The HMG-Box Transcription Factor Sox4b Is Required for Pituitary Expression of gata2a and Specification of Thyrotrope and Gonadotrope Cells in Zebrafish

The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box...

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Published in:Molecular endocrinology (Baltimore, Md.) Md.), 2012-06, Vol.26 (6), p.1014-1027
Main Authors: Quiroz, Yobhana, Lopez, Mauricio, Mavropoulos, Anastasia, Motte, Patrick, Martial, Joseph A, Hammerschmidt, Matthias, Muller, Marc
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Biochemistry, biophysics & molecular biology
Biochimie, biophysique & biologie moléculaire
Danio rerio
Follicle Stimulating Hormone, beta Subunit - genetics
Follicle Stimulating Hormone, beta Subunit - metabolism
Freshwater
GATA2 Transcription Factor - genetics
GATA2 Transcription Factor - metabolism
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Glycoprotein Hormones, alpha Subunit - genetics
Glycoprotein Hormones, alpha Subunit - metabolism
Gonadotrophs - metabolism
Gonadotrophs - physiology
HMGB Proteins - genetics
HMGB Proteins - metabolism
HMGB Proteins - physiology
Life sciences
Luteinizing Hormone, beta Subunit - genetics
Luteinizing Hormone, beta Subunit - metabolism
Morpholinos - genetics
Mucolipidoses
Organogenesis
Original Research
Pituitary Gland, Anterior - cytology
Pituitary Gland, Anterior - embryology
Pituitary Gland, Anterior - metabolism
Sciences du vivant
Thyrotrophs - metabolism
Thyrotrophs - physiology
Thyrotropin, beta Subunit - genetics
Thyrotropin, beta Subunit - metabolism
Transcription, Genetic
Zebrafish - embryology
Zebrafish - genetics
Zebrafish - metabolism
Zebrafish Proteins - genetics
Zebrafish Proteins - metabolism
Zebrafish Proteins - physiology
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Summary:The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.
ISSN:0888-8809
1944-9917
1944-9917
DOI:10.1210/me.2011-1319