1: Development. 2005 Jul;132(14):3243-53. 

Hedgehog signaling controls dorsoventral patterning, blastema cell proliferation
and cartilage induction during axolotl tail regeneration.

Schnapp E, Kragl M, Rubin L, Tanaka EM.

Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse
108, 01307 Dresden, Germany.

Tail regeneration in urodeles requires the coordinated growth and patterning of
the regenerating tissues types, including the spinal cord, cartilage and muscle.
The dorsoventral (DV) orientation of the spinal cord at the amputation plane
determines the DV patterning of the regenerating spinal cord as well as the
patterning of surrounding tissues such as cartilage. We investigated this
phenomenon on a molecular level. Both the mature and regenerating axolotl spinal
cord express molecular markers of DV progenitor cell domains found during
embryonic neural tube development, including Pax6, Pax7 and Msx1. Furthermore,
the expression of Sonic hedgehog (Shh) is localized to the ventral floor plate
domain in both mature and regenerating spinal cord. Patched1 receptor expression
indicated that hedgehog signaling occurs not only within the spinal cord but is
also transmitted to the surrounding blastema. Cyclopamine treatment revealed
that hedgehog signaling is not only required for DV patterning of the
regenerating spinal cord but also had profound effects on the regeneration of
surrounding, mesodermal tissues. Proliferation of tail blastema cells was
severely impaired, resulting in an overall cessation of tail regeneration, and
blastema cells no longer expressed the early cartilage marker Sox9. Spinal cord
removal experiments revealed that hedgehog signaling, while required for
blastema growth is not sufficient for tail regeneration in the absence of the
spinal cord. By contrast to the cyclopamine effect on tail regeneration,
cyclopamine-treated regenerating limbs achieve a normal length and contain
cartilage. This study represents the first molecular localization of DV
patterning information in mature tissue that controls regeneration.
Interestingly, although tail regeneration does not occur through the formation
of somites, the Shh-dependent pathways that control embryonic somite patterning
and proliferation may be utilized within the blastema, albeit with a different
topography to mediate growth and patterning of tail tissues during regeneration.

PMID: 15983402 [PubMed - indexed for MEDLINE]


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2: Development. 2004 Nov;131(21):5327-39. Epub 2004 Sep 29. 

Canonical Wnt activity regulates trunk neural crest delamination linking
BMP/noggin signaling with G1/S transition.

Burstyn-Cohen T, Stanleigh J, Sela-Donenfeld D, Kalcheim C.

Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical
School, PO Box 12272, Jerusalem 91120, Israel.

Delamination of premigratory neural crest cells depends on a balance between
BMP/noggin and on successful G1/S transition. Here, we report that BMP regulates
G1/S transition and consequent crest delamination through canonical Wnt
signaling. Noggin overexpression inhibits G1/S transition and blocking G1/S
abrogates BMP-induced delamination; moreover, transcription of Wnt1 is
stimulated by BMP and by the developing somites, which concomitantly inhibit
noggin production. Interfering with beta-catenin and LEF/TCF inhibits G1/S
transition, neural crest delamination and transcription of various BMP-dependent
genes, which include Cad6B, Pax3 and Msx1, but not that of Slug, Sox9 or FoxD3.
Hence, we propose that developing somites inhibit noggin transcription in the
dorsal tube, resulting in activation of BMP and consequent Wnt1 production.
Canonical Wnt signaling in turn stimulates G1/S transition and generation of
neural crest cell motility independently of its proposed role in earlier neural
crest specification.

PMID: 15456730 [PubMed - indexed for MEDLINE]


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