The origin of the parathyroid gland

Okabe, M., and Graham, A.
Proceedings of the National Academy of Sciences of the United States of America   101(51): 17716-17719 (Journal)
Registered Authors
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Biological Evolution*
  • Chick Embryo
  • DNA-Binding Proteins
  • Dogfish/embryology
  • Dogfish/genetics
  • Dogfish/metabolism
  • Gills/embryology
  • Gills/metabolism
  • Gnathostoma/embryology
  • Gnathostoma/genetics
  • Gnathostoma/metabolism
  • Humans
  • Molecular Sequence Data
  • Neuropeptides/genetics
  • Neuropeptides/metabolism*
  • Organ Specificity
  • Parathyroid Glands/embryology*
  • Parathyroid Glands/metabolism*
  • Parathyroid Hormone/chemistry
  • Parathyroid Hormone/genetics
  • Pharynx/embryology
  • Pharynx/metabolism
  • Phylogeny
  • Sequence Alignment
  • Trans-Activators/genetics
  • Trans-Activators/metabolism*
  • Transcription Factors
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins
15591343 Full text @ Proc. Natl. Acad. Sci. USA
It has long been held that the parathyroid glands and parathyroid hormone evolved with the emergence of the tetrapods, reflecting a need for new controls on calcium homeostasis in terrestrial, rather than aquatic, environments. Developmentally, the parathyroid gland is derived from the pharyngeal pouch endoderm, and studies in mice have shown that its formation is under the control of a key regulatory gene, Gcm-2. We have used a phylogenetic analysis of Gcm-2 to probe the evolutionary origins of the parathyroid gland. We show that in chicks, as in mice, Gcm-2 is expressed in the pharyngeal pouches and the forming parathyroid gland. We find that Gcm-2 is present not only in tetrapods but also in teleosts and chondrichthyans, and that in these species, Gcm-2 is expressed within the pharyngeal pouches and internal gill buds that derive from them in zebrafish (Danio rerio), a teleost, and dogfish (Scyliorhinus canicula), a chondrichthyan. We further demonstrate that Gcm-2 is required for the formation of the internal gill buds in zebrafish. We also have identified parathyroid hormone 1/2-encoding genes in fish and show that these genes are expressed by the gills. We further show that the gills express the calcium-sensing receptor, which is used in tetrapods to monitor serum calcium levels. These results indicate that the tetrapod parathyroid gland and the gills of fish are evolutionarily related structures, and that the parathyroid likely came into being as a result of the transformation of the gills during tetrapod evolution.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes