Journal
DEVELOPMENTAL BIOLOGY
Volume 313, Issue 1, Pages 118-129Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2007.10.006
Keywords
Isl1; Sf1; NR5A1; Notch2; Tpit; Neurod1; Tle3; Pitx1; Pitx2; LIM3; P-LIM
Categories
Funding
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R01HD034283] Funding Source: NIH RePORTER
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT [T32HD007048, R37HD030428, F32HD046300] Funding Source: NIH RePORTER
- NICHD NIH HHS [R37 HD030428-16, F32 HD046300, F32-HD046300-01, T32-HD7048-28, R01 HD034283, R01 HD034283-13, R01-HD34283, T32 HD007048, R37-HD30428, R37 HD030428] Funding Source: Medline
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The LIM homeodomain transcription factor, LHX3, is essential for pituitary development in mouse and man. Lhx3 engineered null mice have profound pituitary hypoplasia that we find is attributable to an increase in cell death early in pituitary development. Dying cells are localized to regions of TPIT expression indicating that cell death may contribute to the severe reduction in differentiated corticotrope cells and lower expression of the corticotrope transcription factors, TPIT and NEUROD1. Lhx3 deficiency also results in dorsal ectopic expression of transcription factors characteristic of gonadotropes, SF1 and ISL1, but no gonadotropin expression. This apparent disturbance of cell differentiation may be due, in part, to loss of NOTCH2. NOTCH2 is normally expressed in the pituitary at the boundary between dorsal, proliferating cells and ventral, differentiating cells and is important for maintaining dorsal-ventral patterning in other organs. Thus, Lhx3 contributes significantly to pituitary development by maintaining normal dorsal-ventral patterning, cell survival, and normal expression of corticotrope-specific transcription factors, which are necessary for repressing ectopic gonadotrope differentiation. Published by Elsevier Inc.
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