1: Dev Biol. 2004 Nov 15;275(2):325-42. 

A balance between the anti-apoptotic activity of Slug and the apoptotic activity
of msx1 is required for the proper development of the neural crest.

Tribulo C, Aybar MJ, Sanchez SS, Mayor R.

Millennium Nucleus in Developmental Biology, Facultad de Ciencias, Universidad
de Chile, Casilla 653, Santiago, Chile.

We have studied the pattern of programmed cell death in the neural crest and
analyzed how it is controlled by the activity of the transcription factors Slug
and msx1. Our results indicate that apoptosis is more prevalent in the neural
folds than in the rest of the neural ectoderm. Through gain- and
loss-of-function experiments with inducible forms of both Slug and msx1 genes,
we showed that Slug acts as an anti-apoptotic factor whereas msx1 promotes cell
death, either in the neural folds of the whole embryos, in isolated or induced
neural crest and in animal cap assays. The protective effect of expressing Slug
can be reversed by expressing the apoptotic factor Bax, while the apoptosis
promoted by msx1 can be abolished by expressing the Xenopus homologue of Bcl2
(XR11). Furthermore, we show that Slug and msx1 control the transcription of
XR11 and several caspases required for programmed cell death. In addition,
expression of Bax or Bcl2, produced similar effects on the survival of the
neural crest and on the development of its derivatives to those produced by
altering the activity of Slug or msx1. Finally, we show that in the neural
crest, the region of the neural folds where Slug is expressed, cells undergo
less apoptosis, than in the region where the msx1 gene is expressed, which
correspond to cells adjacent to the neural crest. We show that the expression of
Slug and msx1 controls cell death in certain areas of the neural folds, and we
discuss how this equilibrium is necessary to generate sharp boundaries in the
neural crest territory, and to precisely control cell number among neural crest
derivatives.

PMID: 15501222 [PubMed - indexed for MEDLINE]


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2: BMC Dev Biol. 2002 Jul 2;2:8. 

A transcriptional response to Wnt protein in human embryonic carcinoma cells.

Willert J, Epping M, Pollack JR, Brown PO, Nusse R.

Department of Developmental Biology, Howard Hughes Medical Institute, Stanford
University, Stanford, CA 94305 USA. jennifer.willert@cox.net

BACKGROUND: Wnt signaling is implicated in many developmental decisions,
including stem cell control, as well as in cancer. There are relatively few
target genes known of the Wnt pathway. RESULTS: We have identified target genes
of Wnt signaling using microarray technology and human embryonic carcinoma cells
stimulated with active Wnt protein. The ~50 genes upregulated early after Wnt
addition include the previously known Wnt targets Cyclin D1, MYC, ID2 and
betaTRCP. The newly identified targets, which include MSX1, MSX2, Nucleophosmin,
Follistatin, TLE/Groucho, Ubc4/5E2, CBP/P300, Frizzled and REST/NRSF, have
important implications for understanding the roles of Wnts in development and
cancer. The protein synthesis inhibitor cycloheximide blocks induction by Wnt,
consistent with a requirement for newly synthesized beta-catenin protein prior
to target gene activation. The promoters of nearly all the target genes we
identified have putative TCF binding sites, and we show that the TCF binding
site is required for induction of Follistatin. Several of the target genes have
a cooperative response to a combination of Wnt and BMP. CONCLUSIONS: Wnt
signaling activates genes that promote stem cell fate and inhibit cellular
differentiation and regulates a remarkable number of genes involved in its own
signaling system.

PMID: 12095419 [PubMed - indexed for MEDLINE]


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