近日，華中農(nóng)業(yè)大學(xué)水產(chǎn)學(xué)院魚類遺傳育種與繁育實(shí)驗(yàn)室高澤霞教授課題組以模式生物斑馬魚為研究對(duì)象，揭示了魚類骨形態(tài)發(fā)生蛋白 7 （BMP7） 中bmp7a和bmp7b亞型功能上的分化。相關(guān)研究成果以“Functional differentiation of bmp7 genes in zebrafish: bmp7a for dorsal-ventral pattern and bmp7b for melanin synthesis and eye development”為題在Frontiers in Cell and Developmental Biology發(fā)表。

 

　　曾有科學(xué)研究揭示，骨形態(tài)發(fā)生蛋白 7 （BMP7） 屬于轉(zhuǎn)化生長(zhǎng)因子 β （TGF-β） 家族，不僅能誘導(dǎo)軟骨和骨形成，還能調(diào)節(jié)哺乳動(dòng)物的眼睛發(fā)育和黑色素瘤的發(fā)生（Luo et al 1995；Rothhammer et al 2005；Lavery et al 2009）。硬骨魚中BMP7分化為了bmp7a和bmp7b亞型，我校科研人員認(rèn)為硬骨魚中bmp7a和bmp7b各自發(fā)揮什么樣的作用很值得探究。

 

　　在研究中，我?？蒲袌F(tuán)隊(duì)通過(guò)CRISPR/Cas9介導(dǎo)的基因敲除技術(shù)在斑馬魚中構(gòu)建了bmp7a和bmp7b純合突變品系。發(fā)現(xiàn)其中bmp7a-/-突變體胚胎的背腹模式發(fā)育異常，從而在胚胎期發(fā)生死亡。Bmp7b-/- 突變體生長(zhǎng)受到抑制，皮膚和眼睛視網(wǎng)膜中黑色素增多，攝食行為受到阻礙。

 

　　研究人員進(jìn)一步探究了Bmp7b-/- 突變體的皮膚和眼組織的轉(zhuǎn)錄組的相關(guān)調(diào)控機(jī)制，認(rèn)為wnt7ba和gna14等基因的表達(dá)變化可能促進(jìn)黑色素的增加，而眼睛結(jié)構(gòu)的變化導(dǎo)致光轉(zhuǎn)導(dǎo)缺陷，并且 7 個(gè) DEGs（rgs9a、rgs9b、rcvrn2、guca1d、grk1b、opn1mw4 和 gc2）被確定為關(guān)鍵候選基因，影響眼睛的光響應(yīng)。

 

　　通過(guò)這項(xiàng)研究，科研人員揭示了bmp7a和bmp7b在硬骨魚中的功能分化，首次報(bào)道bmp7b對(duì)黑色素生成的抑制作用，并認(rèn)為這項(xiàng)發(fā)現(xiàn)可能為未來(lái)人類黑色素瘤相關(guān)疾病的研究提供有用的信息。

 

　　該研究獲得了湖北洪山實(shí)驗(yàn)室、國(guó)家現(xiàn)代農(nóng)業(yè)產(chǎn)業(yè)技術(shù)體系、國(guó)家自然科學(xué)基金等項(xiàng)目的支持。

 

　　【英文摘要】

 

　　Bone morphogenetic protein 7 （BMP7） belongs to the transforming growth factor β （TGF-β） family, which not only induces cartilage and bone formation, but also regulates eye development and melanoma tumorigenesis in mammals. In teleosts, BMP7 differentiates into two subtypes, bmp7a and bmp7b, which have clearly differentiated structures. To fully understand the functional differentiation of bmp7a and bmp7b in fish species, we successfully constructed bmp7a and bmp7b gene deletion mutants in zebrafish using CRISPR/Cas9-mediated gene editing technology. Our results showed that bmp7a mutation caused abnormal development of the embryo's dorsal-ventral pattern that led to death; bmp7b mutation induced growth inhibition and increased melanin production in the skin and eye of mutants. Histological analysis revealed that melanin in the retina of the eyes in bmp7b mutants increased, and behavioral observation showed that the vision and sensitivity to food of the mutants were reduced. Transcriptome analysis of the skin and eye tissues showed that the expression changes of wnt7ba and gna14 in bmp7b mutants might promote the increase of melanin. Additionally, the eye transcriptome analysis indicated that changes in the structure of the eyes in bmp7b mutants led to defects in phototransduction, and seven DEGs （rgs9a, rgs9b, rcvrn2, guca1d, grk1b, opn1mw4, and gc2） were identified as key candidate genes that affected the photonic response of the eyes. The study revealed the functional differentiation of bmp7a and bmp7b in teleosts and the first report about the inhibitory effect of bmp7b on melanogenesis may provide useful information for the future research on human melanoma-related diseases.

 

　　論文鏈接：https://doi: 10.3389/fcell.2022.838721