PUBLICATION
lessen encodes a zebrafish trap100 required for enteric nervous system development
- Authors
- Pietsch, J., Delalande, J.M., Jakaitis, B., Stensby, J.D., Dohle, S., Talbot, W.S., Raible, D.W., and Shepherd, I.T.
- ID
- ZDB-PUB-060124-1
- Date
- 2006
- Source
- Development (Cambridge, England) 133(3): 395-406 (Journal)
- Registered Authors
- Raible, David, Shepherd, Iain T., Talbot, William S.
- Keywords
- Neural crest, Zebrafish, Craniofacial, ENS development, lessen (lsn), trap100 (thrap4), Proliferation
- MeSH Terms
-
- Animals
- Body Patterning*
- Cell Movement
- Cloning, Molecular
- Endoderm/physiology
- Enteric Nervous System/embryology*
- Enteric Nervous System/physiology
- Facial Bones/anatomy & histology
- Facial Bones/embryology
- Female
- Gene Expression Regulation, Developmental
- Humans
- In Situ Hybridization
- Male
- Mutation
- Neural Crest/cytology
- Neural Crest/physiology
- Oligonucleotides, Antisense/genetics
- Oligonucleotides, Antisense/metabolism
- Phenotype
- Skull/anatomy & histology
- Skull/embryology
- Thymus Gland/anatomy & histology
- Thymus Gland/embryology
- Trans-Activators/genetics*
- Trans-Activators/metabolism*
- Transcription Factors/genetics*
- Transcription Factors/metabolism*
- Zebrafish/anatomy & histology
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism*
- PubMed
- 16396911 Full text @ Development
Citation
Pietsch, J., Delalande, J.M., Jakaitis, B., Stensby, J.D., Dohle, S., Talbot, W.S., Raible, D.W., and Shepherd, I.T. (2006) lessen encodes a zebrafish trap100 required for enteric nervous system development. Development (Cambridge, England). 133(3):395-406.
Abstract
The zebrafish enteric nervous system (ENS), like those of all other vertebrate species, is principally derived from the vagal neural crest. The developmental controls that govern the specification and patterning of the ENS are not well understood. To identify genes required for the formation of the vertebrate ENS, we preformed a genetic screen in zebrafish. We isolated the lessen (lsn) mutation that has a significant reduction in the number of ENS neurons as well as defects in other cranial neural crest derived structures. We show that the lsn gene encodes a zebrafish orthologue of Trap100, one of the subunits of the TRAP/mediator transcriptional regulation complex. A point mutation in trap100 causes a premature stop codon that truncates the protein, causing a loss of function. Antisense-mediated knockdown of trap100 causes an identical phenotype to lsn. During development trap100 is expressed in a dynamic tissue-specific expression pattern consistent with its function in ENS and jaw cartilage development. Analysis of neural crest markers revealed that the initial specification and migration of the neural crest is unaffected in lsn mutants. Phosphohistone H3 immunocytochemistry revealed that there is a significant reduction in proliferation of ENS precursors in lsn mutants. Using cell transplantation studies, we demonstrate that lsn/trap100 acts cell autonomously in the pharyngeal mesendoderm and influences the development of neural crest derived cartilages secondarily. Furthermore, we show that endoderm is essential for ENS development. These studies demonstrate that lsn/trap100 is not required for initial steps of cranial neural crest development and migration, but is essential for later proliferation of ENS precursors in the intestine.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping