TY  - JOUR
SN  - 0950-1991
UR  - http://doi.org/10.1242/dev.153387
JF  - Development
A1  - Martinez-Barbera, JP
SP  - 3289
VL  - 144
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
IS  - 18
ID  - discovery1571051
N2  - Sonic hedgehog (SHH) is an essential morphogenetic signal dictating cell fate decisions in several developing organs in mammals. In vitro data suggest that SHH is required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, in vivo studies have failed to reveal such a function, supporting instead, a critical role for SHH in promoting proliferation of these RP progenitors and for differentiation of pituitary cell types. Here, we have used a genetic approach to demonstrate that activation of the SHH pathway is necessary to induce LHX3+/LHX4+ RP identity in mouse embryos. First, we show that conditional deletion of Shh in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of RP development, with lack of Lhx3/Lhx4 expression in RP epithelium at 9.0 dpc (days post coitum) and total loss of pituitary tissue by 12.5 dpc. Conversely, over-activation of the SHH pathway by conditional deletion of Ptch1 in RP progenitors leads to severe hyperplasia and enlargement of the Sox2+ve stem cell compartment by the end of gestation.
KW  - Pituitary
KW  -  Mouse
KW  -  Sonic hedgehog
KW  -  Patched
TI  - Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors
EP  - 3302
AV  - public
Y1  - 2017/09/15/
ER  -