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Neurons refine the Caenorhabditis elegans body plan by directing axial patterning by Wnts.

Modzelewska K, Lauritzen A, Hasenoeder S, Brown L, Georgiou J, Moghal N - PLoS Biol. (2013)

Bottom Line: Surprisingly, despite high levels of Ror expression in many other cells, these cells cannot substitute for the CAN axons in patterning the epidermis, nor can cells expressing a secreted Wnt inhibitor, SFRP-1.Thus, unmyelinated axon tracts are critical for patterning the C. elegans body.Our findings suggest that the evolution of neurons not only improved metazoans by increasing behavioral complexity, but also by expanding the diversity of developmental patterns generated by growth factors such as Wnts.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.

ABSTRACT
Metazoans display remarkable conservation of gene families, including growth factors, yet somehow these genes are used in different ways to generate tremendous morphological diversity. While variations in the magnitude and spatio-temporal aspects of signaling by a growth factor can generate different body patterns, how these signaling variations are organized and coordinated during development is unclear. Basic body plans are organized by the end of gastrulation and are refined as limbs, organs, and nervous systems co-develop. Despite their proximity to developing tissues, neurons are primarily thought to act after development, on behavior. Here, we show that in Caenorhabditis elegans, the axonal projections of neurons regulate tissue progenitor responses to Wnts so that certain organs develop with the correct morphology at the right axial positions. We find that foreshortening of the posteriorly directed axons of the two canal-associated neurons (CANs) disrupts mid-body vulval morphology, and produces ectopic vulval tissue in the posterior epidermis, in a Wnt-dependent manner. We also provide evidence that suggests that the posterior CAN axons modulate the location and strength of Wnt signaling along the anterior-posterior axis by employing a Ror family Wnt receptor to bind posteriorly derived Wnts, and hence, refine their distributions. Surprisingly, despite high levels of Ror expression in many other cells, these cells cannot substitute for the CAN axons in patterning the epidermis, nor can cells expressing a secreted Wnt inhibitor, SFRP-1. Thus, unmyelinated axon tracts are critical for patterning the C. elegans body. Our findings suggest that the evolution of neurons not only improved metazoans by increasing behavioral complexity, but also by expanding the diversity of developmental patterns generated by growth factors such as Wnts.

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vab-8 mutations that affect neuronal cell body positioning and axon outgrowth cause epidermal patterning defects.(A) vab-8 mutations cause P8.p to adopt a vulval fate. In wild-type animals, P8.p divides once, but never forms vulval tissue. (B) vab-8 mutations increase the frequency of P3.p becoming a vulval progenitor. 50% of the time, P3.p receives sufficient Wnt signaling to become a vulval progenitor and divides once. (C) Upper panel depicts wild-type signaling by Wnts and EGF that promotes vulval development with mirror image symmetry. MOM-2 and LIN-44 Wnts dominate over EGL-20/Wnt to polarize P7.p towards the anterior. Lower panel shows a wild-type 22-cell vulva with normal symmetry at the mid-L4 stage. (D) Upper panel depicts abnormal Wnt signaling in vab-8 mutants that causes the formation of vulval tissue with a P-Rvl phenotype. EGL-20/Wnt dominates over MOM-2 and LIN-44 Wnts, preventing P7.p from reorienting towards the anterior. Lower panel shows a P-Rvl vulva at the mid-L4 stage. In (C) and (D), EGL-20/Wnt was overexpressed from its native promoter with the muIs49 transgene. Scale bar is 10 µm. Colors depict Wnt signaling as in Figure 1. p-Values were calculated using a two-tailed Fisher's exact test versus wild-type animals (A and B) or as otherwise indicated (A and D).
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pbio-1001465-g002: vab-8 mutations that affect neuronal cell body positioning and axon outgrowth cause epidermal patterning defects.(A) vab-8 mutations cause P8.p to adopt a vulval fate. In wild-type animals, P8.p divides once, but never forms vulval tissue. (B) vab-8 mutations increase the frequency of P3.p becoming a vulval progenitor. 50% of the time, P3.p receives sufficient Wnt signaling to become a vulval progenitor and divides once. (C) Upper panel depicts wild-type signaling by Wnts and EGF that promotes vulval development with mirror image symmetry. MOM-2 and LIN-44 Wnts dominate over EGL-20/Wnt to polarize P7.p towards the anterior. Lower panel shows a wild-type 22-cell vulva with normal symmetry at the mid-L4 stage. (D) Upper panel depicts abnormal Wnt signaling in vab-8 mutants that causes the formation of vulval tissue with a P-Rvl phenotype. EGL-20/Wnt dominates over MOM-2 and LIN-44 Wnts, preventing P7.p from reorienting towards the anterior. Lower panel shows a P-Rvl vulva at the mid-L4 stage. In (C) and (D), EGL-20/Wnt was overexpressed from its native promoter with the muIs49 transgene. Scale bar is 10 µm. Colors depict Wnt signaling as in Figure 1. p-Values were calculated using a two-tailed Fisher's exact test versus wild-type animals (A and B) or as otherwise indicated (A and D).

Mentions: vab-8 encodes a long isoform, VAB-8L, and several short isoforms collectively called VAB-8S [31]. These proteins act in a few neurons to promote their posterior-directed migration and axon outgrowth [31],[32]. Both isoforms possess C-terminal coiled-coil domains, with VAB-8L having an additional N-terminal kinesin domain. In wild-type animals, only the three central vulval progenitors (P5.p–P7.p) adopt vulval fates. However, in vab-8(gm99) and vab-8(gm138) mutants, which lack both isoforms and have anteriorly displaced neurons, the posterior P8.p progenitor also acquired a vulval fate (Figure 2A). In the anterior epidermis of wild-type animals, Wnt signaling is limiting in P3.p because of its distance from the posterior Wnts; therefore, it becomes a progenitor only 50% of the time (Figure 1B and 2B). vab-8 mutations did not cause ectopic vulval fates in anterior P3.p or P4.p (n = 170), but they increased the frequency with which P3.p became a vulval progenitor (Figure 2B). In the mid-body, at low frequency, vab-8 mutations disrupted the mirror image symmetry of the vulva. Initially, during the generation of the vulval progenitors in wild-type animals, posterior-derived EGL-20/Wnt causes P5.p and P7.p to polarize and face towards the posterior (Figure 1B) [16]. Later, centrally produced MOM-2 and LIN-44 Wnts maintain P5.p polarity towards the posterior, but cause P7.p to reorient and face towards the anterior (Figures 1C and 2C) [16],[17]. vab-8 mutations caused a “posterior-reversed vulval lineage” (P-Rvl) phenotype, in which P7.p remained polarized towards the posterior EGL-20/Wnt signal, so that its subsequent cell divisions caused a second vulval invagination (Figure 2D).


Neurons refine the Caenorhabditis elegans body plan by directing axial patterning by Wnts.

Modzelewska K, Lauritzen A, Hasenoeder S, Brown L, Georgiou J, Moghal N - PLoS Biol. (2013)

vab-8 mutations that affect neuronal cell body positioning and axon outgrowth cause epidermal patterning defects.(A) vab-8 mutations cause P8.p to adopt a vulval fate. In wild-type animals, P8.p divides once, but never forms vulval tissue. (B) vab-8 mutations increase the frequency of P3.p becoming a vulval progenitor. 50% of the time, P3.p receives sufficient Wnt signaling to become a vulval progenitor and divides once. (C) Upper panel depicts wild-type signaling by Wnts and EGF that promotes vulval development with mirror image symmetry. MOM-2 and LIN-44 Wnts dominate over EGL-20/Wnt to polarize P7.p towards the anterior. Lower panel shows a wild-type 22-cell vulva with normal symmetry at the mid-L4 stage. (D) Upper panel depicts abnormal Wnt signaling in vab-8 mutants that causes the formation of vulval tissue with a P-Rvl phenotype. EGL-20/Wnt dominates over MOM-2 and LIN-44 Wnts, preventing P7.p from reorienting towards the anterior. Lower panel shows a P-Rvl vulva at the mid-L4 stage. In (C) and (D), EGL-20/Wnt was overexpressed from its native promoter with the muIs49 transgene. Scale bar is 10 µm. Colors depict Wnt signaling as in Figure 1. p-Values were calculated using a two-tailed Fisher's exact test versus wild-type animals (A and B) or as otherwise indicated (A and D).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3539944&req=5

pbio-1001465-g002: vab-8 mutations that affect neuronal cell body positioning and axon outgrowth cause epidermal patterning defects.(A) vab-8 mutations cause P8.p to adopt a vulval fate. In wild-type animals, P8.p divides once, but never forms vulval tissue. (B) vab-8 mutations increase the frequency of P3.p becoming a vulval progenitor. 50% of the time, P3.p receives sufficient Wnt signaling to become a vulval progenitor and divides once. (C) Upper panel depicts wild-type signaling by Wnts and EGF that promotes vulval development with mirror image symmetry. MOM-2 and LIN-44 Wnts dominate over EGL-20/Wnt to polarize P7.p towards the anterior. Lower panel shows a wild-type 22-cell vulva with normal symmetry at the mid-L4 stage. (D) Upper panel depicts abnormal Wnt signaling in vab-8 mutants that causes the formation of vulval tissue with a P-Rvl phenotype. EGL-20/Wnt dominates over MOM-2 and LIN-44 Wnts, preventing P7.p from reorienting towards the anterior. Lower panel shows a P-Rvl vulva at the mid-L4 stage. In (C) and (D), EGL-20/Wnt was overexpressed from its native promoter with the muIs49 transgene. Scale bar is 10 µm. Colors depict Wnt signaling as in Figure 1. p-Values were calculated using a two-tailed Fisher's exact test versus wild-type animals (A and B) or as otherwise indicated (A and D).
Mentions: vab-8 encodes a long isoform, VAB-8L, and several short isoforms collectively called VAB-8S [31]. These proteins act in a few neurons to promote their posterior-directed migration and axon outgrowth [31],[32]. Both isoforms possess C-terminal coiled-coil domains, with VAB-8L having an additional N-terminal kinesin domain. In wild-type animals, only the three central vulval progenitors (P5.p–P7.p) adopt vulval fates. However, in vab-8(gm99) and vab-8(gm138) mutants, which lack both isoforms and have anteriorly displaced neurons, the posterior P8.p progenitor also acquired a vulval fate (Figure 2A). In the anterior epidermis of wild-type animals, Wnt signaling is limiting in P3.p because of its distance from the posterior Wnts; therefore, it becomes a progenitor only 50% of the time (Figure 1B and 2B). vab-8 mutations did not cause ectopic vulval fates in anterior P3.p or P4.p (n = 170), but they increased the frequency with which P3.p became a vulval progenitor (Figure 2B). In the mid-body, at low frequency, vab-8 mutations disrupted the mirror image symmetry of the vulva. Initially, during the generation of the vulval progenitors in wild-type animals, posterior-derived EGL-20/Wnt causes P5.p and P7.p to polarize and face towards the posterior (Figure 1B) [16]. Later, centrally produced MOM-2 and LIN-44 Wnts maintain P5.p polarity towards the posterior, but cause P7.p to reorient and face towards the anterior (Figures 1C and 2C) [16],[17]. vab-8 mutations caused a “posterior-reversed vulval lineage” (P-Rvl) phenotype, in which P7.p remained polarized towards the posterior EGL-20/Wnt signal, so that its subsequent cell divisions caused a second vulval invagination (Figure 2D).

Bottom Line: Surprisingly, despite high levels of Ror expression in many other cells, these cells cannot substitute for the CAN axons in patterning the epidermis, nor can cells expressing a secreted Wnt inhibitor, SFRP-1.Thus, unmyelinated axon tracts are critical for patterning the C. elegans body.Our findings suggest that the evolution of neurons not only improved metazoans by increasing behavioral complexity, but also by expanding the diversity of developmental patterns generated by growth factors such as Wnts.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.

ABSTRACT
Metazoans display remarkable conservation of gene families, including growth factors, yet somehow these genes are used in different ways to generate tremendous morphological diversity. While variations in the magnitude and spatio-temporal aspects of signaling by a growth factor can generate different body patterns, how these signaling variations are organized and coordinated during development is unclear. Basic body plans are organized by the end of gastrulation and are refined as limbs, organs, and nervous systems co-develop. Despite their proximity to developing tissues, neurons are primarily thought to act after development, on behavior. Here, we show that in Caenorhabditis elegans, the axonal projections of neurons regulate tissue progenitor responses to Wnts so that certain organs develop with the correct morphology at the right axial positions. We find that foreshortening of the posteriorly directed axons of the two canal-associated neurons (CANs) disrupts mid-body vulval morphology, and produces ectopic vulval tissue in the posterior epidermis, in a Wnt-dependent manner. We also provide evidence that suggests that the posterior CAN axons modulate the location and strength of Wnt signaling along the anterior-posterior axis by employing a Ror family Wnt receptor to bind posteriorly derived Wnts, and hence, refine their distributions. Surprisingly, despite high levels of Ror expression in many other cells, these cells cannot substitute for the CAN axons in patterning the epidermis, nor can cells expressing a secreted Wnt inhibitor, SFRP-1. Thus, unmyelinated axon tracts are critical for patterning the C. elegans body. Our findings suggest that the evolution of neurons not only improved metazoans by increasing behavioral complexity, but also by expanding the diversity of developmental patterns generated by growth factors such as Wnts.

Show MeSH
Related in: MedlinePlus