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Repulsive cues combined with physical barriers and cell-cell adhesion determine progenitor cell positioning during organogenesis.

Paksa A, Bandemer J, Hoeckendorf B, Razin N, Tarbashevich K, Minina S, Meyen D, Biundo A, Leidel SA, Peyrieras N, Gov NS, Keller PJ, Raz E - Nat Commun (2016)

Bottom Line: Using primordial germ cells that participate in gonad formation, we present the developmental mechanisms maintaining a motile progenitor cell population at the site where the organ develops.Employing high-resolution live-cell microscopy, we find that repulsive cues coupled with physical barriers confine the cells to the correct bilateral positions.This analysis revealed that cell polarity changes on interaction with the physical barrier and that the establishment of compact clusters involves increased cell-cell interaction time.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cell Biology, ZMBE, Von-Esmarch-Street 56, 48149 Muenster, Germany.

ABSTRACT
The precise positioning of organ progenitor cells constitutes an essential, yet poorly understood step during organogenesis. Using primordial germ cells that participate in gonad formation, we present the developmental mechanisms maintaining a motile progenitor cell population at the site where the organ develops. Employing high-resolution live-cell microscopy, we find that repulsive cues coupled with physical barriers confine the cells to the correct bilateral positions. This analysis revealed that cell polarity changes on interaction with the physical barrier and that the establishment of compact clusters involves increased cell-cell interaction time. Using particle-based simulations, we demonstrate the role of reflecting barriers, from which cells turn away on contact, and the importance of proper cell-cell adhesion level for maintaining the tight cell clusters and their correct positioning at the target region. The combination of these developmental and cellular mechanisms prevents organ fusion, controls organ positioning and is thus critical for its proper function.

No MeSH data available.


Related in: MedlinePlus

Progenitor cell positioning at target site.An illustration demonstrating the interplay of repulsive cues and physical barriers within the embryo that govern the positioning of PGCs at the site of the developing gonad. At the time of PGC clusters initial formation, the guidance cue cxcl12a RNA is expressed at the migration target (yellow). In the following stages the chemokine is not expressed, calling for other mechanisms maintaining the position of the germline progenitors. In wild-type embryos dorsal repulsive tissues (somites expressing LPPs in magenta) inhibit the dorsal migration of PGC clusters, while the developing gut (red) acts as a physical barrier separating the clusters, thereby contributing to the formation of distinct cell clusters at the site of developing organ. In embryos deficient for the function of LPPs or lacking the physical barrier, the PGCs exhibit abnormal positioning.
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f8: Progenitor cell positioning at target site.An illustration demonstrating the interplay of repulsive cues and physical barriers within the embryo that govern the positioning of PGCs at the site of the developing gonad. At the time of PGC clusters initial formation, the guidance cue cxcl12a RNA is expressed at the migration target (yellow). In the following stages the chemokine is not expressed, calling for other mechanisms maintaining the position of the germline progenitors. In wild-type embryos dorsal repulsive tissues (somites expressing LPPs in magenta) inhibit the dorsal migration of PGC clusters, while the developing gut (red) acts as a physical barrier separating the clusters, thereby contributing to the formation of distinct cell clusters at the site of developing organ. In embryos deficient for the function of LPPs or lacking the physical barrier, the PGCs exhibit abnormal positioning.

Mentions: We found that after arriving at the region where the gonad develops, the positioning of the PGCs along the plane studied (transverse plane) is governed by physical and repulsive cues, rather than by chemokine signalling that guided the cells at earlier stages (Fig. 8). The chemokine receptor is known to undergo desensitization, internalization and degradation at domains of high-chemokine abundance5152. Therefore, maintaining the cells within the region of the developing gonad for a long time by employing chemokine signalling would have required strong continuous production of the receptor and its ligand. Employing nearby developing tissues as physical barriers, combined with repulsive cellular domains, could serve this purpose more efficiently. Indeed, localized LPP overexpression converted practically any region in the embryo into a repulsive domain for PGCs. This observation indicates that the substrates for the LPPs are present throughout the embryo during early development, a period at which the relevant phospholipids could be searched for. This finding together with the fact that other developing organs could serve as physical barriers for other migratory cell populations, makes it likely that the two activities described in this work operate in patterning of other organs as well.


Repulsive cues combined with physical barriers and cell-cell adhesion determine progenitor cell positioning during organogenesis.

Paksa A, Bandemer J, Hoeckendorf B, Razin N, Tarbashevich K, Minina S, Meyen D, Biundo A, Leidel SA, Peyrieras N, Gov NS, Keller PJ, Raz E - Nat Commun (2016)

Progenitor cell positioning at target site.An illustration demonstrating the interplay of repulsive cues and physical barriers within the embryo that govern the positioning of PGCs at the site of the developing gonad. At the time of PGC clusters initial formation, the guidance cue cxcl12a RNA is expressed at the migration target (yellow). In the following stages the chemokine is not expressed, calling for other mechanisms maintaining the position of the germline progenitors. In wild-type embryos dorsal repulsive tissues (somites expressing LPPs in magenta) inhibit the dorsal migration of PGC clusters, while the developing gut (red) acts as a physical barrier separating the clusters, thereby contributing to the formation of distinct cell clusters at the site of developing organ. In embryos deficient for the function of LPPs or lacking the physical barrier, the PGCs exhibit abnormal positioning.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837475&req=5

f8: Progenitor cell positioning at target site.An illustration demonstrating the interplay of repulsive cues and physical barriers within the embryo that govern the positioning of PGCs at the site of the developing gonad. At the time of PGC clusters initial formation, the guidance cue cxcl12a RNA is expressed at the migration target (yellow). In the following stages the chemokine is not expressed, calling for other mechanisms maintaining the position of the germline progenitors. In wild-type embryos dorsal repulsive tissues (somites expressing LPPs in magenta) inhibit the dorsal migration of PGC clusters, while the developing gut (red) acts as a physical barrier separating the clusters, thereby contributing to the formation of distinct cell clusters at the site of developing organ. In embryos deficient for the function of LPPs or lacking the physical barrier, the PGCs exhibit abnormal positioning.
Mentions: We found that after arriving at the region where the gonad develops, the positioning of the PGCs along the plane studied (transverse plane) is governed by physical and repulsive cues, rather than by chemokine signalling that guided the cells at earlier stages (Fig. 8). The chemokine receptor is known to undergo desensitization, internalization and degradation at domains of high-chemokine abundance5152. Therefore, maintaining the cells within the region of the developing gonad for a long time by employing chemokine signalling would have required strong continuous production of the receptor and its ligand. Employing nearby developing tissues as physical barriers, combined with repulsive cellular domains, could serve this purpose more efficiently. Indeed, localized LPP overexpression converted practically any region in the embryo into a repulsive domain for PGCs. This observation indicates that the substrates for the LPPs are present throughout the embryo during early development, a period at which the relevant phospholipids could be searched for. This finding together with the fact that other developing organs could serve as physical barriers for other migratory cell populations, makes it likely that the two activities described in this work operate in patterning of other organs as well.

Bottom Line: Using primordial germ cells that participate in gonad formation, we present the developmental mechanisms maintaining a motile progenitor cell population at the site where the organ develops.Employing high-resolution live-cell microscopy, we find that repulsive cues coupled with physical barriers confine the cells to the correct bilateral positions.This analysis revealed that cell polarity changes on interaction with the physical barrier and that the establishment of compact clusters involves increased cell-cell interaction time.

View Article: PubMed Central - PubMed

Affiliation: Institute for Cell Biology, ZMBE, Von-Esmarch-Street 56, 48149 Muenster, Germany.

ABSTRACT
The precise positioning of organ progenitor cells constitutes an essential, yet poorly understood step during organogenesis. Using primordial germ cells that participate in gonad formation, we present the developmental mechanisms maintaining a motile progenitor cell population at the site where the organ develops. Employing high-resolution live-cell microscopy, we find that repulsive cues coupled with physical barriers confine the cells to the correct bilateral positions. This analysis revealed that cell polarity changes on interaction with the physical barrier and that the establishment of compact clusters involves increased cell-cell interaction time. Using particle-based simulations, we demonstrate the role of reflecting barriers, from which cells turn away on contact, and the importance of proper cell-cell adhesion level for maintaining the tight cell clusters and their correct positioning at the target region. The combination of these developmental and cellular mechanisms prevents organ fusion, controls organ positioning and is thus critical for its proper function.

No MeSH data available.


Related in: MedlinePlus