PUBLICATION
Apc1 is required for maintenance of local brain organizers and dorsal midbrain survival
- Authors
- Paridaen, J.T., Danesin, C., Elas, A.T., van de Water, S., Houart, C., and Zivkovic, D.
- ID
- ZDB-PUB-090429-13
- Date
- 2009
- Source
- Developmental Biology 331(2): 101-112 (Journal)
- Registered Authors
- Danesin, Cathy, Houart, Corinne
- Keywords
- none
- MeSH Terms
-
- Animals
- Body Patterning/physiology
- Brain/abnormalities
- Brain/embryology*
- Brain/metabolism
- Embryo, Nonmammalian/metabolism
- Fibroblast Growth Factors/metabolism
- Mesencephalon/abnormalities
- Mesencephalon/embryology
- Mesencephalon/metabolism
- Mutation
- Organizers, Embryonic/physiology*
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/metabolism*
- Wnt Proteins/physiology
- Zebrafish/embryology*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- beta Catenin/genetics
- beta Catenin/metabolism
- PubMed
- 19397905 Full text @ Dev. Biol.
Citation
Paridaen, J.T., Danesin, C., Elas, A.T., van de Water, S., Houart, C., and Zivkovic, D. (2009) Apc1 is required for maintenance of local brain organizers and dorsal midbrain survival. Developmental Biology. 331(2):101-112.
Abstract
The tumor suppressor Apc1 is an intracellular antagonist of the Wnt/beta-catenin pathway, which is vital for induction and patterning of the early vertebrate brain. However, its role in later brain development is less clear. Here, we examined the mechanisms underlying effects of an Apc1 zygotic-effect mutation on late brain development in zebrafish. Apc1 is required for maintenance of established brain subdivisions and control of local organizers such as the isthmic organizer (IsO). Caudal expansion of Fgf8 from IsO into the cerebellum is accompanied by hyperproliferation and abnormal cerebellar morphogenesis. Loss of apc1 results in reduced proliferation and apoptosis in the dorsal midbrain. Mosaic analysis shows that Apc is required cell-autonomously for maintenance of dorsal midbrain cell fate. The tectal phenotype occurs independently of Fgf8-mediated IsO function and is predominantly caused by stabilization of beta-catenin and subsequent hyperactivation of Wnt/beta-catenin signaling, which is mainly mediated through LEF1 activity. Chemical activation of the Wnt/beta-catenin in wild-type embryos during late brain maintenance stages phenocopies the IsO and tectal phenotypes of the apc mutants. These data demonstrate that Apc1-mediated restriction of Wnt/beta-catenin signaling is required for maintenance of local organizers and tectal integrity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping