OR39-5 -catenin is Required in the Neural Crest and Mesencephalon for Pituitary Organogenesis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR39-Pituitary
Basic
Monday, June 17, 2013: 11:15 AM-12:45 PM
Presentation Start Time: 12:15 PM
Room 133 (Moscone Center)
Shannon William Davis*1, Amanda Helen Mortensen2, Tatiana Fiordelisio3, Patrice E Mollard4 and Sally Ann Camper5
1University of South Carolina, Columbia, SC, 2Univ of Michigan, Ann Arbor, MI, 3Universidad Nacional Autonoma Me, DF, Coyoacan, Mexico, 4CNRS - INSERM, Montpellier, France, 5University of Michigan, Ann Arbor, MI
The pituitary gland develops from an interaction between the ventral diencephalon and the oral ectoderm that produces Rathke’s pouch, the pituitary gland precursor. Rathke’s pouch is surrounded by mesenchyme, a tissue whose influence on the pituitary gland is poorly defined.  We have determined that the mesenchyme rostral to Rathke’s pouch is derived from the neural crest.  The mesenchyme caudal to the pituitary must originate from definitive mesoderm; therefore, the mesenchyme surrounding the pituitary has multiple origins.  In order to determine the influence of the neural crest derived mesenchyme on pituitary development, we examined two mouse models that affect neural crest function specifically.  The neural crest lineage requires β-catenin for cell survival during cell migration and for normal craniofacial development, but the affect on pituitary development was not investigated (1).  We used the Wnt1cre and P0cre lines to generate conditional β-catenin loss-of-function genotypes and observed two different pituitary phenotypes.   The Wnt1cre causes an expansion of Rathke’s pouch.  This is associated with an increase in Bmp and Fgf signaling from the organizing center in the ventral diencephalon that induces Rathke’s pouch formation.  This phenotype is not observed in the P0cre; therefore, it is unlikely to result from loss of β-catenin in the neural crest.  Wnt1cre is also expressed in the mesencephalon, where β-catenin is instrumental in neural tube patterning.  This supports the hypothesis that the pituitary organizing center is regulated by Wnt signaling in the mesencephalon. When β-catenin is deleted from the neural crest using either the Wnt1cre or the P0cre, the vasculature within the pituitary becomes dysmorphic. Thus, we have established that the neural crest contributes to pituitary vascular development and that β-catenin is required in the Wnt1 expression domain for establishing the organizing center that induces Rathke’s pouch.

(1) Brault, V., et al.,  Development, 2001;128:1253

Nothing to Disclose: SWD, AHM, TF, PEM, SAC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: NIH Grant R3730428 awarded to SAC