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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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Related in: MedlinePlus

Model for neuronal control of axial patterning by Wnts.(A) In wild-type animals, EGL-20/Wnt (orange) (and possibly CWN-1/Wnt [green]) is sequestered by the Ror/CAM-expressing posterior CAN axons. At the end of the L2 larval stage, this sequestration allows MOM-2 and LIN-44 Wnts (blue) to reorient and polarize P7.p towards the anterior (horizontal arrows). During the L3 larval stage, anterior-facing P7.p divides with the mirror image pattern of P5.p, and P8.p does not receive sufficient Wnt or EGF signaling to adopt a vulval fate. (B) If the posterior CAN axons do not extend far enough into the posterior body, where EGL-20/Wnt is produced, an abnormally high concentration of EGL-20 occurs, which prevents anterior polarization of P7.p, and causes ectopic vulval tissue to form at P8.p.
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pbio-1001465-g009: Model for neuronal control of axial patterning by Wnts.(A) In wild-type animals, EGL-20/Wnt (orange) (and possibly CWN-1/Wnt [green]) is sequestered by the Ror/CAM-expressing posterior CAN axons. At the end of the L2 larval stage, this sequestration allows MOM-2 and LIN-44 Wnts (blue) to reorient and polarize P7.p towards the anterior (horizontal arrows). During the L3 larval stage, anterior-facing P7.p divides with the mirror image pattern of P5.p, and P8.p does not receive sufficient Wnt or EGF signaling to adopt a vulval fate. (B) If the posterior CAN axons do not extend far enough into the posterior body, where EGL-20/Wnt is produced, an abnormally high concentration of EGL-20 occurs, which prevents anterior polarization of P7.p, and causes ectopic vulval tissue to form at P8.p.

Mentions: Given the Ror/CAM-1-dependent localization of EGL-20/Wnt to the posterior CAN axon, the ability of CAM-1 to bind EGL-20 in vitro [7], and the requirement for only its Wnt-binding extracellular domain for CAM-1 to inhibit Wnt signaling from the CANs, it is possible that Wnt sequestration is part of the mechanism by which the CAN axons regulate epidermal patterning (Figure 9). Our data indicate that if Ror/CAM-1 is absent or if the posterior CAN axon does not grow to a sufficient length, the extracellular distribution of EGL-20/Wnt is altered. In these cases, in a simple model, the EGL-20/Wnt that is displaced from the CAN axons would be available to cause excess EGL-20 signaling in the epidermal progenitors, thereby perturbing normal Wnt patterning. Although only a small fraction of the total EGL-20/Wnt punctae appear to be bound to the posterior CAN axons, there are several possible scenarios in which this pool might be critical in determining the nature and strength of epidermal progenitor Wnt responses. First, many of the EGL-20/Wnt punctae that we detected at other locations might not be truly “free” and able to stimulate epidermal progenitors. They may be bound to other cells or trapped in the extracellular space. Thus, if the EGL-20/Wnt released from the posterior CAN axons is more diffusible than the other EGL-20, it may have a potent ability to change the pattern of epidermal progenitor responses to Wnts. Alternatively, the rectal cells may produce distinct forms of EGL-20/Wnt, with distinct abilities to bind and signal through different EGL-20 receptor complexes. Perhaps a form of EGL-20/Wnt that is specific for the epidermal progenitors is also preferentially sequestered by the CANs, endowing the CANs with a unique ability to regulate epidermal progenitor responses to EGL-20.


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)

Model for neuronal control of axial patterning by Wnts.(A) In wild-type animals, EGL-20/Wnt (orange) (and possibly CWN-1/Wnt [green]) is sequestered by the Ror/CAM-expressing posterior CAN axons. At the end of the L2 larval stage, this sequestration allows MOM-2 and LIN-44 Wnts (blue) to reorient and polarize P7.p towards the anterior (horizontal arrows). During the L3 larval stage, anterior-facing P7.p divides with the mirror image pattern of P5.p, and P8.p does not receive sufficient Wnt or EGF signaling to adopt a vulval fate. (B) If the posterior CAN axons do not extend far enough into the posterior body, where EGL-20/Wnt is produced, an abnormally high concentration of EGL-20 occurs, which prevents anterior polarization of P7.p, and causes ectopic vulval tissue to form at P8.p.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-1001465-g009: Model for neuronal control of axial patterning by Wnts.(A) In wild-type animals, EGL-20/Wnt (orange) (and possibly CWN-1/Wnt [green]) is sequestered by the Ror/CAM-expressing posterior CAN axons. At the end of the L2 larval stage, this sequestration allows MOM-2 and LIN-44 Wnts (blue) to reorient and polarize P7.p towards the anterior (horizontal arrows). During the L3 larval stage, anterior-facing P7.p divides with the mirror image pattern of P5.p, and P8.p does not receive sufficient Wnt or EGF signaling to adopt a vulval fate. (B) If the posterior CAN axons do not extend far enough into the posterior body, where EGL-20/Wnt is produced, an abnormally high concentration of EGL-20 occurs, which prevents anterior polarization of P7.p, and causes ectopic vulval tissue to form at P8.p.
Mentions: Given the Ror/CAM-1-dependent localization of EGL-20/Wnt to the posterior CAN axon, the ability of CAM-1 to bind EGL-20 in vitro [7], and the requirement for only its Wnt-binding extracellular domain for CAM-1 to inhibit Wnt signaling from the CANs, it is possible that Wnt sequestration is part of the mechanism by which the CAN axons regulate epidermal patterning (Figure 9). Our data indicate that if Ror/CAM-1 is absent or if the posterior CAN axon does not grow to a sufficient length, the extracellular distribution of EGL-20/Wnt is altered. In these cases, in a simple model, the EGL-20/Wnt that is displaced from the CAN axons would be available to cause excess EGL-20 signaling in the epidermal progenitors, thereby perturbing normal Wnt patterning. Although only a small fraction of the total EGL-20/Wnt punctae appear to be bound to the posterior CAN axons, there are several possible scenarios in which this pool might be critical in determining the nature and strength of epidermal progenitor Wnt responses. First, many of the EGL-20/Wnt punctae that we detected at other locations might not be truly “free” and able to stimulate epidermal progenitors. They may be bound to other cells or trapped in the extracellular space. Thus, if the EGL-20/Wnt released from the posterior CAN axons is more diffusible than the other EGL-20, it may have a potent ability to change the pattern of epidermal progenitor responses to Wnts. Alternatively, the rectal cells may produce distinct forms of EGL-20/Wnt, with distinct abilities to bind and signal through different EGL-20 receptor complexes. Perhaps a form of EGL-20/Wnt that is specific for the epidermal progenitors is also preferentially sequestered by the CANs, endowing the CANs with a unique ability to regulate epidermal progenitor responses to EGL-20.

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