The BMP pathway is essential for re-specification and maintenance of the dorsoventral axis in regenerating and intact planarians

The Wingless/Integrated (Wnt) signaling pathway controls multiple events during development and homeostasis. It comprises multiple branches, mainly classified according to their dependence on β-catenin activation. The Wnt/β-catenin branch is essential for the establishment of the embryonic anteroposterior (AP) body axis throughout the phylogenetic tree. It is also required for AP axis establishment during planarian regeneration. Wnt/β-catenin-independent signaling encompasses several different pathways, of which the most extensively studied is the planar cell polarity (PCP) pathway, which is responsible for planar polarization of cell structures within an epithelial sheet. Dishevelled (Dvl) is the hub of Wnt signaling because it regulates and channels the Wnt signal into every branch. Here, we analyze the role of Schmidtea mediterranea Dvl homologs (Smed-dvl-1 and Smed-dvl-2) using gene silencing. We demonstrate that in addition to a role in AP axis specification, planarian Dvls are involved in at least two different β-catenin-independent processes. First, they are essential for neural connectivity through Smed-wnt5 signaling. Second, Smed-dvl-2, together with the S. mediterranea homologs of Van-Gogh (Vang) and Diversin (Div), is required for apical positioning of the basal bodies of epithelial cells. These data represent evidence not only of the function of the PCP network in lophotrocozoans but of the involvement of the PCP core elements Vang and Div in apical positioning of the cilia.neural patterning | axial polarity | cilia basal body W ingless/Integrated (Wnt) signaling controls multiple events, including cell migration, planar cell polarity (PCP), and stem cell self-renewal (1, 2). It acts through two main pathways: the canonical or β-catenin-dependent pathway and the noncanonical or β-catenin-independent pathways, which include the PCP and Wnt/calcium pathways. Dishevelled (Dvl) is common to all three pathways (3). In the β-catenin-dependent pathway, Dvl is recruited by the receptor Frizzled (Fz), promoting disassembly of the β-catenin destruction complex through the subsequent recruitment of Axin. As a consequence, β-catenin translocates to the nucleus, where it acts as a master regulator. A common role of the β-catenin/Wnt pathway is in establishing the anteroposterior (AP) axis during development (4). PCP signals are transmitted from cell to cell and are responsible for the polarization of cell structures. During PCP signaling, Dvl is also recruited by a Fz receptor and promotes the asymmetrical localization of the PCP core proteins within the cell, such that the Fz-Dvl-Diversin (Div)/-Diego (Dgo) complex is oppositely localized to the Strabismus (Stbm)/Van-Gogh (Vang)-Prickle (Pk) complex. The asymmetrical subcellular localization of these elements in an epithelial sheet directs cytoskeletal reorganization that results, for instance, in a hair emerging solely from the distal edge of the cell (5-7). The same mechanism is used in mesenchymal cells to direct cell movement and migration during gastrulat...

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“…Planarians of the asexual strain of S. mediterranea were collected in Montjuïch, Barcelona, Spain and were maintained as described (34).…”

Section: Methodsmentioning

confidence: 99%

Dishevelled is essential for neural connectivity and planar cell polarity in planarians

Almuedo-Castillo

Saló

Adell

2011

Proc. Natl. Acad. Sci. U.S.A.

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“…For colorimetric whole-mount in situ hybridization (WISH) analyses, animals were processed using an In situ Pro hybridization robot (Abimed/Intavis), as previously described (Molina et al, 2007;Umesono et al, 1997). For fluorescent whole-mount in situ hybridization (FISH), planarians were fixed and stained as previously described (Pearson et al, 2009).…”

Section: Gene Expression Analysismentioning

confidence: 99%

Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis

2016

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The β-catenin-dependent Wnt pathway exerts multiple contextdependent roles in embryonic and adult tissues. In planarians, β-catenin-1 is thought to specify posterior identities through the generation of an anteroposterior gradient. However, the existence of such a gradient has not been directly demonstrated. Here, we use a specific polyclonal antibody to demonstrate that nuclear β-CATENIN-1 exists as an anteroposterior gradient from the pre-pharyngeal region to the tail of the planarian Schmidtea polychroa. High levels in the posterior region steadily decrease towards the pre-pharyngeal region but then increase again in the head region. During regeneration, β-CATENIN-1 is nuclearized in both anterior and posterior blastemas, but the canonical WNT1 ligand only influences posterior nuclearization. Additionally, β-catenin-1 is required for proper anterior morphogenesis, consistent with the high levels of nuclear β-CATENIN-1 observed in this region. We further demonstrate that β-CATENIN-1 is abundant in developing and differentiated organs, and is particularly required for the specification of the germline. Altogether, our findings provide the first direct evidence of an anteroposterior nuclear β-CATENIN-1 gradient in adult planarians and uncover novel, context-dependent roles for β-catenin-1 during anterior regeneration and organogenesis.

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“…Positive controls (data not shown) for all ISH were performed with smed_noggin1 (Molina et al, 2007) and smedwi-2 (Reddien et al, 2005a).…”

Section: Whole-mount In Situ Hybridization Experimentsmentioning

confidence: 99%

Diverse miRNA spatial expression patterns suggest important roles in homeostasis and regeneration in planarians

González‐Estévez¹,

Arseni²,

Thambyrajah³

et al. 2009

Int. J. Dev. Biol.

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miRNAs are an important class of non-protein coding small RNAs whose specific functions in animals are rapidly being elucidated. It is clear that miRNAs can play crucial roles in stem cell maintenance, cell fate determination and differentiation. We use planarians, which possess a large population of pluripotent somatic stem cells, as a powerful model system to study many aspects of stem cell biology and regeneration. In particular we wish to investigate the regulatory role miRNAs may have in planarian stem cell self renewal, proliferation and differentiation. Here, we characterized the differential spatial patterns of expression of miRNAs in whole and regenerating planarians by in situ hybridization to nascent miRNA transcripts. These miRNA expression patterns are the first which have been determined for a Lophotrocozoan animal. We have characterized the expression patterns of 42 miRNAs in adult planarians, constituting a complete range of tissue specific expression patterns. We also followed miRNA expression during planarian regeneration. The majority of planarian miRNAs were expressed either in areas where stem cells (neoblasts) are located and/or in the nervous system. Some miRNAs were definitively expressed in stem cells and dividing cells as confirmed by in situ hybridisation after irradiation. We also found miRNAs to be expressed in germ stem cells of the sexual strain. Together, these data suggest an important role for miRNAs in stem cell regulation and in neural cell differentiation in planarians.

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The BMP pathway is essential for re-specification and maintenance of the dorsoventral axis in regenerating and intact planarians

Cited by 154 publications

References 41 publications

Dishevelled is essential for neural connectivity and planar cell polarity in planarians

Dishevelled is essential for neural connectivity and planar cell polarity in planarians

Localization of planarian β-CATENIN-1 reveals multiple roles during anterior-posterior regeneration and organogenesis

Diverse miRNA spatial expression patterns suggest important roles in homeostasis and regeneration in planarians

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