{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:45:42Z","timestamp":1791380742850,"version":"4.3.3"},"reference-count":40,"publisher":"The Company of Biologists","issue":"23","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Targeted disruption of the homeobox gene T\/ebp (Nkx2.1, Ttf1, Titf1) in mice results in ablation of the pituitary. Paradoxically, while T\/ebp is expressed in the ventral diencephalon during forebrain formation, it is not expressed in Rathke\u2019s pouch or in the pituitary gland at any time of embryogenesis. Examination of pituitary development in the T\/ebp homozygous null mutant embryos revealed that a pouch rudiment is initially formed but is eliminated by programmed cell death before formation of a definitive pouch. In the diencephalon of the mutant, Bmp4 expression is maintained, whereas Fgf8 expression is not detectable. These data and additional genetic and molecular observations suggest that Rathke\u2019s pouch develops in a two-step process that requires at least two sequential inductive signals from the diencephalon. First, BMP4 is required for induction and formation of the pouch rudiment, a role confirmed by analysis of Bmp4 homozygous null mutant embryos. Second, FGF8 is necessary for activation of the key regulatory gene Lhx3 and subsequent development of the pouch rudiment into a definitive pouch. This study provides firm molecular genetic evidence that morphogenesis of the pituitary primordium is induced in vivo by signals from the adjacent diencephalon.<\/jats:p>","DOI":"10.1242\/dev.125.23.4835","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T15:35:54Z","timestamp":1619192154000},"page":"4835-4840","source":"Crossref","is-referenced-by-count":277,"title":["Formation of Rathke\u2019s pouch requires dual induction from the diencephalon"],"prefix":"10.1242","volume":"125","author":[{"given":"Naoyuki","family":"Takuma","sequence":"first","affiliation":[{"name":"Laboratory of Mammalian Genes and Development 1 , National Institute of Child Health and Human Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Z.","family":"Sheng","sequence":"additional","affiliation":[{"name":"Laboratory of Mammalian Genes and Development 1 , National Institute of Child Health and Human Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhide","family":"Furuta","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 3 , Vanderbilt University Medical Center, Nashville, TN 37232-2175, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerrold M.","family":"Ward","sequence":"additional","affiliation":[{"name":"Veterinary and Tumor Pathology Section 4 , National Cancer Institute, Frederick, MD, 21702-1201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Sharma","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory 5 , The Salk Institute for Biological Studies, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigid L. M.","family":"Hogan","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute 3 , Vanderbilt University Medical Center, Nashville, TN 37232-2175, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel L.","family":"Pfaff","sequence":"additional","affiliation":[{"name":"Gene Expression Laboratory 5 , The Salk Institute for Biological Studies, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Westphal","sequence":"additional","affiliation":[{"name":"Laboratory of Mammalian Genes and Development 1 , National Institute of Child Health and Human Development"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shioko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolism 2 , National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen A.","family":"Mahon","sequence":"additional","affiliation":[{"name":"Department of Cell Biology 6 , Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1998,12,1]]},"reference":[{"key":"2023090710501678800_DEVELOP_125_23_4835C1","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1073\/pnas.92.7.2720","article-title":"P-Lim, a LIM homeodomain factor, is expressed during pituitary organ and cell commitment and synergizes with Pit-1","volume":"92","author":"Bach","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023090710501678800_DEVELOP_125_23_4835C2","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1101\/gad.11.11.1370","article-title":"A family of LIM domain-associated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins","volume":"11","author":"Bach","year":"1997","journal-title":"Genes Dev."},{"key":"2023090710501678800_DEVELOP_125_23_4835C3","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/0888-7543(90)90050-5","article-title":"The Pit-1 transcription factor is a candidate for the Snell dwarf mutation","volume":"8","author":"Camper","year":"1990","journal-title":"Genomics"},{"key":"2023090710501678800_DEVELOP_125_23_4835C4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1242\/dev.103.Supplement.101","article-title":"The fate map of the cephalic neural primordium at the presomitic to the 3-somite stage in the avian embryo","volume":"103","author":"Couly","year":"1988","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1242\/dev.121.2.439","article-title":"The mouse Fgf8 gene encodes a family of polypeptides and is expressed in regions that direct outgrowth and patterning in the developing embryo","volume":"121","author":"Crossley","year":"1995","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C6","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/0012-1606(82)90225-1","article-title":"Effect of basal diencephalon on the development of Rathke\u2019s pouch in rats: A study in combined organ culture","volume":"90","author":"Daikoku","year":"1982","journal-title":"Dev. Biol."},{"key":"2023090710501678800_DEVELOP_125_23_4835C7","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1242\/dev.125.6.1005","article-title":"Integrated FGF and BMP signaling controls the progression of progenitor cell differentiation and the emergence of pattern in the embryonic anterior pituitary","volume":"125","author":"Ericson","year":"1998","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/B978-1-4832-3229-4.50015-4","volume-title":"Neuroendocrinology","author":"Etkin","year":"1967"},{"key":"2023090710501678800_DEVELOP_125_23_4835C9","first-page":"293","article-title":"Experimental study of the factors in cytological differentiation of the adenohypophysis in the chick embryo","volume":"83","author":"Ferrand","year":"1972","journal-title":"Arch. Biol"},{"key":"2023090710501678800_DEVELOP_125_23_4835C10","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/hmg\/6.3.457","article-title":"Pituitary homeobox 2, a novel member of the bicoid-related family of homeobox genes, is a potential regulator of anterior structure formation","volume":"6","author":"Gage","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"2023090710501678800_DEVELOP_125_23_4835C11","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1242\/dev.122.1.41","article-title":"Rpx: a novel anteriorrestricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke\u2019s pouch of the mouse embryo","volume":"122","author":"Hermesz","year":"1996","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C12","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1242\/dev.111.2.531","article-title":"Involvement of bone morphogenetic protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse","volume":"111","author":"Jones","year":"1991","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C13","volume-title":"The Atlas of Mouse Development.","author":"Kaufman","year":"1992"},{"key":"2023090710501678800_DEVELOP_125_23_4835C14","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1007\/BF00318479","article-title":"Induction from posterior hypothalamus is essential for the development of the pituitary proopiomelacortin (POMC) cells of the toad (Bufo japonicus","volume":"279","author":"Kawamura","year":"1995","journal-title":"Cell Tiss. Res"},{"key":"2023090710501678800_DEVELOP_125_23_4835C15","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1101\/gad.10.1.60","article-title":"The T\/ebp null mouse: thyroidspecific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary","volume":"10","author":"Kimura","year":"1996","journal-title":"Genes Dev"},{"key":"2023090710501678800_DEVELOP_125_23_4835C16","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1440-169X.1984.00263.x","article-title":"Early development of mouse anterior pituitary: role of mesenchyme","volume":"26","author":"Kusakabe","year":"1984","journal-title":"Dev. Growth Differ."},{"key":"2023090710501678800_DEVELOP_125_23_4835C17","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1101\/gad.10.10.1284","article-title":"Ptx1, a bicoid-related homeobox transcription factor involved in transcription of the pro-opiomelancortin gene","volume":"10","author":"Lamonerie","year":"1996","journal-title":"Genes Dev."},{"key":"2023090710501678800_DEVELOP_125_23_4835C18","doi-asserted-by":"crossref","first-page":"2807","DOI":"10.1242\/dev.124.14.2807","article-title":"The bicoid-related homeoprotein Ptx1 defines the most anterior domain of the embryo and differentiates posterior from anterior lateral mesoderm","volume":"124","author":"Lanctot","year":"1997","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C19","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1242\/dev.113.4.1093","article-title":"The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain","volume":"113","author":"Lazzaro","year":"1991","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C20","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/347528a0","article-title":"Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene Pit-1","volume":"347","author":"Li","year":"1990","journal-title":"Nature"},{"key":"2023090710501678800_DEVELOP_125_23_4835C21","first-page":"2876","volume":"13","author":"Li","year":"1994","journal-title":"Gsh-4 encodes a LIM-type homeodomain, is expressed in the developing central nervous system and is required for early postnatal survival. EMBO J"},{"key":"2023090710501678800_DEVELOP_125_23_4835C22","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ng0298-136","article-title":"An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination","volume":"18","author":"Meyers","year":"1998","journal-title":"Nat. Genet"},{"key":"2023090710501678800_DEVELOP_125_23_4835C23","first-page":"258","volume":"8","author":"Mucchielli","year":"1996","journal-title":"Otlx2, and Otx-related homeobox gene expressed in the pituitary gland and in a restricted pattern in the forebrain. Mol. Cell. Neurosci"},{"key":"2023090710501678800_DEVELOP_125_23_4835C24","doi-asserted-by":"crossref","first-page":"4045","DOI":"10.1242\/dev.121.12.4045","article-title":"Six3, a murine homologue of the sine ocularis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development","volume":"121","author":"Oliver","year":"1995","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C25","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0092-8674(00)80985-X","article-title":"Requirement for LIM homeobox gene Isl1 in motor neuron generation reveals a motor neuron-dependent step in interneuron differentiation","volume":"84","author":"Pfaff","year":"1996","journal-title":"Cell"},{"key":"2023090710501678800_DEVELOP_125_23_4835C26","first-page":"1183","article-title":"Spatially restricted expression of a member of a new family of murine Distal-less homeobox genes in the developing forebrain","volume":"3","author":"Robinson","year":"1991","journal-title":"New Biol"},{"key":"2023090710501678800_DEVELOP_125_23_4835C27","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1002\/aja.1000410206","article-title":"The development of the hypophysis cerebri of the albino rat","volume":"41","author":"Schwind","year":"1928","journal-title":"Am. J. Anat"},{"key":"2023090710501678800_DEVELOP_125_23_4835C28","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/ng1296-392","article-title":"Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome","volume":"14","author":"Semina","year":"1996","journal-title":"Nat. Genet"},{"key":"2023090710501678800_DEVELOP_125_23_4835C29","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1126\/science.272.5264.1004","article-title":"Specification of pituitary cell lineages by the LIM homeobox gene Lhx3","volume":"272","author":"Sheng","year":"1996","journal-title":"Science"},{"key":"2023090710501678800_DEVELOP_125_23_4835C30","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1126\/science.278.5344.1809","article-title":"Multistep control of pituitary organogenesis","volume":"278","author":"Sheng","year":"1997","journal-title":"Science"},{"key":"2023090710501678800_DEVELOP_125_23_4835C31","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1242\/dev.121.12.3923","article-title":"Longitudinal organization of the anterior neural plate and neural tube","volume":"121","author":"Shimamura","year":"1995","journal-title":"Development"},{"key":"2023090710501678800_DEVELOP_125_23_4835C32","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/384327a0","article-title":"Pituitary lineage determination by the prophet of Pit-1 homeodomain factor defective in Ames dwarfism","volume":"384","author":"Sornson","year":"1996","journal-title":"Nature"},{"key":"2023090710501678800_DEVELOP_125_23_4835C33","doi-asserted-by":"crossref","first-page":"7706","DOI":"10.1073\/pnas.93.15.7706","article-title":"P-OTX: a Pit-1-interacting homeodomain factor expressed during anterior pituitary gland development","volume":"93","author":"Szeto","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023090710501678800_DEVELOP_125_23_4835C34","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/S0955-0674(96)80085-8","article-title":"The hypothalamic-pituitary axis: co-development of two organs","volume":"8","author":"Treier","year":"1996","journal-title":"Current Opinion in Cell Biology"},{"key":"2023090710501678800_DEVELOP_125_23_4835C35","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1101\/gad.12.11.1691","article-title":"Multistep signaling requirements for pituitary organogenesis in vivo","volume":"12","author":"Treier","year":"1998","journal-title":"Genes Dev."},{"key":"2023090710501678800_DEVELOP_125_23_4835C36","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/BF00210884","article-title":"Effects of brain and mesenchyme upon the cytogenesis of rat adenohypophysis in vitro. Differentiation of adrenocorticotropes","volume":"227","author":"Watanabe","year":"1982","journal-title":"Cell Tiss. Res"},{"key":"2023090710501678800_DEVELOP_125_23_4835C37","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/BF00210885","article-title":"An organ culture study of the site of determination of ACTH and LH cells in the rat adenohypophysis","volume":"227","author":"Watanabe","year":"1982","journal-title":"Cell Tiss. Res"},{"key":"2023090710501678800_DEVELOP_125_23_4835C38","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0168-9525(98)01476-0","article-title":"How many homeobox genes does it take to make a pituitary gland?","volume":"14","author":"Watkins-Chow","year":"1998","journal-title":"Trends in Genet."},{"key":"2023090710501678800_DEVELOP_125_23_4835C39","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1101\/gad.9.17.2105","article-title":"Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse","volume":"9","author":"Winnier","year":"1995","journal-title":"Genes Dev."},{"key":"2023090710501678800_DEVELOP_125_23_4835C40","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0092-8674(00)80133-6","article-title":"The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4","volume":"86","author":"Zimmerman","year":"1996","journal-title":"Cell"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/125\/23\/4835\/3140894\/develop_125_23_4835.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/125\/23\/4835\/3140894\/develop_125_23_4835.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T06:53:19Z","timestamp":1694069599000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/125\/23\/4835\/40149\/Formation-of-Rathke-s-pouch-requires-dual"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,12,1]]},"references-count":40,"journal-issue":{"issue":"23","published-print":{"date-parts":[[1998,12,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.125.23.4835","relation":{},"ISSN":["0950-1991","1477-9129"],"issn-type":[{"value":"0950-1991","type":"print"},{"value":"1477-9129","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,12,1]]}}}