Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile Tilapia

The evolutionary loss of <i>ednrb2</i> in specific vertebrate lineages, such as mammals and cypriniform fish, raises fundamental questions about its functional necessity and potential redundancy or synergy with paralogous endothelin receptors in pigment cell development. In teleosts poss...

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Main Authors: Zilong Wen, Jinzhi Wu, Jiawen Yao, Fugui Fang, Siyu Ju, Chenxu Wang, Xingyong Liu, Deshou Wang
Format: Article
Language:English
Published: MDPI AG 2025-08-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/15/1213
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author Zilong Wen
Jinzhi Wu
Jiawen Yao
Fugui Fang
Siyu Ju
Chenxu Wang
Xingyong Liu
Deshou Wang
author_facet Zilong Wen
Jinzhi Wu
Jiawen Yao
Fugui Fang
Siyu Ju
Chenxu Wang
Xingyong Liu
Deshou Wang
author_sort Zilong Wen
collection DOAJ
description The evolutionary loss of <i>ednrb2</i> in specific vertebrate lineages, such as mammals and cypriniform fish, raises fundamental questions about its functional necessity and potential redundancy or synergy with paralogous endothelin receptors in pigment cell development. In teleosts possessing both <i>ednrb1a</i> and <i>ednrb2</i> (e.g., Nile tilapia), their respective and combined roles in regulating neural crest-derived pigment cell precursors remains unresolved. Using CRISPR/Cas9, we generated single and double <i>ednrb</i> mutants to dissect their functions. We demonstrated that <i>ednrb1a</i> and <i>ednrb2</i> synergistically govern the differentiation and migration of iridophore precursors. While <i>ednrb1a</i> is broadly essential for iridophore development, <i>ednrb2</i> plays a unique and indispensable role in the colonization of iridophores in the dorsal iris. Double mutants exhibit near-complete iridophore loss; severe depletion of melanophores, xanthophores, and erythrophores; and a striking, fertile, transparent phenotype. Crucially, this iridophore deficiency does not impair systemic guanine synthesis pathways. mRNA rescue experiments confirmed <i>mitfa</i> as a key downstream effector within the Ednrb signaling cascade. This work resolves the synergistic regulation of pigment cell fates by Ednrb receptors and establishes a mechanism for generating transparent ermplasm.
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spelling doaj-art-9ec9f611bca04241b8b70831c6783c7d2025-08-20T04:00:54ZengMDPI AGCells2073-44092025-08-011415121310.3390/cells14151213Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile TilapiaZilong Wen0Jinzhi Wu1Jiawen Yao2Fugui Fang3Siyu Ju4Chenxu Wang5Xingyong Liu6Deshou Wang7Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaIntegrative Science Center of Germplasm Creation in Western China (Chongqing) Science City, Southwest University, Chongqing 400715, ChinaThe evolutionary loss of <i>ednrb2</i> in specific vertebrate lineages, such as mammals and cypriniform fish, raises fundamental questions about its functional necessity and potential redundancy or synergy with paralogous endothelin receptors in pigment cell development. In teleosts possessing both <i>ednrb1a</i> and <i>ednrb2</i> (e.g., Nile tilapia), their respective and combined roles in regulating neural crest-derived pigment cell precursors remains unresolved. Using CRISPR/Cas9, we generated single and double <i>ednrb</i> mutants to dissect their functions. We demonstrated that <i>ednrb1a</i> and <i>ednrb2</i> synergistically govern the differentiation and migration of iridophore precursors. While <i>ednrb1a</i> is broadly essential for iridophore development, <i>ednrb2</i> plays a unique and indispensable role in the colonization of iridophores in the dorsal iris. Double mutants exhibit near-complete iridophore loss; severe depletion of melanophores, xanthophores, and erythrophores; and a striking, fertile, transparent phenotype. Crucially, this iridophore deficiency does not impair systemic guanine synthesis pathways. mRNA rescue experiments confirmed <i>mitfa</i> as a key downstream effector within the Ednrb signaling cascade. This work resolves the synergistic regulation of pigment cell fates by Ednrb receptors and establishes a mechanism for generating transparent ermplasm.https://www.mdpi.com/2073-4409/14/15/1213<i>ednrb</i>pigment cell precursorssynergistic regulationguanineerythrophoresheritable
spellingShingle Zilong Wen
Jinzhi Wu
Jiawen Yao
Fugui Fang
Siyu Ju
Chenxu Wang
Xingyong Liu
Deshou Wang
Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile Tilapia
Cells
<i>ednrb</i>
pigment cell precursors
synergistic regulation
guanine
erythrophores
heritable
title Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile Tilapia
title_full Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile Tilapia
title_fullStr Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile Tilapia
title_full_unstemmed Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile Tilapia
title_short Synergistic Regulation of Pigment Cell Precursors’ Differentiation and Migration by <i>ednrb1a</i> and <i>ednrb2</i> in Nile Tilapia
title_sort synergistic regulation of pigment cell precursors differentiation and migration by i ednrb1a i and i ednrb2 i in nile tilapia
topic <i>ednrb</i>
pigment cell precursors
synergistic regulation
guanine
erythrophores
heritable
url https://www.mdpi.com/2073-4409/14/15/1213
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AT jiawenyao synergisticregulationofpigmentcellprecursorsdifferentiationandmigrationbyiednrb1aiandiednrb2iinniletilapia
AT fuguifang synergisticregulationofpigmentcellprecursorsdifferentiationandmigrationbyiednrb1aiandiednrb2iinniletilapia
AT siyuju synergisticregulationofpigmentcellprecursorsdifferentiationandmigrationbyiednrb1aiandiednrb2iinniletilapia
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AT xingyongliu synergisticregulationofpigmentcellprecursorsdifferentiationandmigrationbyiednrb1aiandiednrb2iinniletilapia
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