eprintid: 1571051
rev_number: 46
eprint_status: archive
userid: 608
dir: disk0/01/57/10/51
datestamp: 2017-08-23 12:08:31
lastmod: 2021-12-10 23:45:19
status_changed: 2017-08-24 09:32:13
type: article
metadata_visibility: show
creators_name: Martinez-Barbera, JP
title: Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors
ispublished: pub
divisions: UCL
divisions: B02
divisions: D13
divisions: G22
keywords: Pituitary, Mouse, Sonic hedgehog, Patched
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: 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.
date: 2017-09-15
date_type: published
official_url: http://doi.org/10.1242/dev.153387
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1414436
doi: 10.1242/dev.153387
lyricists_name: Apps, John
lyricists_name: Haston, Scott
lyricists_name: Lodge, Emily
lyricists_name: Martinez-Barbera, Juan
lyricists_name: Panousopoulos, Leonidas
lyricists_id: JAPPS40
lyricists_id: SHAST33
lyricists_id: EJLOD08
lyricists_id: JPMAR49
lyricists_id: LPANO68
actors_name: Martinez-Barbera, Juan
actors_id: JPMAR49
actors_role: owner
full_text_status: public
publication: Development
volume: 144
number: 18
pagerange: 3289-3302
issn: 0950-1991
citation:        Martinez-Barbera, JP;      (2017)    Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors.                   Development , 144  (18)   pp. 3289-3302.    10.1242/dev.153387 <https://doi.org/10.1242/dev.153387>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1571051/1/Martinez-Barbera_et%20al-Resubmission%20FINAL.pdf