Limits...
ZBTB20 is required for anterior pituitary development and lactotrope specification.

Cao D, Ma X, Cai J, Luan J, Liu AJ, Yang R, Cao Y, Zhu X, Zhang H, Chen YX, Shi Y, Shi GX, Zou D, Cao X, Grusby MJ, Xie Z, Zhang WJ - Nat Commun (2016)

Bottom Line: Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes.Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ.In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.

ABSTRACT
The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20- mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

No MeSH data available.


Related in: MedlinePlus

Defect of lactotropes specification and differentiation in the absence of ZBTB20.(a) Immunohistochemical double staining of PRL (green) and GH (red) in the pituitaries from Zbtb20+/+ and Zbtb20−/− mice at the age from E16.5 to P4. Cell nuclei were stained with DAPI (blue). Arrowheads indicate PRL and GH double-positive cells. Scale bar, 25 μm. (b,c) The percentages of double-positive cells (b) and PRL single-positive cells (c) among the PRL-positive cells in the pituitaries of wild-type mice are shown by diagram. E15.5: n=28 sections from four animals; E16.5: n=23 sections from five animals; E18.5: n=15 sections from four animals; P0: n=21 sections from five animals; P4: n=26 sections from five5 animals; P7: n=24 sections from four animals; and P14: n=13 sections from two animals. Values represent mean±s.e.m. *P<0.05 versus control (Student's t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835541&req=5

f3: Defect of lactotropes specification and differentiation in the absence of ZBTB20.(a) Immunohistochemical double staining of PRL (green) and GH (red) in the pituitaries from Zbtb20+/+ and Zbtb20−/− mice at the age from E16.5 to P4. Cell nuclei were stained with DAPI (blue). Arrowheads indicate PRL and GH double-positive cells. Scale bar, 25 μm. (b,c) The percentages of double-positive cells (b) and PRL single-positive cells (c) among the PRL-positive cells in the pituitaries of wild-type mice are shown by diagram. E15.5: n=28 sections from four animals; E16.5: n=23 sections from five animals; E18.5: n=15 sections from four animals; P0: n=21 sections from five animals; P4: n=26 sections from five5 animals; P7: n=24 sections from four animals; and P14: n=13 sections from two animals. Values represent mean±s.e.m. *P<0.05 versus control (Student's t-test).

Mentions: To further characterize the developmental defect of lactotrope lineage in ZBTB20- mice, we examined its ontogeny during embryonic and early postnatal periods. The lactotrope lineage emerges at E15.5 in mice, characterized by the expression of PRL in a restricted medial zone adjacent to the ventral surface of the intermediate lobe2, and undergoes rapid expansion during P7 to P21. Thus we first detected PRL expression in the developing pituitary. Consistently, immunohistochemical staining revealed that PRL-reactive cells were not detected at all in the mutant pituitary from P4 to P7 (Fig. 3a; Supplementary Fig. 3a). In addition, Prl mRNA expression was hardly detectable by RT–PCR after P2 (Supplementary Fig. 3b). Surprisingly, sparse PRL-immunoreactive cells were transiently detected in mutant pituitaries from E15.5 to birth, with no significant difference compared to control group (Fig. 3a; Supplementary Fig. 4). Moreover, Prl mRNA expression was also detected in mutant pituitary at birth, although the levels were decreased by ∼70% compared with control (Supplementary Fig. 3b). These data suggest that lactotrope lineage could be transiently initiated in Zbtb20- pituitary in the perinatal period.


ZBTB20 is required for anterior pituitary development and lactotrope specification.

Cao D, Ma X, Cai J, Luan J, Liu AJ, Yang R, Cao Y, Zhu X, Zhang H, Chen YX, Shi Y, Shi GX, Zou D, Cao X, Grusby MJ, Xie Z, Zhang WJ - Nat Commun (2016)

Defect of lactotropes specification and differentiation in the absence of ZBTB20.(a) Immunohistochemical double staining of PRL (green) and GH (red) in the pituitaries from Zbtb20+/+ and Zbtb20−/− mice at the age from E16.5 to P4. Cell nuclei were stained with DAPI (blue). Arrowheads indicate PRL and GH double-positive cells. Scale bar, 25 μm. (b,c) The percentages of double-positive cells (b) and PRL single-positive cells (c) among the PRL-positive cells in the pituitaries of wild-type mice are shown by diagram. E15.5: n=28 sections from four animals; E16.5: n=23 sections from five animals; E18.5: n=15 sections from four animals; P0: n=21 sections from five animals; P4: n=26 sections from five5 animals; P7: n=24 sections from four animals; and P14: n=13 sections from two animals. Values represent mean±s.e.m. *P<0.05 versus control (Student's t-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835541&req=5

f3: Defect of lactotropes specification and differentiation in the absence of ZBTB20.(a) Immunohistochemical double staining of PRL (green) and GH (red) in the pituitaries from Zbtb20+/+ and Zbtb20−/− mice at the age from E16.5 to P4. Cell nuclei were stained with DAPI (blue). Arrowheads indicate PRL and GH double-positive cells. Scale bar, 25 μm. (b,c) The percentages of double-positive cells (b) and PRL single-positive cells (c) among the PRL-positive cells in the pituitaries of wild-type mice are shown by diagram. E15.5: n=28 sections from four animals; E16.5: n=23 sections from five animals; E18.5: n=15 sections from four animals; P0: n=21 sections from five animals; P4: n=26 sections from five5 animals; P7: n=24 sections from four animals; and P14: n=13 sections from two animals. Values represent mean±s.e.m. *P<0.05 versus control (Student's t-test).
Mentions: To further characterize the developmental defect of lactotrope lineage in ZBTB20- mice, we examined its ontogeny during embryonic and early postnatal periods. The lactotrope lineage emerges at E15.5 in mice, characterized by the expression of PRL in a restricted medial zone adjacent to the ventral surface of the intermediate lobe2, and undergoes rapid expansion during P7 to P21. Thus we first detected PRL expression in the developing pituitary. Consistently, immunohistochemical staining revealed that PRL-reactive cells were not detected at all in the mutant pituitary from P4 to P7 (Fig. 3a; Supplementary Fig. 3a). In addition, Prl mRNA expression was hardly detectable by RT–PCR after P2 (Supplementary Fig. 3b). Surprisingly, sparse PRL-immunoreactive cells were transiently detected in mutant pituitaries from E15.5 to birth, with no significant difference compared to control group (Fig. 3a; Supplementary Fig. 4). Moreover, Prl mRNA expression was also detected in mutant pituitary at birth, although the levels were decreased by ∼70% compared with control (Supplementary Fig. 3b). These data suggest that lactotrope lineage could be transiently initiated in Zbtb20- pituitary in the perinatal period.

Bottom Line: Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes.Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ.In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.

ABSTRACT
The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20- mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

No MeSH data available.


Related in: MedlinePlus