In:
Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-2-7)
Abstract:
ISL LIM homeobox 2, also known as insulin gene enhancer protein ISL-2 ( ISL2 ), is a transcription factor gene that participates in a wide range of developmental events. However, the role of ISL2 in the hypothalamus-pituitary-thyroid axis is largely unknown. In the present study, we characterized the expression patterns of ISL2 and revealed its regulative role during embryogenesis using zebrafish. Methods We used the CRISPR/Cas9 system to successfully establish homozygous ISL2 -orthologue ( isl2a and isl2b ) knockout zebrafish. Moreover, we utilized these knockout zebrafish to analyze the pituitary and thyroid phenotypes in vivo . For further molecular characterization, in situ hybridization and immunofluorescence were performed. Results The isl2a mutant zebrafish presented with thyroid hypoplasia, reduced whole-body levels of thyroid hormones, increased early mortality, gender imbalance, and morphological retardation during maturity. Additionally, thyrotropes, a pituitary cell type, was notably decreased during development. Importantly, the transcriptional levels of pituitary-thyroid axis hormones-encoding genes, such as tshba , cga , and tg , were significantly decreased in isl2a mutants. Finally, the thyroid dysplasia in isl2a mutant larvae may be attributed to a reduction in proliferation rather than changes in apoptosis. Conclusions In summary, isl2a regulates the transcriptional levels of marker genes in hypothalamus-pituitary-thyroid axis, and isl2a knockout causing low thyroid hormone levels in zebrafish. Thus, isl2a identified by the present study, is a novel regulator for pituitary cell differentiation in zebrafish, resulting in thyroid gland hypoplasia and phenotypes of hypothyroidism.
Type of Medium:
Online Resource
ISSN:
1664-2392
DOI:
10.3389/fendo.2023.920548
DOI:
10.3389/fendo.2023.920548.s001
DOI:
10.3389/fendo.2023.920548.s002
DOI:
10.3389/fendo.2023.920548.s003
DOI:
10.3389/fendo.2023.920548.s004
DOI:
10.3389/fendo.2023.920548.s005
DOI:
10.3389/fendo.2023.920548.s006
DOI:
10.3389/fendo.2023.920548.s007
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2023
detail.hit.zdb_id:
2592084-4
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