An evolutionary conserved role of Wnt signaling in stem cell fate decision

Abstract

Wnt/Frizzled/ss-catenin-based signaling systems play diverse roles in metazoan development, being involved not only in the establishment of body axes in embryogenesis but also in regulating stem cell fate in mammalian post-embryonic development. We have studied the role the canonical Wnt cascade plays in stem cell fate determination in Hydractinia, a member of the ancient metazoan phylum Cnidaria, by analyzing two key molecules in this pathway, frizzled and ss-catenin, and blocking GSK-3. Generally, frizzled was expressed in cells able to divide but absent in post-mitotic, terminally differentiated cells such as nerve cells and nematocytes. Transcripts of frizzled were identified in all embryonic stages beginning with maternal transcripts in the oocyte. Following gastrulation and in the planula larva, frizzled expression concentrated in the central endodermal mass from which the first interstitial stem cells and their derivatives arise. In post-metamorphic development, high levels of frizzled transcripts were detected in interstitial stem cells. Activating downstream events of the Wnt-cascade in the post-metamorphic life phase by blocking GSK-3 with paullones induced recruitment of nematocytes and nerve cells from the pool of interstitial stem cells. Terminal differentiation was preceded by an initial burst of proliferation of frizzled-positive i-cells. In activated i-cells, ss-catenin appeared in the cytoplasm, later in the nucleus. It was subsequently again observed in the cytoplasm and eventually faded out during terminal differentiation. Our results suggest an ancient role of Wnt signaling in stem cell fate determination.

Glucagon-like Peptide-1 Activation of TCF7L2-dependent Wnt Signaling Enhances Pancreatic Beta Cell Proliferation

“…2) Components of the Wnt signaling pathway are known to be expressed in the pancreas during development, and experimentally induced genetic disruption of Wnt signaling impairs pancreas growth and functions (21,22,24,34). Wnt signaling is an important pathway in the maintenance of the proliferation and the differentiation of embryonic and somatic stem cells (23,(35)(36)(37)(38)(39) Table S1). …”

Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis

“…36,37 A domain present only in enteropeptidase, MAM, is responsible for protein oligomerization in meprin proteases 38 and tyrosine phosphatase mu, 39 while Frizzled domains function as receptors for Wnt proteins during embryonic development and stem cell self-renewal. 40 Utilizing the domain composition of the stem region in tandem with phylogenetic analysis of the serine protease domain of the TTSPs has enabled sub-familial classification. 14 The largest of the sub-families, HAT/DESC (Differentially Expressed in Squamous cell Carcinoma) consists of the proteases HAT, DESC1-4 10,41,42 and HATlike 3-5.…”

The Wnt code: cnidarians signal the way

“…Also data from Hydractinia echinata, a colonial marine hydrozoan species, support the function of Wnt signalling in axial patterning. Inhibition of GSK-3b activity with alsterpaullone causes ectopic axes in embryos and the formation of ectopic tentacles in adult polyps of the colony (Muller et al, 2004a, b;Plickert et al, 2006;Teo et al, 2006). In Hydractinia, Wnt/b-catenin signalling , while the Wnt-anatagonist hydkk1/2/4 is expressed in the body column (Guder et al, 2006).…”

“…In Hydractinia, Wnt/b-catenin signalling , while the Wnt-anatagonist hydkk1/2/4 is expressed in the body column (Guder et al, 2006). Cnidarian Wnt signalling C Guder et al also promotes stem cell fate determination (Teo et al, 2006).…”