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SUMMARY:Pituitary hypoplasia and decreased GnRH neurogenesis in Sox2-defic
 ient Mice - Dr. Juan Pedro Martinez-Barbera.  UCL Institute of Child Healt
 h
DTSTART:20130124T160000Z
DTEND:20130124T170000Z
UID:TALK40187@talks.cam.ac.uk
CONTACT:Annabel Griffiths
DESCRIPTION:SOX2 haploinsufficiency causes hypopituitarism in humans and s
 pecifically isolated gonadotrophin deficiency (hypogonadotrophic hypogonad
 ism\, HH). Here\, we have used a conditional approach in mice to investiga
 te the pathogenesis of these defects. First\, we demonstrate that absence 
 of SOX2 in the developing Rathke’s pouch (RP) of Hesx1Cre/+\;Sox2fl/fl e
 mbryos leads to severe anterior lobe hypoplasia with a drastic reduction o
 f POU1F1 expression and severe disruption of somatotroph and thyrotroph di
 fferentiation. In contrast\, corticotrophs\, rostral-tip POU1F1-independen
 t thyrotrophs and\, interestingly\, lactotrophs and gonadotrophs are less 
 affected. Secondly\, we show that SOX2 is required for normal proliferatio
 n of RP periluminal progenitors and its absence results in failure to yiel
 d a sufficiently large pool of precursors for all cell lineages of the ant
 erior pituitary. Accordingly\, differentiated cells derived from precursor
 s exiting cell cycle at early stages (i.e. corticotrophs\, rostral-tip thy
 rotrophs and gonadotrophs) are generated\, whilst hormone-producing cells 
 originating from late-born precursors (i.e. somatotrophs and POU1F1-depend
 ent thyrotrophs) are severely impaired. Finally\, we demonstrate that two 
 previously characterised patients with SOX2 haploinsufficiency and associa
 ted HH have a measurable response to GnRH stimulation\, suggesting that it
  is not the absence of gonadotroph differentiation\, but rather their defi
 cient hypothalamic stimulation that underlies the typical HH.
LOCATION:Hodgkin Huxley Seminar Room\, Physiology Building\, Downing Site
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