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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

Wnt signaling and epidermal patterning in C. elegans.(A) A wild-type C. elegans adult hermaphrodite. Scale bar is 100 µm. (B) During the L2 larval stage, LIN-3/EGF from pre-anchor cell/ventral uterine precursor cells (not shown) cooperates with a gradient of EGL-20/Wnt (orange) from rectal cells and CWN-1/Wnt (green) from posterior muscle and neurons to cause six epidermal cells to become vulval progenitors (P3.p–P8.p). 50% of the time, P3.p does not receive sufficient Wnt signaling and adopts the “F” fate (also known as the 4° fate) and fuses with a hypodermal syncytium called hyp7. EGL-20/Wnt also polarizes P5.p and P7.p so that they face posteriorly (horizontal arrows). The epidermal cells normally touch each other, but are drawn apart to facilitate depiction of muscle and neurons. (C) At the end of the L2 larval stage, anchor cell-produced MOM-2 and LIN-44 Wnts (blue) reorient P7.p towards the anterior (horizontal arrows). During the L3 larval stage, LIN-3/EGF (purple) from the anchor cell induces the 1° vulval fate in P6.p, which is facilitated by EGL-20 and CWN-1 Wnts. P5.p and P7.p adopt 2° vulval fates because of the activation of LIN-12/Notch via a lateral signal from P6.p. (D) During the L3–L4 larval stages, vulval progenitor cells (Pn.p) divide to generate Pn.px cells, with P5.p–P7.p undergoing two additional rounds of cell division (to ultimately make Pn.pxxx cells). Because of the opposite polarities of P5.p and P7.p, their asymmetrically dividing progeny generate mirror image patterns. By the early L4 stage, a 22-cell vulva is generated. The Pn.px progeny of P3.p, P4.p, and P8.p fuse with hyp7 (3° fate).
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pbio-1001465-g001: Wnt signaling and epidermal patterning in C. elegans.(A) A wild-type C. elegans adult hermaphrodite. Scale bar is 100 µm. (B) During the L2 larval stage, LIN-3/EGF from pre-anchor cell/ventral uterine precursor cells (not shown) cooperates with a gradient of EGL-20/Wnt (orange) from rectal cells and CWN-1/Wnt (green) from posterior muscle and neurons to cause six epidermal cells to become vulval progenitors (P3.p–P8.p). 50% of the time, P3.p does not receive sufficient Wnt signaling and adopts the “F” fate (also known as the 4° fate) and fuses with a hypodermal syncytium called hyp7. EGL-20/Wnt also polarizes P5.p and P7.p so that they face posteriorly (horizontal arrows). The epidermal cells normally touch each other, but are drawn apart to facilitate depiction of muscle and neurons. (C) At the end of the L2 larval stage, anchor cell-produced MOM-2 and LIN-44 Wnts (blue) reorient P7.p towards the anterior (horizontal arrows). During the L3 larval stage, LIN-3/EGF (purple) from the anchor cell induces the 1° vulval fate in P6.p, which is facilitated by EGL-20 and CWN-1 Wnts. P5.p and P7.p adopt 2° vulval fates because of the activation of LIN-12/Notch via a lateral signal from P6.p. (D) During the L3–L4 larval stages, vulval progenitor cells (Pn.p) divide to generate Pn.px cells, with P5.p–P7.p undergoing two additional rounds of cell division (to ultimately make Pn.pxxx cells). Because of the opposite polarities of P5.p and P7.p, their asymmetrically dividing progeny generate mirror image patterns. By the early L4 stage, a 22-cell vulva is generated. The Pn.px progeny of P3.p, P4.p, and P8.p fuse with hyp7 (3° fate).

Mentions: In Caenorhabditis elegans, the generation of a vulva in the middle of the anterior–posterior axis has become a paradigm for understanding how Wnt and EGF family growth factors generate specific patterns at precise locations (reviewed in [11]) (Figure 1A). Vulval organogenesis begins with the mid-body generation of six vulval progenitors from 11 blast cells. These progenitors (P3.p–P8.p) are specified by two posteriorly derived Wnt gradients (EGL-20 and CWN-1 [orange and green, respectively, in Figure 1]) [7],[12]–[15], with EGL-20 also polarizing some of the progenitors to face towards the posterior (e.g., P5.p and P7.p) [16] (Figure 1B). Later, mid-body-produced Wnts (LIN-44 and MOM-2 [blue in Figure 1]) reverse P7.p polarity so that P5.p and P7.p face each other and subsequently divide with mirror image symmetry (Figure 1C and 1D) [16],[17]. With the help of the posterior Wnts (EGL-20 and CWN-1), centrally produced EGF (purple in Figure 1) instructs P6.p to adopt a 1° fate, divide three times, and form the vulval lumen that attaches to the uterus (Figure 1C and 1D) [7],[11],[18]–[20]. In parallel, P6.p activates Notch signaling in adjacent P5.p and P7.p to induce 2° fates, which, after three rounds of division, create the symmetrical sides of the vulva that attach the organ to the epidermis (Figure 1C and 1D). Insufficient signaling alters vulval patterning and reduces the amount of vulval tissue [11],[21]. Excessive signaling also alters vulval patterning and, if it occurs at certain axial positions, generates ectopic, non-functional vulvae, which can interfere with normal positioning of muscles and neurons that promote egg-laying [19],[21]–[24].


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)

Wnt signaling and epidermal patterning in C. elegans.(A) A wild-type C. elegans adult hermaphrodite. Scale bar is 100 µm. (B) During the L2 larval stage, LIN-3/EGF from pre-anchor cell/ventral uterine precursor cells (not shown) cooperates with a gradient of EGL-20/Wnt (orange) from rectal cells and CWN-1/Wnt (green) from posterior muscle and neurons to cause six epidermal cells to become vulval progenitors (P3.p–P8.p). 50% of the time, P3.p does not receive sufficient Wnt signaling and adopts the “F” fate (also known as the 4° fate) and fuses with a hypodermal syncytium called hyp7. EGL-20/Wnt also polarizes P5.p and P7.p so that they face posteriorly (horizontal arrows). The epidermal cells normally touch each other, but are drawn apart to facilitate depiction of muscle and neurons. (C) At the end of the L2 larval stage, anchor cell-produced MOM-2 and LIN-44 Wnts (blue) reorient P7.p towards the anterior (horizontal arrows). During the L3 larval stage, LIN-3/EGF (purple) from the anchor cell induces the 1° vulval fate in P6.p, which is facilitated by EGL-20 and CWN-1 Wnts. P5.p and P7.p adopt 2° vulval fates because of the activation of LIN-12/Notch via a lateral signal from P6.p. (D) During the L3–L4 larval stages, vulval progenitor cells (Pn.p) divide to generate Pn.px cells, with P5.p–P7.p undergoing two additional rounds of cell division (to ultimately make Pn.pxxx cells). Because of the opposite polarities of P5.p and P7.p, their asymmetrically dividing progeny generate mirror image patterns. By the early L4 stage, a 22-cell vulva is generated. The Pn.px progeny of P3.p, P4.p, and P8.p fuse with hyp7 (3° fate).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3539944&req=5

pbio-1001465-g001: Wnt signaling and epidermal patterning in C. elegans.(A) A wild-type C. elegans adult hermaphrodite. Scale bar is 100 µm. (B) During the L2 larval stage, LIN-3/EGF from pre-anchor cell/ventral uterine precursor cells (not shown) cooperates with a gradient of EGL-20/Wnt (orange) from rectal cells and CWN-1/Wnt (green) from posterior muscle and neurons to cause six epidermal cells to become vulval progenitors (P3.p–P8.p). 50% of the time, P3.p does not receive sufficient Wnt signaling and adopts the “F” fate (also known as the 4° fate) and fuses with a hypodermal syncytium called hyp7. EGL-20/Wnt also polarizes P5.p and P7.p so that they face posteriorly (horizontal arrows). The epidermal cells normally touch each other, but are drawn apart to facilitate depiction of muscle and neurons. (C) At the end of the L2 larval stage, anchor cell-produced MOM-2 and LIN-44 Wnts (blue) reorient P7.p towards the anterior (horizontal arrows). During the L3 larval stage, LIN-3/EGF (purple) from the anchor cell induces the 1° vulval fate in P6.p, which is facilitated by EGL-20 and CWN-1 Wnts. P5.p and P7.p adopt 2° vulval fates because of the activation of LIN-12/Notch via a lateral signal from P6.p. (D) During the L3–L4 larval stages, vulval progenitor cells (Pn.p) divide to generate Pn.px cells, with P5.p–P7.p undergoing two additional rounds of cell division (to ultimately make Pn.pxxx cells). Because of the opposite polarities of P5.p and P7.p, their asymmetrically dividing progeny generate mirror image patterns. By the early L4 stage, a 22-cell vulva is generated. The Pn.px progeny of P3.p, P4.p, and P8.p fuse with hyp7 (3° fate).
Mentions: In Caenorhabditis elegans, the generation of a vulva in the middle of the anterior–posterior axis has become a paradigm for understanding how Wnt and EGF family growth factors generate specific patterns at precise locations (reviewed in [11]) (Figure 1A). Vulval organogenesis begins with the mid-body generation of six vulval progenitors from 11 blast cells. These progenitors (P3.p–P8.p) are specified by two posteriorly derived Wnt gradients (EGL-20 and CWN-1 [orange and green, respectively, in Figure 1]) [7],[12]–[15], with EGL-20 also polarizing some of the progenitors to face towards the posterior (e.g., P5.p and P7.p) [16] (Figure 1B). Later, mid-body-produced Wnts (LIN-44 and MOM-2 [blue in Figure 1]) reverse P7.p polarity so that P5.p and P7.p face each other and subsequently divide with mirror image symmetry (Figure 1C and 1D) [16],[17]. With the help of the posterior Wnts (EGL-20 and CWN-1), centrally produced EGF (purple in Figure 1) instructs P6.p to adopt a 1° fate, divide three times, and form the vulval lumen that attaches to the uterus (Figure 1C and 1D) [7],[11],[18]–[20]. In parallel, P6.p activates Notch signaling in adjacent P5.p and P7.p to induce 2° fates, which, after three rounds of division, create the symmetrical sides of the vulva that attach the organ to the epidermis (Figure 1C and 1D). Insufficient signaling alters vulval patterning and reduces the amount of vulval tissue [11],[21]. Excessive signaling also alters vulval patterning and, if it occurs at certain axial positions, generates ectopic, non-functional vulvae, which can interfere with normal positioning of muscles and neurons that promote egg-laying [19],[21]–[24].

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