A C. elegans Hox gene switches on, off, on and off again to regulate proliferation, differentiation and morphogenesis

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1651-1661 ◽  
Author(s):  
S.J. Salser ◽  
C. Kenyon
Keyword(s):  
Cellular Response ◽  
Hox Genes ◽  
Sense Organ ◽  
Cellular Level ◽  
The Body ◽  
Body Region ◽  
Hox Gene ◽  
C Elegans ◽  
Independent Events ◽  
Gene Switches

Hox genes establish body pattern throughout the animal kingdom, but the role these genes play at the cellular level to modify and shape parts of the body remains a mystery. We find that the C. elegans Antennapedia homolog, mab-5, sequentially programs many independent events within individual cell lineages. In one body region, mab-5 first switches ON in a lineage to stimulate proliferation, then OFF to specify epidermal structures, then ON in just one branch of the lineage to promote neuroblast formation, and finally OFF to permit proper sense organ morphology. In a neighboring lineage, continuous mab-5 expression leads to a different pattern of development. Thus, this Hox gene achieves much of its power to diversify the anteroposterior axis through fine spatiotemporal differences in expression coupled with a changing pattern of cellular response.

A Wnt signaling pathway controls hox gene expression and neuroblast migration in C. elegans

Development ◽  
1999 ◽  
Vol 126 (1) ◽  
pp. 37-49 ◽  
Author(s):  
J.N. Maloof ◽  
J. Whangbo ◽  
J.M. Harris ◽  
G.D. Jongeward ◽  
C. Kenyon
Keyword(s):  
Gene Expression ◽  
Wnt Signaling ◽  
Wnt Pathway ◽  
Hox Genes ◽  
Wnt Signaling Pathway ◽  
Beta Catenin ◽  
Hox Gene ◽  
C Elegans ◽  
Neuroblast Migration ◽  
Pathway Gene

The specification of body pattern along the anteroposterior (A/P) body axis is achieved largely by the actions of conserved clusters of Hox genes. Limiting expression of these genes to localized regional domains and controlling the precise patterns of expression within those domains is critically important for normal patterning. Here we report that egl-20, a C. elegans gene required to activate expression of the Hox gene mab-5 in the migratory neuroblast QL, encodes a member of the Wnt family of secreted glycoproteins. We have found that a second Wnt pathway gene, bar-1, which encodes a beta-catenin/Armadillo-like protein, is also required for activation of mab-5 expression in QL. In addition, we describe the gene pry-1, which is required to limit expression of the Hox genes lin-39, mab-5 and egl-5 to their correct local domains. We find that egl-20, pry-1 and bar-1 all function in a linear genetic pathway with conserved Wnt signaling components, suggesting that a conserved Wnt pathway activates expression of mab-5 in the migratory neuroblast QL. Moreover, we find that members of this Wnt signaling system play a major role in both the general and fine-scale control of Hox gene expression in other cell types along the A/P axis.

The Pristionchus HOX gene Ppa-lin-39 inhibits programmed cell death to specify the vulva equivalence group and is not required during vulval induction

Development ◽  
1998 ◽  
Vol 125 (19) ◽  
pp. 3865-3873 ◽  
Author(s):  
R.J. Sommer ◽  
A. Eizinger ◽  
K.Z. Lee ◽  
B. Jungblut ◽  
A. Bubeck ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Nematode Species ◽  
Precursor Cells ◽  
Body Region ◽  
Ras Signaling ◽  
Equivalence Group ◽  
Hox Gene ◽  
C Elegans ◽  
Vulval Precursor Cells

In the two nematode species Caenorhabditis elegans and Pristionchus pacificus the vulva equivalence group in the central body region is specified by the Hox gene lin-39. C. elegans lin-39 mutants are vulvaless and the vulval precursor cells fuse with the surrounding hypodermis, whereas in P. pacificus lin-39 mutants the vulval precursor cells die by apoptosis. Mechanistically, LIN-39 might inhibit non-vulval fate (cell fusion in C. elegans, apoptosis in P. pacificus), promote vulval fate or do both. To study the mechanism of lin-39 function, we isolated P. pacificus cell death mutants and identified mutations in ced-3. Surprisingly, P. pacificus ced-3; lin-39 double mutants form a functional vulva in the absence of LIN-39 activity. Thus, in P. pacificus lin-39 specifies the vulva equivalence group by inhibiting programmed cell death. Furthermore, these data reveal an important difference in a later function of lin-39 between the two species. In C. elegans, LIN-39 specifies vulval cell fates in response to inductive RAS signaling, and in P. pacificus LIN-39 is not required for vulval induction. Thus, the comparative analysis indicates that lin-39 has distinct functions in both species although the gene is acting in a homologous developmental system.

The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling

Development ◽  
1998 ◽  
Vol 125 (2) ◽  
pp. 181-190 ◽  
Author(s):  
J.N. Maloof ◽  
C. Kenyon
Keyword(s):  
Body Region ◽  
Ras Signaling ◽  
Cell Fates ◽  
Vulval Development ◽  
Ras Pathway ◽  
Hox Gene ◽  
C Elegans ◽  
Cell Divisions ◽  
Ras Activation ◽  
Vulval Precursor Cells

The Ras signaling pathway specifies a variety of cell fates in many organisms. However, little is known about the genes that function downstream of the conserved signaling cassette, or what imparts the specificity necessary to cause Ras activation to trigger different responses in different tissues. In C. elegans, activation of the Ras pathway induces cells in the central body region to generate the vulva. Vulval induction takes place in the domain of the Hox gene lin-39. We have found that lin-39 is absolutely required for Ras signaling to induce vulval development. During vulval induction, the Ras pathway, together with basal lin-39 activity, up-regulates lin-39 expression in vulval precursor cells. We find that if lin-39 function is absent at this time, no vulval cell divisions occur. Furthermore, if lin-39 is replaced with the posterior Hox gene mab-5, then posterior structures are induced instead of a vulva. Our findings suggest that in addition to permitting vulval cell divisions to occur, lin-39 is also required to specify the outcome of Ras signaling by selectively activating vulva-specific genes.

egl-27 generates anteroposterior patterns of cell fusion in C. elegans by regulating Hox gene expression and Hox protein function

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3303-3312 ◽  
Author(s):  
Q. Ch'ng ◽  
C. Kenyon
Keyword(s):  
Gene Expression ◽  
Cell Fusion ◽  
Protein Function ◽  
Hox Genes ◽  
Positional Information ◽  
Cell Fates ◽  
Hox Proteins ◽  
Hox Gene ◽  
C Elegans ◽  
Hox Protein

Hox genes pattern the fates of the ventral ectodermal Pn.p cells that lie along the anteroposterior (A/P) body axis of C. elegans. In these cells, the Hox genes are expressed in sequential overlapping domains where they control the ability of each Pn.p cell to fuse with the surrounding syncytial epidermis. The activities of Hox proteins are sex-specific in this tissue, resulting in sex-specific patterns of cell fusion: in hermaphrodites, the mid-body cells remain unfused, whereas in males, alternating domains of syncytial and unfused cells develop. We have found that the gene egl-27, which encodes a C. elegans homologue of a chromatin regulatory factor, specifies these patterns by regulating both Hox gene expression and Hox protein function. In egl-27 mutants, the expression domains of Hox genes in these cells are shifted posteriorly, suggesting that egl-27 influences A/P positional information. In addition, egl-27 controls Hox protein function in the Pn.p cells in two ways: in hermaphrodites it inhibits MAB-5 activity, whereas in males it permits a combinatorial interaction between LIN-39 and MAB-5. Thus, by selectively modifying the activities of Hox proteins, egl-27 elaborates a simple Hox expression pattern into complex patterns of cell fates. Taken together, these results implicate egl-27 in the diversification of cell fates along the A/P axis and suggest that chromatin reorganization is necessary for controlling Hox gene expression and Hox protein function.

Homeobox genes and models for patterning the hindbrain and branchial arches

Development ◽  
1991 ◽  
Vol 113 (Supplement_1) ◽  
pp. 187-196 ◽  
Author(s):  
Paul Hunt ◽  
Jenny Whiting ◽  
Ian Muchamore ◽  
Heather Marshall ◽  
Robb Krumlauf
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Expression Pattern ◽  
Hox Genes ◽  
Homeobox Genes ◽  
Neural Plate ◽  
The Body ◽  
Hox Gene ◽  
Hox Code ◽  
Branchial Region

Antennapedia class homeobox genes, which in insects are involved in regional specification of the segmented central regions of the body, have been implicated in a similar role in the vertebrate hindbrain. The development of the hindbrain involves the establishment of compartments which are subsequently made distinct from each other by Hox gene expression, implying that the lineage of neural cells may be an important factor in their development. The hindbrain produces the neural crest that gives rise to the cartilages of the branchial skeleton. Lineage also seems to be important in the neural crest, as experiments have shown that the crest will form cartilages appropriate to its level of origin when grafted to a heterotopic location. We show how the Hox genes could also be involved in patterning the mesenchymal structures of the branchial skeleton. Recently it has been proposed that the rhombomererestricted expression pattern of Hox 2 genes is the result of a tight spatially localised induction from underlying head mesoderm, in which a prepattern of Hox expression is visible. We find no evidence for this model, our data being consistent with the idea that the spatially localised expression pattern is a result of segmentation processes whose final stages are intrinsic to the neural plate. We suggest the following model for patterning in the branchial region. At first a segment-restricted code of Hox gene expression becomes established in the neuroepithelium and adjacent presumptive neural crest. This expression is then maintained in the neural crest during migration, resulting in a Hox code in the cranial ganglia and branchial mesenchyme that reflects the crest's rhombomere of origin. The final stage is the establishment of Hox 2 expression in the surface ectoderm which is brought into contact with neural crest-derived branchial mesenchyme. The Hox code of the branchial ectoderm is established later in development than that of the neural plate and crest, and involves the same combination of genes as the underlying crest. Experimental observations suggest the idea of an instructive interaction between branchial crest and its overlying ectoderm, which would be consistent with our observations. The distribution of clusters of Antennapedia class genes within the animal kingdom suggests that the primitive chordates ancestral to vertebrates had at least one Hox cluster. The origin of the vertebrates is thought to have been intimately linked to the appearance of the neural crest, initially in the branchial region. Our data are consistent with the idea that the branchial region of the head arose in evolution before the more anterior parts, the development of the branchial region employing the Hox genes in a more determinate patterning system. In this scenario, the anterior parts of the head arose subsequently, which may explain the greater importance of interactions in their development, and the fact that Antennapedia class Hox genes are not expressed there.

Hox genes and the evolution of diverse body plans

1995 ◽  
Vol 349 (1329) ◽  
pp. 313-319 ◽  
Keyword(s):  
Transcription Factors ◽  
Hox Genes ◽  
Body Plan ◽  
The Body ◽  
Chromosomal Organization ◽  
Hox Gene ◽  
Body Regions ◽  
Taxonomic Groups ◽  
Novel Model ◽  
Sequence Characteristics

Homeobox genes encode transcription factors that carry out diverse roles during development. They are widely distributed among eukaryotes, but appear to have undergone an extensive radiation in the earliest metazoa, to generate a range of homeobox subclasses now shared between diverse metazoan phyla. The Hox genes comprise one of these subfamilies, defined as much by conserved chromosomal organization and expression as by sequence characteristics. These Hox genes act as markers of position along the antero—posterior axis of the body in nematodes, arthropods, chordates, and by implication, most other triploblastic phyla. In the arthropods this role is visualized most clearly in the control of segment identity. Exactly how Hox genes control the structure of segments is not yet understood, but their differential deployment between segments provides a model for the basis of segment diversity. Within the arthropods, distantly related taxonomic groups with very different body plans (insects, crustaceans) may share the same set of Hox genes. The expression of these Hox genes provides a new character to define the homology of different body regions. Comparisons of Hox gene deployment between insects and a branchiopod crustacean suggest a novel model for the derivation of the insect body plan.

scholarly journals REF-1, a protein with two bHLH domains, alters the pattern of cell fusion in C. elegans by regulating Hox protein activity

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1793-1804 ◽  
Author(s):  
S. Alper ◽  
C. Kenyon
Keyword(s):  
Cell Fate ◽  
Cell Fusion ◽  
Hox Genes ◽  
Body Axis ◽  
Body Region ◽  
Protein Activity ◽  
Cell Fate Decisions ◽  
C Elegans ◽  
Helix Loop Helix ◽  
Body Regions

Hox genes control the choice of cell fates along the anteroposterior (AP) body axis of many organisms. In C. elegans, two Hox genes, lin-39 and mab-5, control the cell fusion decision of the 12 ventrally located Pn.p cells. Specific Pn.p cells fuse with an epidermal syncytium, hyp7, in a sexually dimorphic pattern. In hermaphrodites, Pn.p cells in the mid-body region remain unfused whereas in males, Pn.p cells adopt an alternating pattern of syncytial and unfused fates. The complexity of these fusion patterns arises because the activities of these two Hox proteins are regulated in a sex-specific manner. MAB-5 activity is inhibited in hermaphrodite Pn.p cells and thus MAB-5 normally only affects the male Pn.p fusion pattern. Here we identify a gene, ref-1, that regulates the hermaphrodite Pn.p cell fusion pattern largely by regulating MAB-5 activity in these cells. Mutation of ref-1 also affects the fate of other epidermal cells in distinct AP body regions. ref-1 encodes a protein with two basic helix-loop-helix domains distantly related to those of the hairy/Enhancer of split family. ref-1, and another hairy homolog, lin-22, regulate similar cell fate decisions in different body regions along the C. elegans AP body axis.

scholarly journals From head to tail: a neuromechanical model of forward locomotion in Caenorhabditis   elegans

2018 ◽  
Vol 373 (1758) ◽  
pp. 20170374 ◽  
Author(s):  
Eduardo J. Izquierdo ◽  
Randall D. Beer
Keyword(s):  
Caenorhabditis Elegans ◽  
Biomechanical Model ◽  
Neural Model ◽  
Cellular Level ◽  
The Body ◽  
Rhythmic Pattern ◽  
Unknown Parameters ◽  
Forward Movement ◽  
C Elegans ◽  
Forward Locomotion

With 302 neurons and a near-complete reconstruction of the neural and muscle anatomy at the cellular level, Caenorhabditis elegans is an ideal candidate organism to study the neuromechanical basis of behaviour. Yet despite the breadth of knowledge about the neurobiology, anatomy and physics of C. elegans , there are still a number of unanswered questions about one of its most basic and fundamental behaviours: forward locomotion. How the rhythmic pattern is generated and propagated along the body is not yet well understood. We report on the development and analysis of a model of forward locomotion that integrates the neuroanatomy, neurophysiology and body mechanics of the worm. Our model is motivated by experimental analysis of the structure of the ventral cord circuitry and the effect of local body curvature on nearby motoneurons. We developed a neuroanatomically grounded model of the head motoneuron circuit and the ventral nerve cord circuit. We integrated the neural model with an existing biomechanical model of the worm's body, with updated musculature and stretch receptors. Unknown parameters were evolved using an evolutionary algorithm to match the speed of the worm on agar. We performed 100 evolutionary runs and consistently found electrophysiological configurations that reproduced realistic control of forward movement. The ensemble of successful solutions reproduced key experimental observations that they were not designed to fit, including the wavelength and frequency of the propagating wave. Analysis of the ensemble revealed that head motoneurons SMD and RMD are sufficient to drive dorsoventral undulations in the head and neck and that short-range posteriorly directed proprioceptive feedback is sufficient to propagate the wave along the rest of the body. This article is part of a discussion meeting issue ‘Connectome to behaviour: modelling C. elegans at cellular resolution’.

The expression of the C. elegans labial-like Hox gene ceh-13 during early embryogenesis relies on cell fate and on anteroposterior cell polarity

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4193-4200 ◽  
Author(s):  
C. Wittmann ◽  
O. Bossinger ◽  
B. Goldstein ◽  
M. Fleischmann ◽  
R. Kohler ◽  
...  
Keyword(s):  
Cell Fate ◽  
Cell Polarity ◽  
Hox Genes ◽  
Positional Information ◽  
Precursor Cell ◽  
Body Parts ◽  
Hox Gene ◽  
C Elegans ◽  
Fate Determinants ◽  
Cell Fate Determinants

Clusters of homeobox-containing HOM-C/hox genes determine the morphology of animal body plans and body parts and are thought to mediate positional information. Here, we describe the onset of embryonic expression of ceh-13, the Caenorhabditis elegans orthologue of the Drosophila labial gene, which is the earliest gene of the C. elegans Hox gene cluster to be activated in C. elegans development. At the beginning of gastrulation, ceh-13 is asymmetrically expressed in posterior daughters of anteroposterior divisions, first in the posterior daughter of the intestinal precursor cell E and then in all posterior daughters of the AB descendants ABxxx. In this paper, we present evidence that supports position-independent activation of ceh-13 during early C. elegans embryogenesis, which integrates cell fate determinants and cell polarity cues. Our findings imply that mechanisms other than cell-extrinsic anteroposterior positional signals play an important role in the activation and regulation of the C. elegans Hox gene ceh-13.

Crustacean (malacostracan) Hox genes and the evolution of the arthropod trunk

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2239-2249 ◽  
Author(s):  
A. Abzhanov ◽  
T.C. Kaufman
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
The Body ◽  
Ancestral State ◽  
Porcellio Scaber ◽  
Hox Gene ◽  
Overlapping Domains ◽  
Discrete Domains

Representatives of the Insecta and the Malacostraca (higher crustaceans) have highly derived body plans subdivided into several tagma, groups of segments united by a common function and/or morphology. The tagmatization of segments in the trunk, the part of the body between head and telson, in both lineages is thought to have evolved independently from ancestors with a distinct head but a homonomous, undifferentiated trunk. In the branchiopod crustacean, Artemia franciscana, the trunk Hox genes are expressed in broad overlapping domains suggesting a conserved ancestral state (Averof, M. and Akam, M. (1995) Nature 376, 420–423). In comparison, in insects, the Antennapedia-class genes of the homeotic clusters are more regionally deployed into distinct domains where they serve to control the morphology of the different trunk segments. Thus an originally Artemia-like pattern of homeotic gene expression has apparently been modified in the insect lineage associated with and perhaps facilitating the observed pattern of tagmatization. Since insects are the only arthropods with a derived trunk tagmosis tested to date, we examined the expression patterns of the Hox genes Antp, Ubx and abd-A in the malacostracan crustacean Porcellio scaber (Oniscidae, Isopoda). We found that, unlike the pattern seen in Artemia, these genes are expressed in well-defined discrete domains coinciding with tagmatic boundaries which are distinct from those of the insects. Our observations suggest that, during the independent tagmatization in insects and malacostracan crustaceans, the homologous ‘trunk’ genes evolved to perform different developmental functions. We also propose that, in each lineage, the changes in Hox gene expression pattern may have been important in trunk tagmatization.

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