PUBLICATION

Hedgehog signalling is required for cloacal development in the zebrafish embryo

Authors
Parkin, C.A., Allen, C.E., and Ingham, P.W.
ID
ZDB-PUB-090106-43
Date
2009
Source
The International journal of developmental biology   53(1): 45-57 (Journal)
Registered Authors
Allen, Claire, Ingham, Philip, Parkin, Caroline
Keywords
zebrafish, sonic hedgehog, gut, anorectal malformations, cloaca, stenosis, Adriamycin
MeSH Terms
  • Signal Transduction*/drug effects
  • Hedgehog Proteins/genetics
  • Hedgehog Proteins/metabolism*
  • Veratrum Alkaloids/pharmacology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Gene Expression Regulation, Developmental
  • Cloaca/cytology
  • Cloaca/embryology*
  • Cloaca/metabolism*
  • Mutation/genetics
  • Apoptosis
  • Animals
  • Animals, Genetically Modified
  • Transcription Factors/genetics
  • Transcription Factors/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
(all 19)
PubMed
19123126 Full text @ Int. J. Dev. Biol.
Abstract
The Hedgehog (Hh) family of signalling molecules is essential for a wide range of developmental processes. Mammalian studies have implicated the Hedgehog pathway in the aetiology of anorectal malformations (ARMs), relatively common congenital anomalies caused by failures in the development of the cloaca. In this study we demonstrate that Hh signalling is absolutely required for the formation of the zebrafish cloaca and that the severity of the posterior gut abnormalities induced by a reduction in Hh activity is dependent on the levels of Hh signal transduction. The complete loss of all Hh activity results in the most severe defects and the critical period for Hh activity is between 34 and 74 hours post fertilisation. Using a range of mutant genotypes that cause notochord and floorplate abnormalities, we show that the source of the Hh signals required for posterior gut formation is the endoderm and not the notochord, as previously postulated in mammalian models of ARMs. We show that Adriamycin, a drug known to cause ARMs in rat, but not chick embryos, has no effect on the development of the zebrafish gastrointestinal tract. These studies establish the zebrafish as a model for ARMs, and for the elucidation of other pathways involved in hindgut developmental processes.
Genes / Markers
Figures
Figure Gallery (8 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b104
    Indel
    b577
      Point Mutation
      b641
        Point Mutation
        ctd_unspecified
          Unspecified
          doc_unspecified
            Unspecified
            hu2131
              Point Mutation
              lama1_unspecified
                Unspecified
                lamc1_unspecified
                  Unspecified
                  noto_unspecified
                    Unspecified
                    t4
                      Deficiency
                      1 - 10 of 15
                      Show
                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      Antibodies
                      No data available
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      No data available
                      Mapping
                      No data available