Talk:Developmental Signals - Wnt

2010

beta-Catenin regulates intercellular signalling networks and cell-type specific transcription in the developing mouse midbrain-rhombomere 1 region

PLoS One. 2010 Jun 3;5(6):e10881.

Chilov D, Sinjushina N, Saarimäki-Vire J, Taketo MM, Partanen J.

Institute of Biotechnology, University of Helsinki, Helsinki, Finland. Abstract beta-Catenin is a multifunctional protein involved in both signalling by secreted factors of Wnt family and regulation of the cellular architecture. We show that beta-catenin stabilization in mouse midbrain-rhombomere 1 region leads to robust up-regulation of several Wnt signalling target genes, including Fgf8. Suggestive of direct transcriptional regulation of the Fgf8 gene, beta-catenin stabilization resulted in Fgf8 up-regulation also in other tissues, specifically in the ventral limb ectoderm. Interestingly, stabilization of beta-catenin rapidly caused down-regulation of the expression of Wnt1 itself, suggesting a negative feedback loop. The changes in signal molecule expression were concomitant with deregulation of anterior-posterior and dorso-ventral patterning. The transcriptional regulatory functions of beta-catenin were confirmed by beta-catenin loss-of-function experiments. Temporally controlled inactivation of beta-catenin revealed a cell-autonomous role for beta-catenin in the maintenance of cell-type specific gene expression in the progenitors of midbrain dopaminergic neurons. These results highlight the role of beta-catenin in establishment of neuroectodermal signalling centers, promoting region-specific gene expression and regulation of cell fate determination.

PMID: 20532162 http://www.ncbi.nlm.nih.gov/pubmed/20532162

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010881

Wnt1 signaling has been implicated as one factor involved in neural crest-derived melanocyte (NC-M) development. http://www.ncbi.nlm.nih.gov/pubmed/10963668

=Neural crest-directed gene transfer demonstrates Wnt1 role in melanocyte expansion and differentiation during mouse development

Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):10050-5. Dunn KJ, Williams BO, Li Y, Pavan WJ.

Genetic Disease Research Branch, National Human Genome Research Institute, and Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA. Abstract Wnt1 signaling has been implicated as one factor involved in neural crest-derived melanocyte (NC-M) development. Mice deficient for both Wnt1 and Wnt3a have a marked deficiency in trunk neural crest derivatives including NC-Ms. We have used cell lineage-directed gene targeting of Wnt signaling genes to examine the effects of Wnt signaling in mouse neural crest development. Gene expression was directed to cell lineages by infection with subgroup A avian leukosis virus vectors in lines of transgenic mice that express the retrovirus receptor tv-a. Transgenic mice with tva in either nestin-expressing neural precursor cells (line Ntva) or dopachrome tautomerase (DCT)-expressing melanoblasts (line DCTtva) were analyzed. We overstimulated Wnt signaling in two ways: directed gene transfer of Wnt1 to Ntva(+) cells and transfer of beta-catenin to DCTtva(+) NC-M precursor cells. In both methods, NC-M expansion and differentiation were effected. Significant increases were observed in the number of NC-Ms [melanin(+) and tyrosinase-related protein 1 (TYRP1)(+) cells], the differentiation of melanin(-) TYRP1(+) cells to melanin(+) TYRP1(+) NC-Ms, and the intensity of pigmentation per NC-M. These data are consistent with Wnt1 signaling being involved in both expansion and differentiation of migrating NC-Ms in the developing mouse embryo. The use of lineage-directed gene targeting will allow the dissection of signaling molecules involved in NC development and is adaptable to other mammalian developmental systems.

Endothelial specific stabilization of Wnt/beta-catenin signaling alters early vascular development in the embryo by upregulating Dll4/Notch signaling (Dev Cell, June 2010).

Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation (Blood, Jan 2009).

The nuclear import of Frizzled2-C by Importins-beta11 and alpha2 promotes postsynaptic development. Therefore, Wnt-activated growth of the post-synaptic membrane is mediated by the synapse-to-nucleus translocation and active nuclear import of Fz2-C (Nat Neurosci, August 2010).