The C. elegans Hox gene ceh-13 regulates cell migration and fusion in a non-colinear way. Implications for the early evolution of Hoxclusters

Abstract

BackgroundHox genes play a central role in axial patterning during animal development. They are clustered in the genome and specify cell fate in sequential domains along the anteroposterior (A-P) body axis in a conserved order that is co-linear with their relative genomic position. In the soil worm Caenorhabditis elegans, this striking rule of co-linearity is broken by the anterior Hox gene ceh-13, which is located between the two middle Hox paralogs, lin-39 and mab-5, within the loosely organized nematode Hox cluster. Despite its evolutionary and developmental significance, the functional consequence of this unusual genomic organization remains unresolved.ResultsIn this study we have investigated the role of ceh-13 in different developmental processes, and found that its expression and function are not restricted to the anterior body part. We show that ceh-13 affects cell migration and fusion as well as tissue patterning in the middle and posterior body regions too. These data reveal novel roles for ceh-13 in developmental processes known to be under the control of middle Hox paralogs. Consistently, enhanced activity of lin-39 and mab-5 can suppress developmental arrest and morphologic malformation in ceh-13 deficient animals.ConclusionOur findings presented here show that, unlike other Hox genes in C. elegans which display region-specific accumulation and function along the A-P axis, the expression and functional domain of the anterior Hox paralog ceh-13 extends beyond the anterior region of the worm. Furthermore, ceh-13 and the middle Hox paralogs share several developmental functions. Together, these results suggest the emergence of the middle-group Hox genes from a ceh-13-like primordial Hox ancestor.

Hox Proteins Act as Transcriptional Guarantors to Ensure Terminal Differentiation

“…The most anterior Hox gene ceh-13 was expressed in both ALM and PLM neurons, although the expression in PLM was much weaker (Figure 2A). This observation is consistent with previous findings that although ceh-13 is homologous to the Drosophila anterior Hox gene labial , its expression and function is found all along the A-P axis (Tihanyi et al, 2010). The fact that mutations in ceh-13 only affected the ALM differentiation but not PLM could result from the selective expression of the Hox cofactor ceh-20 in ALM but not PLM neurons (Figure 2B).…”

Hox Genes Promote Neuronal Subtype Diversification through Posterior Induction in Caenorhabditis elegans

“…Hox action in C. elegans and other nematodes has had to adapt to the loss of Hox genes, breaks in the Hox gene cluster, and imperfect colinearity (Aboobaker and Blaxter, 2010). Consequently, the most anterior Hox gene ceh-13/lab is expressed all along the A-P axis (Tihanyi et al, 2010), and its ubiquitous expression in both ALM and PLM neurons may be one of the reasons for adopting a posterior specification mechanism for PLM differentiation. Our results suggest that the anterior-specific expression of TALE cofactors ceh-20/Exd/Pbx and unc-62/hth/Meis may enable CEH-13 activity in the ALM neurons, but they inhibit EGL-5 activities in PLM neurons when misexpressed.…”

Spatial Regulation of lag-2 Transcription During Vulval Precursor Cell Fate Patterning in Caenorhabditis elegans lag-2

“…We also considered the potential involvement of members of Hox genes because lin-39 (Maloof and Kenyon 1998) and ceh-13 (Tihanyi et al 2010) are known to function in the VPCs. In particular, LIN-39 is present in all VPCs and prevents premature fusion of VPCs with the major hypodermal syncytium hyp7, so that the VPCs are competent to be induced by patterning signals (Clark et al 1993).…”