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: Curr Opin Genet Dev. 1996 Jun;6(3):334-42. 

Transcription factors in disease.

Engelkamp D, van Heyningen V.

MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
dieter@hgu.mrc.ac.uk

Mutations affecting several predominantly tissue-specific transcriptional
regulators have recently been associated with disease phenotypes. Although the
mutational spectrum is variable, many of the reported cases involve clear
loss-of-function mutations-such as Waardenburg syndrome type 1, aniridia and
Rubinstein-Taybi syndrome-suggesting that the genetic mechanism involved in
disease is haplo-insufficiency. The high degree of dosage sensitivity often
appears to affect only a subset of the tissues that express the gene. Position
effects with cytogenetic rearrangements well outside the coding region have been
implicated for four of the genes discussed: POU3F4, SOX9, PAX6, and GL13.

Publication Types:
    Review
    Review, Tutorial

PMID: 8791518 [PubMed - indexed for MEDLINE]


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