Lack of the ventral anterior homeodomain transcription factor VAX1 leads to induction of a second pituitary.
The pituitary gland is an endocrine organ that is developmentally derived from a fold in the oral ectoderm and a juxtaposed fold in the neural ectoderm. Here, we show that the absence of Vax1, a homeodomain transcription factor known for its role in eye and optic chiasm development, causes the rostral oral ectoderm to form an ectopic fold that eventually develops into a separate second pituitary with all the pituitary cell types and neuronal fibers characteristic of the normal pituitary. The induction of the second pituitary is associated with a localized ectopic expression of Fgf10, a gene encoding a growth factor known to recruit oral ectodermal cells into the pituitary. Interestingly, there are rare cases of pituitary duplications in humans that are also associated with optic nerve dysplasia, suggesting that VAX1 might be involved in the pathogenesis of this disorder.
Mammalian Development Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-3706, USA. kapilbharti@mail.nih.gov
Kapil
K
Bharti
Melanie
M
Gasper
Stefano
S
Bertuzzi
Heinz
H
Arnheiter
D000818:Animals; D004475:Ectoderm / Q000166:cytology*; D051526:Fibroblast Growth Factor 10 / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009412:Nerve Fibers; D009479:Neuropeptides / Q000172:deficiency*; D009901:Optic Nerve Diseases / Q000209:etiology; D010902:Pituitary Gland / Q000254:growth & development* / Q000294:innervation; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D018398:Homeodomain Proteins; D009479:Neuropeptides; D014157:Transcription Factors; C572055:VAX1 protein, human; C485177:Vax1 protein, mouse
Dev Biol. 2007 Nov 15;311(2):396-407
17919533
Genes Dev. 2005 May 15;19(10):1249-59
15905411
Genes Dev. 1998 Jun 1;12(11):1691-704
9620855
Dev Biol. 2009 Aug 15;332(2):383-95
19520072
Physiol Rev. 2007 Jul;87(3):933-63
17615393
Development. 2002 Jan;129(2):329-37
11807026
Peptides. 1988 Jan-Feb;9(1):87-105
3362746
Mol Cell Endocrinol. 2010 Jul 8;323(1):4-19
20025935
Neuroradiology. 2004 Dec;46(12):1036-8
15565346
Proc Natl Acad Sci U S A. 2005 Oct 11;102(41):14700-5
16203978
J Histochem Cytochem. 1994 Aug;42(8):1117-25
8027530
Development. 1998 Jul;125(14):2599-610
9636075
Mol Endocrinol. 2005 Jul;19(7):1893-903
15761027
Genes Dev. 1999 Dec 1;13(23):3092-105
10601035
Mol Endocrinol. 2004 May;18(5):1196-209
14988429
Cell. 1999 May 28;97(5):587-98
10367888
Endocr Dev. 2009;14:114-34
19293579
Development. 2001 Feb;128(3):377-86
11152636
Genes Dev. 2003 Mar 15;17(6):738-47
12651892
J Neurosci. 2006 Jan 11;26(2):550-8
16407553
Peptides. 1988 Sep-Oct;9(5):1151-75
3072535
Development. 1995 Dec;121(12):4045-55
8575305
Ann Med. 2006;38(8):560-77
17438671
Science. 1996 May 17;272(5264):1004-7
8638120
FASEB J. 2002 Jun;16(8):869-71
11967234
Development. 2008 Mar;135(6):1169-78
18272592
Endocr Rev. 2009 Dec;30(7):790-829
19837867