ZFIN ID: ZDB-PUB-120510-6
The zebrafish sf3b1(b460) mutant reveals differential requirements for the sf3b1 pre-mRNA processing gene during neural crest development
An, M., and Henion, P.D.
Date: 2012
Source: The International journal of developmental biology   56(4): 223-237 (Journal)
Registered Authors: An, Min, Henion, Paul
Keywords: neural crest, pre-mRNA, splicing, zebrafish
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Base Sequence
  • Blotting, Western
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental
  • Immunohistochemistry
  • In Situ Hybridization
  • Melanophores/cytology
  • Melanophores/metabolism
  • Molecular Sequence Data
  • Mutation*
  • Neural Crest/cytology
  • Neural Crest/embryology
  • Neural Crest/metabolism*
  • RNA Precursors/genetics*
  • RNA Precursors/metabolism
  • RNA Splice Sites/genetics
  • RNA Splicing
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 22562198 Full text @ Int. J. Dev. Biol.

The functions of gene regulatory networks that control embryonic cell diversification occur on a background of constitutively active molecular machinery necessary for the elaboration of genetic interactions. The essential roles of subsets of such “housekeeping” genes in the regulation of specific aspects of development have become increasingly clear. Pre-mRNA processing is essential for production of functional transcripts by, for example, excision of introns. We have cloned the zebrafish toastb460 locus and found that it encodes splicing factor 3b, subunit 1 (sf3b1). The sf3b1b460 mutation causes aberrant splicing of sf3b1 resulting in functional and predicted non-functional transcripts and a 90% reduction in full-length Sf3b1 protein. The sf3b1b460 mutation was isolated in a mutagenesis screen based on the absence of neural crest-derived melanophores. Further analysis revealed specific earlier defects in neural crest development, whereas the early development of other ectodermal populations appears unaffected. The expression of essential transcriptional regulators of neural crest development are severely disrupted in sf3b1b460 mutants, due in part to defects in pre-mRNA processing of a subset of these factors, leading to defects in neural crest sublineage specification, survival and migration. Misexpression of a subset of these factors rescues aspects of neural crest development in mutant embryos. Our results indicate that although sf3b1 is a ubiquitously essential gene, the degree to which it is required exhibits tissue-type specificity during early embryogenesis. Further, the developmental defects caused by the sf3b1b460 mutation provide insights into genetic interactions among members of the gene regulatory network controlling neural crest development.