been mapped.

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Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development

The pharyngeal muscles of Caenorhabditis elegans are single sarcomere muscles used for feeding. Like vertebrate cardiac and smooth muscles, C. elegans pharyngeal muscle does not express any of the known members of the MyoD family of myogenic factors. To identify mechanisms regulating gene expression in this tissue, we have characterized a pharyngeal muscle-specific enhancer from myo-2, a myosin heavy chain gene expressed exclusively in pharyngeal muscle. Assaying enhancer function in transgenic animals, we identified three subelements, designated A, B and C, that contribute to myo-2 enhancer activity. These subelements are individually inactive; however, any combination of two or more subelements forms a functional enhancer. The B and C subelements have distinct cell type specificities. A duplication of B activates transcription in a subset of pharyngeal muscles (m3, m4, m5 and m7). A duplication of C activates transcription in all pharyngeal cells, muscle and non-muscle. Thus, the activity of the myo-2 enhancer is regulated by a combination of pharyngeal muscle-type-specific and organ-specific signals. Screening a cDNA expression library, we identified a gene encoding an NK-2 class homeodomain protein, CEH-22, that specifically binds a site necessary for activity of the B subelement. CEH-22 protein is first expressed prior to myogenic differentiation and is present in the same subset of pharyngeal muscles in which B is active. Expression continues throughout embryonic and larval development. This expression pattern suggests CEH-22 plays a key role in pharyngeal muscle-specific activity of the myo-2 enhancer.

The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle

Gyrodactylid developmental biology: historical review, current status and future trends.

The porifera represent the most primitive phylum of the metazoa. We identified three homeobox-containing genes in the freshwater sponge (Ephydatia fluviatilis). Genomic DNA of the sponge was subjected to amplification by PCR with two primers that corresponded to the helix-1 and helix-3 regions of the homeodomain. Using the amplified products as probes, we isolated two homeobox genes, designated proxl and prox2. The amino acid sequences of the homeodomains of prox1 and prox2 were 72% and 62% identical to those of the NK-3 and Om(1 D) genes of Drosophila, respectively. Screening of a sponge genomic library with degenerate oligonucleotides that corresponded to helix 3 further revealed the presence of one more homeobox gene, prox3. The amino acid sequence of the homeodomain of the prox3 product was 77% identical to that of the msh gene product of human. These results indicate that, when the metazoa appeared during the course of evolution, the multiple and distinct classes of homeobox-containing genes that have been identified in higher organisms already existed.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1994.tb18732.x

Marcelo Vispo

Papers

Homeoboxes in flatworms.