4.7 Review

Pitx genes in development and disease

Journal

CELLULAR AND MOLECULAR LIFE SCIENCES
Volume 78, Issue 11, Pages 4921-4938

Publisher

SPRINGER BASEL AG
DOI: 10.1007/s00018-021-03833-7

Keywords

Development; Evolution; Disease; Homeobox genes; Pitx

Funding

  1. College of Pharmacy at the Oregon State University

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Homeobox genes encode SSTFs that regulate organogenesis in eukaryotes, while Pitx genes, belonging to the highly conserved homeobox genes, mainly regulate LR asymmetry and organ development and symmetry. Mutations in Pitx genes can cause various congenital defects and cancers, but also have the potential to play a role in regenerative medicine.
Homeobox genes encode sequence-specific transcription factors (SSTFs) that recognize specific DNA sequences and regulate organogenesis in all eukaryotes. They are essential in specifying spatial and temporal cell identity and as a result, their mutations often cause severe developmental defects. Pitx genes belong to the PRD class of the highly evolutionary conserved homeobox genes in all animals. Vertebrates possess three Pitx paralogs, Pitx1, Pitx2, and Pitx3 while non-vertebrates have only one Pitx gene. The ancient role of regulating left-right (LR) asymmetry is conserved while new functions emerge to afford more complex body plan and functionalities. In mouse, Pitx1 regulates hindlimb tissue patterning and pituitary development. Pitx2 is essential for the development of the oral cavity and abdominal wall while regulates the formation and symmetry of other organs including pituitary, heart, gut, lung among others by controlling growth control genes upon activation of the Wnt/ss-catenin signaling pathway. Pitx3 is essential for lens development and migration and survival of the dopaminergic neurons of the substantia nigra. Pitx gene mutations are linked to various congenital defects and cancers in humans. Pitx gene family has the potential to offer a new approach in regenerative medicine and aid in identifying new drug targets.

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