Aberrant Global and Jagged-Mediated Notch Signaling Disrupts Segregation Between wt1-Expressing and Steroidogenic Tissues in Zebrafish

Abstract

Although the zebrafish interrenal tissue has been used as a model for steroidogenesis and genesis of the adrenal gland, its specification and morphogenesis remains largely unclear. In the present study, we explored how the Wilms tumor 1 (WT1)-expressing cells are segregated from the SF-1-expressing steroidogenic cells in the zebrafish model. The interrenal tissue precursors expressing ff1b, the equivalent of mammalian SF-1, were derived from wt1-expressing pronephric primordia in the zebrafish embryo. Through histochemistry and in situ hybridization, we demonstrated that the size of functionally differentiated interrenal tissue was substantially increased on global inhibition of the Notch signaling pathway and was accompanied by a disrupted segregation between the wt1- and ff1b-expressing cells. As the Notch pathway was conditionally activated during interrenal specification, differentiation, but not ff1b expression, of interrenal tissue was drastically compromised. In embryos deficient for Notch ligands jagged 1b and 2b, transgenic reporter activity of wt1b promoter was detected within the steroidogenic interrenal tissue. In conclusion, our results indicate that Jagged-Notch signaling is required (1) for segregation between wt1-expressing cells and differentiated steroidogenic tissue; and (2) to modulate the extent of functional differentiation in the steroidogenic interrenal tissue.

Genetic mechanism underlying sexual plasticity and its association with colour patterning in zebrafish (Danio rerio)

“…Most studies on the function of wt1 in zebrafish have been focused on the embryonic kidney, the pronephros, development [31, 32]. However, Wt1 is necessary for urogenital ridge development and identifying the adrenal-gonadal primordium (AGP), and both paralogous are seems to be required for kidney and gonad development in zebrafish [45]. These paralogous have a clear role in pronephric glomerular formation of kidney during embryonic development in zebrafish.…”

“…In adult zebrafish, a high expression level of both wt1 genes can be found in the kidney, gonad, heart, spleen, and muscle tissues [30, 31]. Expression of wt1 at AGP is essential for the steroidogenic interrenal cells development in cooperation with ff1b ( nr5a1a ) gene (the equivalent of mammalian SF-1 ), suggesting its important role during development of gonadal primordium in zebrafish [45–47]. In a recent study, expression of wt1a gene was observed in the zebrafish testis and is identified as a pro-male gene [48].…”

Delta/Jagged-mediated Notch signaling induces the differentiation of agr2-positive epidermal mucous cells in zebrafish embryos

“…Various morpholio oligonucleotides (MOs) from Gene Tools used in this study were as follows: dlc MO: 5’-CGATAGCAGACTGTGAGAGTAGTCC -3’, 4.9 ng [ 31 ]; foxi3a ATGMO: 5’-AGACTGTGGAACAAATGATGTCATG -3’, 4.3 ng [ 14 ]; foxi3a misMO: 5’-AGA G TGTG C AAGAAAT C ATGT G ATG-3’, 4.3 ng (mismatched sequence is italized) [ 14 ]; grhl1 ATGMO: 5’-GTGACATCTCTTATGGTCGAACTGG-3’, 3 ng [ 21 ]; grhl1 SPMO: 5’-CTTTGATGAGAGCTTCACCTTTTGT-3’, 3 ng [ 21 ]; jag1a UTRMO: 5’- CGGTTTGTCTGTCTGTGTGTCTGTC-3’, 0.5 ng [ 41 ]; jag1a SPMO: 5’- ATAAAAGATACTCACTGCCAGTGCT-3’, 1.0 ng; jag1b UTRMO: 5’- TCACGGCTCTAATGTACTCCCCGAT-3’, 1.2 ng [ 42 ]; jag2a MO: 5’- CTCCAAAATAGTTATG CAT GACTCC-3’, 4 ng (start codon is underlined); notch3 UTRMO: 5’-ACATCCTTTAAGAAATGAATCGGCG-3’, 0.8 ng [ 43 ]; notch3 SPMO: 5’- AAGGATCAGTCATCTTACCTTCGCT-3’, 2 ng [ 43 ] Various MOs were diluted in Danieau solution and individually injected into the cytoplasm of one- or two-cell zygotes.…”

Genotype by temperature interaction effects on sex determination in zebrafish (Danio rerio)

“…Most studies on the function of wt1 in zebrafish have been focused on the embryonic kidney, the pronephros, development (Bolling et al, 2006;Perner et al, 2007). However, Wt1 is necessary for urogenital ridge development and identifying the adrenal-gonadal primordium (AGP), and both paralogous are seems to be required for kidney and gonad development in zebrafish (Chou et al, 2017). These paralogous have a clear role in pronephric glomerular formation of kidney during embryonic development in zebrafish.…”

“…In adult zebrafish, a high expression level of both wt1 genes can be found in the kidney, gonad, heart, spleen, and muscle tissues (Schnerwitzki et al, 2014;Bolling et al, 2006). Expression of wt1 at AGP is essential for the steroidogenic interrenal cells development in cooperation with ff1b (nr5a1a) gene (the equivalent of mammalian SF-1), suggesting its important role during development of gonadal primordium in zebrafish (Chou et al, 2017, Hsu et al, 2003, von Hofsten and Olsson, 2005.…”