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ZFIN ID: ZDB-PUB-060210-4
Rab11-FIP4 is predominantly expressed in neural tissues and involved in proliferation as well as in differentiation during zebrafish retinal development
Muto, A., Arai, K.I., and Watanabe, S.
Date: 2006
Source: Developmental Biology 292(1): 90-102 (Journal)
Registered Authors:
Keywords: Rab11-FIP4, Retina, Zebrafish, Proliferation, Differentiation
MeSH Terms:
  • Animals
  • Brain/cytology
  • Brain/embryology
  • Brain/metabolism
  • Carrier Proteins/biosynthesis*
  • Carrier Proteins/genetics
  • Carrier Proteins/physiology
  • Cell Count
  • Cell Cycle/genetics
  • Cell Cycle/physiology
  • Cell Differentiation/genetics
  • Cell Differentiation/physiology*
  • Cell Proliferation*
  • Cyclic AMP-Dependent Protein Kinases/biosynthesis
  • Cyclic AMP-Dependent Protein Kinases/genetics
  • Cyclin-Dependent Kinase Inhibitor p57/biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p57/genetics
  • Hedgehog Proteins
  • Nerve Tissue Proteins/biosynthesis*
  • Nerve Tissue Proteins/genetics
  • Nerve Tissue Proteins/physiology
  • Oligonucleotides, Antisense
  • Retina/cytology
  • Retina/embryology*
  • Retina/metabolism
  • Signal Transduction/physiology
  • Stem Cells/cytology
  • Stem Cells/metabolism
  • Trans-Activators/physiology
  • Zebrafish/embryology*
  • Zebrafish Proteins/biosynthesis*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology
  • rab GTP-Binding Proteins/biosynthesis*
  • rab GTP-Binding Proteins/genetics
  • rab GTP-Binding Proteins/physiology
PubMed: 16457799 Full text @ Dev. Biol.
Rab11 family interacting protein 4 (Rab11-FIP4) was initially identified in humans as an Rab11-binding protein, but its biological function has remained unknown. We cloned the zebrafish orthologue of Rab11-FIP4 (zRab11-FIP4) and analyzed its function in vivo by using antisense morpholino. zRab11-FIP4 was expressed as 2 alternative transcripts, i.e., the longer A-form predominantly expressed in neural tissues and the shorter B-form expressed ubiquitously; and in situ hybridization revealed that the A-form was the dominant form. In the developing retina, zRab11-FIP4 was expressed in progenitors throughout the retina at early stages; and then, along with the differentiation, the expression became gradually restricted to the ganglion cell layer and ciliary marginal zone. zRab11-FIP4A knockdown embryos exhibited eye phenotypes similar to those of the shh mutant, such as a small eye with impaired cell proliferation and the delay in cell-cycle exit and differentiation of retinal progenitors. The lack of induction of p57kip2 and enhanced expression of cyclin D1 were observed in the morphant retina. Importantly, the delay in cell-cycle exit was rescued by ectopic expression of either p57Kip2 or dominant-negative PKA, suggesting that Rab11-FIP4A plays pivotal roles in retinal development by regulating Shh signaling and a mechanism acting in parallel with Shh signaling in the control of cell-cycle exit.