Pitx2 regulates gonad morphogenesis

  1. Joaquín Rodríguez-León*,
  2. Concepción Rodríguez Esteban,
  3. Mercè Martí*,
  4. Belén Santiago-Josefat*,
  5. Ilir Dubova*,,
  6. Xavier Rubiralta*,, and
  7. Juan Carlos Izpisúa Belmonte*,,
  1. *Center of Regenerative Medicine in Barcelona, Doctor Aiguader 88, 08003 Barcelona, Spain; and
  2. Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037
  1. Communicated by Clifford J. Tabin, Harvard Medical School, Boston, MA, May 21, 2008 (received for review February 5, 2008)

Abstract

Organ shape and size, and, ultimately, organ function, relate in part to the cell and tissue spatial arrangement that takes place during embryonic development. Despite great advances in the genetic regulatory networks responsible for tissue and organ development, it is not yet clearly understood how specific gene functions are linked to the specific morphogenetic processes underlying the internal organ asymmetries found in vertebrate animals. During female chick embryogenesis, and in contrast to males where both testes develop symmetrically, asymmetrical gonad morphogenesis results in only one functional ovary. The disposition of paired organs along the left–right body axis has been shown to be regulated by the activity of the homeobox containing gene pitx2. We have found that pitx2 regulates cell adhesion, affinity, and cell recognition events in the developing gonad primordium epithelia. This in turn not only allows for proper somatic development of the gonad cortex but also permits the proliferation and differentiation of primordial germ cells. We illustrate how Pitx2 activity directs asymmetrical gonad morphogenesis by controlling mitotic spindle orientation of the developing gonad cortex and how, by modulating cyclinD1 expression during asymmetric ovarian development, Pitx2 appears to control gonad organ size. All together our observations indicate that the effects elicited by Pitx2 during the development of the female chick ovary are critical for cell topology, growth, fate, and ultimately organ morphogenesis and function.

Footnotes

  • To whom correspondence should be addressed. E-mail: belmonte{at}salk.edu
  • Author contributions: J.R.-L. and C.R.E. contributed equally to this work; J.R.-L., C.R.E., and J.C.I.B. designed research; J.R.-L., C.R.E., M.M., B.S.-J., I.D., and X.R. performed research; J.R.-L., C.R.E., M.M., B.S.-J., I.D., and X.R. contributed new reagents/analytic tools; J.R.-L., C.R.E., M.M., B.S.-J., I.D., X.R., and J.C.I.B. analyzed data; and J.R.-L., C.R.E., and J.C.I.B. wrote the paper.

  • The authors declare no conflict of interest.

  • This article contains supporting information online at www.pnas.org/cgi/content/full/0804904105/DCSupplemental.

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