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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 crucial 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\u2005days post coitum (dpc) and total loss of pituitary tissue by 12.5\u2005dpc. Conversely, overactivation of the SHH pathway by conditional deletion of Ptch1 in RP progenitors leads to severe hyperplasia and enlargement of the Sox2+ stem cell compartment by the end of gestation.<\/jats:p>","DOI":"10.1242\/dev.153387","type":"journal-article","created":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:20:10Z","timestamp":1502756410000},"page":"3289-3302","source":"Crossref","is-referenced-by-count":60,"title":["Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3\/LHX4 pituitary embryonic precursors"],"prefix":"10.1242","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5292-7276","authenticated-orcid":false,"given":"Gabriela","family":"Carreno","sequence":"first","affiliation":[{"name":"Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London 1 Developmental Biology and Cancer Programme , , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7902-482X","authenticated-orcid":false,"given":"John R.","family":"Apps","sequence":"additional","affiliation":[{"name":"Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London 1 Developmental Biology and Cancer Programme , , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J.","family":"Lodge","sequence":"additional","affiliation":[{"name":"2 Centre for Craniofacial and Regenerative Biology, King's College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Panousopoulos","sequence":"additional","affiliation":[{"name":"Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London 1 Developmental Biology and Cancer Programme , , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Haston","sequence":"additional","affiliation":[{"name":"Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London 1 Developmental Biology and Cancer Programme , , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Mario","family":"Gonzalez-Meljem","sequence":"additional","affiliation":[{"name":"Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London 1 Developmental Biology and Cancer Programme , , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Hahn","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics 3 , Tumor Genetics Group , , 37073 G\u00f6ttingen \u2008 Germany"},{"name":"University of G\u00f6ttingen 3 , Tumor Genetics Group , , 37073 G\u00f6ttingen \u2008 Germany"},{"name":", 3 , Tumor Genetics Group , , 37073 G\u00f6ttingen \u2008 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-5855","authenticated-orcid":false,"given":"Cynthia L.","family":"Andoniadou","sequence":"additional","affiliation":[{"name":"2 Centre for Craniofacial and Regenerative Biology, King's College London, London SE1 9RT, UK"},{"name":"Technische Universit\u00e4t Dresden 4 Department of Internal Medicine III , , 01307 Dresden , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Pedro","family":"Martinez-Barbera","sequence":"additional","affiliation":[{"name":"Birth Defects Research Centre, Great Ormond Street Institute of Child Health, University College London 1 Developmental Biology and Cancer Programme , , London WC1N 1EH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061215554335300_DEV153387C1","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1242\/dev.121.10.3279","article-title":"Forebrain and midbrain regions are deleted in Otx2-\/- mutants due to a defective anterior neuroectoderm specification during gastrulation","volume":"121","author":"Acampora","year":"1995","journal-title":"Development"},{"key":"2024061215554335300_DEV153387C2","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1210\/er.22.1.2","article-title":"POU domain factors in the neuroendocrine system: lessons from developmental biology provide insights into human disease","volume":"22","author":"Andersen","year":"2001","journal-title":"Endocr. 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