Genetic analysis of the two zebrafish patched homologues identifies novel roles for the hedgehog signaling pathway
| Autor: | Fredericus J.M. van Eeden, Marjo J. den Broeder, Evelyn Groot, Marco J. Koudijs |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Patched Receptors
Patched Embryo Nonmammalian DNA Mutational Analysis Molecular Sequence Data Receptors Cell Surface Tretinoin Biology 03 medical and health sciences 0302 clinical medicine GLI1 GLI3 Animals Hedgehog Proteins Eye Abnormalities Hedgehog Zebrafish lcsh:QH301-705.5 Body Patterning 030304 developmental biology Genetics 0303 health sciences Base Sequence Sequence Homology Amino Acid Veratrum Alkaloids Animal Structures Gene Expression Regulation Developmental Membrane Proteins Zebrafish Proteins biology.organism_classification Hedgehog signaling pathway Patched-1 Receptor Phenotype Somites lcsh:Biology (General) Mutation biology.protein Mutant Proteins RNA Splice Sites 030217 neurology & neurosurgery Research Article Signal Transduction Genetic screen Developmental Biology |
| Zdroj: | BMC Developmental Biology, 8. BioMed Central BMC Developmental Biology, Vol 8, Iss 1, p 15 (2008) BMC Developmental Biology |
| ISSN: | 1471-213X |
| Popis: | BackgroundAberrant activation of the Hedgehog (Hh) signaling pathway in different organisms has shown the importance of this family of morphogens during development. Genetic screens in zebrafish have assigned specific roles for Hh in proliferation, differentiation and patterning, but mainly as a result of a loss of its activity. We attempted to fully activate the Hh pathway by removing both receptors for the Hh proteins, called Patched1 and 2, which are functioning as negative regulators in this pathway.ResultsHere we describe a splice-donor mutation in Ptc1, calledptc1hu1602, which in a homozygous state results in a subtle eye and somite phenotype. Since we recently positionally cloned aptc2mutant, aptc1;ptc2double mutant was generated, showing severely increased levels ofptc1,gli1andnkx2.2a, confirming an aberrant activation of Hh signaling. As a consequence, a number of phenotypes were observed that have not been reported previously usingShhmRNA overexpression. Somites ofptc1;ptc2double mutants do not express anteroposterior polarity markers, however initial segmentation of the somites itself is not affected. This is the first evidence that segmentation and anterior/posterior (A/P) patterning of the somites are genetically uncoupled processes. Furthermore, a novel negative function of Hh signaling is observed in the induction of the fin field, acting well before any of the previously reported function of Shh in fin formation and in a way that is different from the proposed early role of Gli3 in limb/fin bud patterning.ConclusionThe generation and characterization of theptc1;ptc2double mutant assigned novel and unexpected functions to the Hh signaling pathway. Additionally, these mutants will provide a useful system to further investigate the consequences of constitutively activated Hh signaling during vertebrate development. |
| Databáze: | OpenAIRE |
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