PUBLICATION

Knockdown of duplicated zebrafish hoxb1 genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention

Authors
McClintock, J.M., Kheirbek, M.A., and Prince, V.E.
ID
ZDB-PUB-020514-10
Date
2002
Source
Development (Cambridge, England)   129(10): 2339-2354 (Journal)
Registered Authors
McClintock, James, Prince, Victoria E.
Keywords
zebrafish; Hox; hindbrain; rhombomere; branchiomotor neurons; reticulospinal neurons; morpholino; sub-functionalization; DDC model
MeSH Terms
  • Animals
  • Body Patterning/genetics
  • Cranial Nerves/embryology
  • Down-Regulation
  • Embryo, Nonmammalian
  • Female
  • Gene Duplication
  • Gene Expression Regulation, Developmental
  • Genetic Techniques
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Mutation
  • Neurons/physiology
  • Regulatory Sequences, Nucleic Acid
  • Rhombencephalon/embryology*
  • Transcription, Genetic
  • Zebrafish/embryology
  • Zebrafish/genetics*
PubMed
11973267 Full text @ Development
Abstract
We have used a morpholino-based knockdown approach to investigate the functions of a pair of zebrafish Hox gene duplicates, hoxb1a and hoxb1b, which are expressed during development of the hindbrain. We find that the zebrafish hoxb1 duplicates have equivalent functions to mouse Hoxb1 and its paralogue Hoxa1. Thus, we have revealed a 'function shuffling' among genes of paralogue group 1 during the evolution of vertebrates. Like mouse Hoxb1, zebrafish hoxb1a is required for migration of the VIIth cranial nerve branchiomotor neurons from their point of origin in hindbrain rhombomere 4 towards the posterior. By contrast, zebrafish hoxb1b, like mouse Hoxa1, is required for proper segmental organization of rhombomere 4 and the posterior hindbrain. Double knockdown experiments demonstrate that the zebrafish hoxb1 duplicates have partially redundant functions. However, using an RNA rescue approach, we reveal that these duplicated genes do not have interchangeable biochemical functions: only hoxb1a can properly pattern the VIIth cranial nerve. Despite this difference in protein function, we provide evidence that the hoxb1 duplicate genes were initially maintained in the genome because of complementary degenerative mutations in defined cis-regulatory elements.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping