Andoniadou, CL

Gaston-Massuet, C

Martinez-Barbera, JP

English

UCL Discovery

13-P115Hesx1 antagonises canonical Wnt signalling in anterior forebrainand pituitary glandCynthia L. Andoniadou, Carles Gaston-Massuet, Juan PedroMartinez-BarberaNeural Development Unit, UCL Institute of Child Health, London, UnitedKingdomWe have previously shown that the activity of the homeoboxtranscription factor Hesx1 is required to specify correct forebraindevelopment, possibly through antagonizing canonical Wnt sig-nalling, thus maintaining anterior identity in mouse. Hesx1mutants exhibit anterior forebrain truncations of variable severityand in the more sensitive pituitary gland, defects resulting fromtheover-proliferationofprecursors.MutationsinHESX1havebeenidentiﬁed in patients with hypopituitarism. Our data suggest thatthe expression of Hesx1 between 9.5 and 13.5 dpc in the pituitaryis crucial to antagonize Wnt signalling in order to temporally regu-late proliferation. We have performed conditional gain and loss offunction of b-catenin experiments in the Hesx1 domain, demon-stratingthatup-regulation ofcanonical Wntsignalling affects pro-S229 MECHANISMS OF DEVELOPMENT 126 (2009) S195–S238liferation and terminal differentiation of the Pit1-lineage in thedeveloping gland, leading to an embryonic phenotype similar tothat of loss of Hesx1 and dwarﬁsm in surviving animals. On theother hand, a conditional reduction in Wnt signalling is not sufﬁ-cient to rescue Hesx1 mutant pituitary defects however results ina marked improvement of the forebrain defects, conﬁrming therole of Hesx1 as a canonical Wnt signalling antagonist.doi:10.1016/j.mod.2009.06.588S230 MECHANISMS OF DEVELOPMENT 126 (2009) S195–S238

Hesx1 antagonises canonical Wnt signalling in anterior forebrain and pituitary gland

Abstract

Similar works

Full text

Available Versions

UCL Discovery