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ZFIN ID: ZDB-PUB-090518-24
Targeted Gene Knockdown in Zebrafish Reveals Distinct Intraembryonic Functions for Insulin-Like Growth Factor II Signaling
White, Y.A., Kyle, J.T., and Wood, A.W.
Date: 2009
Source: Endocrinology   150(9): 4366-4375 (Journal)
Registered Authors: Wood, Antony W.
Keywords: midline, notochord, organizer, kidney, embryo
MeSH Terms:
  • Animals
  • Embryo, Nonmammalian/metabolism*
  • Gene Expression Regulation, Developmental*
  • Insulin-Like Growth Factor II/genetics
  • Insulin-Like Growth Factor II/physiology*
  • Signal Transduction/physiology*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Zebrafish Proteins/physiology*
PubMed: 19443571 Full text @ Endocrinology
Insulin-like growth factor 2 (IGF-II) is the predominant IGF ligand regulating prenatal growth in all vertebrates, including humans, but its central role in placental development has confounded efforts to fully elucidate its functions within the embryo. Here, we use a non-placental model vertebrate (zebrafish) to interrogate the intraembryonic functions of IGF-II signaling. The zebrafish genome contains two co-orthologs of mammalian IGF2 (igf2a, igf2b), which exhibit distinct patterns of expression during embryogenesis. Expression of igf2a mRNA is restricted to the notochord, primarily during segmentation/neurulation. By contrast, igf2b mRNA is expressed in midline tissues adjacent to the notochord, with additional sites of expression in the ventral forebrain, and the pronephros. To identify their intraembryonic functions, we suppressed the expression of each gene with morpholino oligonucleotides. Knockdown of igf2a led to defects in dorsal midline development, characterized by delayed segmentation, notochord undulations, and ventral curvature. Similarly, suppression of igf2b led to defects in dorsal midline development, but also induced ectopic fusion of the nephron primordia, and defects in ventral forebrain development. Subsequent onset of severe body edema in igf2b, but not igf2a morphants, further suggested a distinct role for igf2b in development of the embryonic kidney. Simultaneous knockdown of both genes increased the severity of dorsal midline defects, confirming a conserved role for both genes in dorsal midline development. Collectively, these data provide evidence that the zebrafish orthologs of IGF2 function in dorsal midline development during segmentation/neurulation, while one paralog, igf2b, has evolved additional, distinct functions during subsequent organogenesis.