Isolation and characterization of a chicken homolog of the c-ret proto-oncogene

A. Schuchardt, S. Srinivas, V. Pachnis, F. Costantini

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The c-ret proto-oncogene encodes a receptor tyrosine kinase that plays important roles in human disease and in normal mammalian development. Mutations in the human RET gene are associated with multiple endocrine neoplasia syndromes and Hirschsprung's disease in humans, while targeted mutagenesis of murine c-ret resulted in severe developmental abnormalities affecting the excretory and peripheral nervous systems. To examine the evolutionary conservation of the ret protein sequence and its developmental expression pattern, we isolated and sequenced cDNA clones of chicken c-ret and examined its expression in chick embryos and adult tissues. The cytoplasmic domains of chicken and human ret were relatively well conserved (91% similar), but the extracellular domains were more divergent (68% similar), although the conservation of cysteine residues in this region suggests a conserved secondary structure. As in mouse and human, chicken c-ret encodes two protein isoforms. The number and sizes of the transcripts were similar to those in human and mouse cells, and during chick embryogenesis, c-ret mRNA was observed in many of the same sites as in the mouse, including the Wolffian duct and ureteric bud, the enteric, dorsal root, sympathetic and facioacoustic ganglia, and the ventral spinal cord. Evolutionary differences in expression were observed in the trigeminal ganglion, the ventral roots of the spinal cord, the mesenchymal cells of the branchial arches and the adult testes. The results are discussed with regard to the role of the ret receptor in normal development and disease.

Original languageEnglish (US)
Pages (from-to)641-649
Number of pages9
JournalOncogene
Volume10
Issue number4
StatePublished - Jan 1 1995

Fingerprint

Proto-Oncogenes
Chickens
Spinal Nerve Roots
Spinal Cord
Wolffian Ducts
Multiple Endocrine Neoplasia
Branchial Region
Trigeminal Ganglion
Hirschsprung Disease
Sympathetic Ganglia
Peripheral Nervous System
Receptor Protein-Tyrosine Kinases
Chick Embryo
Mutagenesis
Embryonic Development
Cysteine
Testis
Protein Isoforms
Complementary DNA
Clone Cells

Keywords

  • Embryogenesis
  • Evolution
  • Hirschsprung's disease
  • Nervous system
  • Proto-oncogene
  • Receptor tyrosine kinase
  • RET

Cite this

Schuchardt, A., Srinivas, S., Pachnis, V., & Costantini, F. (1995). Isolation and characterization of a chicken homolog of the c-ret proto-oncogene. Oncogene, 10(4), 641-649.

Isolation and characterization of a chicken homolog of the c-ret proto-oncogene. / Schuchardt, A.; Srinivas, S.; Pachnis, V.; Costantini, F.

In: Oncogene, Vol. 10, No. 4, 01.01.1995, p. 641-649.

Research output: Contribution to journalArticle

Schuchardt, A, Srinivas, S, Pachnis, V & Costantini, F 1995, 'Isolation and characterization of a chicken homolog of the c-ret proto-oncogene', Oncogene, vol. 10, no. 4, pp. 641-649.
Schuchardt A, Srinivas S, Pachnis V, Costantini F. Isolation and characterization of a chicken homolog of the c-ret proto-oncogene. Oncogene. 1995 Jan 1;10(4):641-649.
Schuchardt, A. ; Srinivas, S. ; Pachnis, V. ; Costantini, F. / Isolation and characterization of a chicken homolog of the c-ret proto-oncogene. In: Oncogene. 1995 ; Vol. 10, No. 4. pp. 641-649.
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