Multicellularity, stem cells, and the neoblasts of the planarian Schmidtea mediterranea

Alvarado, Alejandro Sánchez; Kang, Hyunjin

doi:10.1016/j.yexcr.2005.03.020

Cited by 64 publications

(33 citation statements)

References 63 publications

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“…Twelve innexin clones (smedinx-1-12) were identified in the planarian S. mediterranea Among planarian species, S. mediterranea is the most convenient model in which to perform molecular and genetic analyses Saló, 2006;Sánchez Alvarado, 2006;Sánchez Alvarado and Kang, 2005). Twelve cDNAs coding for innexins were identified in two public S. mediterranea databases Zayas et al, 2005) and numbered smedinx-1 to smedinx-12 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Likewise, exciting recent data have linked ion and small-molecule transport to regenerative ability in vertebrates (Adams et al, 2007;Nuccitelli, 2003;Zhao et al, 2006). Thus, GJC might provide an ancient and powerful mechanism for mediating the complex interplay of regulatory signals among differentiated and stem cells in multicellular systems (Sánchez Alvarado and Kang, 2005). Further molecular analyses of GJ roles in planaria and vertebrate systems will provide crucial opportunities to understand the evolution of morphogenetic controls as well as identifying novel therapeutic targets for manipulating stem cell behaviors in biomedical settings.…”

Section: Discussionmentioning

confidence: 99%

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smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

Oviedo¹,

Levin²

2007

Development

104

102

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The largely unknown mechanisms that regulate adult stem cells probably involve signals from neighboring differentiated cells. Gap junction channels providing direct cell-cell communication via small molecules are a crucial component of morphogenesis and normal physiology. However, no specific gap junction protein has yet been functionally linked to adult/somatic stem cell behavior in vivo or to organ regeneration. We report the identification and characterization of smedinx-11 -an innexin gap junction channel gene expressed in the adult stem cells (neoblasts) of the planarian Schmidtea mediterranea. smedinx-11 RNAi treatment inhibits regeneration and abrogates neoblast maintenance. Moreover, smedinx-11 expression is enriched in an irradiation-sensitive subpopulation ('X2') and is required for proper expression of other stem cell-specific markers. Analyses of the smedinx-11 downregulation phenotype revealed a striking anterior-posterior neoblast gradient. Our data demonstrate a novel role for gap junction proteins and suggest gap junction-mediated signaling as a new and tractable control point for adult, somatic stem cell regulation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

Oviedo¹,

Levin²

2007

Development

104

102

View full text Add to dashboard Cite

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“…The latter represents 20-30% of the total cells of an adult planarian and defines cell cycle kinetics, migration and fluxes of differentiation. (33,77,89) As mentioned above, the non-amenability of planarians to classic genetic analysis required alternative tools. The first tool to be developed was RNA-mediated genetic interference (RNAi).…”

Section: New Molecular Tools For Determining Planarian Regenerationmentioning

confidence: 99%

The power of regeneration and the stem‐cell kingdom: freshwater planarians (Platyhelminthes)

2006

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The great powers of regeneration shown by freshwater planarians, capable of regenerating a complete organism from any tiny body fragment, have attracted the interest of scientists throughout history. In 1814, Dalyell concluded that planarians could "almost be called immortal under the edge of the knife". Equally impressive is the developmental plasticity of these platyhelminthes, including continuous growth and fission (asexual reproduction) in well-fed organisms, and shrinkage (degrowth) during prolonged starvation. The source of their morphological plasticity and regenerative capability is a stable population of totipotent stem cells--"neoblasts"; this is the only cell type in the adult that has mitotic activity and differentiates into all cell types. This cellular feature is unique to planarians in the Bilateria clade. Over the last fifteen years, molecular studies have begun to reveal the role of developmental genes in regeneration, although it would be premature to propose a molecular model for planarian regeneration. Genomic and proteomic data are essential in answering some of the fundamental questions concerning this remarkable morphological plasticity. Such information should also pave the way to understanding the genetic pathways associated with metazoan somatic stem-cell regulation and pattern formation.

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“…This regenerative ability is made possible by a large population of pluripotent adult stem cells (ASCs) (Sánchez Alvarado and Kang, 2005;Wagner et al, 2011). S. med is a constitutive asexual adult and is amenable to gene-function studies by use of RNA interference (RNAi), which is fed to adult animals and subsequently spreads to all tissues, including neurons (Sánchez Alvarado and Newmark, 1999).…”

Section: Introductionmentioning

confidence: 99%

Transcription factors lhx1/5-1 and pitx are required for the maintenance and regeneration of serotonergic neurons in planarians

2013

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SUMMARYIn contrast to most adult organisms, freshwater planarians can regenerate any injured body part, including their entire nervous system. This allows for the analysis of genes required for both the maintenance and regeneration of specific neural subtypes. In addition, the loss of specific neural subtypes may uncover previously unknown behavioral roles for that neural population in the context of the adult animal. Here we show that two homeodomain transcription factor homologs, Smed-lhx1/5-1 and Smed-pitx, are required for the maintenance and regeneration of serotonergic neurons in planarians. When either lhx1/5-1 or pitx was knocked down by RNA interference, the expression of multiple canonical markers for serotonergic neurons was lost. Surprisingly, the loss of serotonergic function uncovered a role for these neurons in the coordination of motile cilia on the ventral epidermis of planarians that are required for their nonmuscular gliding locomotion. Finally, we show that in addition to its requirement in serotonergic neurons, Smed-pitx is required for proper midline patterning during regeneration, when it is required for the expression of the midline-organizing molecules Smed-slit in the anterior and Smed-wnt1 in the posterior.

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Multicellularity, stem cells, and the neoblasts of the planarian Schmidtea mediterranea

Cited by 64 publications

References 63 publications

smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

smedinx-11is a planarian stem cell gap junction gene required for regeneration and homeostasis

The power of regeneration and the stem‐cell kingdom: freshwater planarians (Platyhelminthes)

Transcription factors lhx1/5-1 and pitx are required for the maintenance and regeneration of serotonergic neurons in planarians

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