四十年一以贯之的研究特征：基因与功能

1）神经发育的分子机理

1-1）克隆果蝇神经母细胞与表皮母细胞命运的基因big brain(分子生物学克隆基因)

Rao Y, Jan LY and Jan YN (1990). Similarity of the product of the Drosophila neurogenic genebig brainto transmembrane channel proteins.Nature345:163-167.

1-2）果蝇的中胚层不诱导神经外胚层、但影响其位置(遗传、发育)

Rao Y, Vaessin H, Jan LY and Jan YN (1991). Neuroectoderm in Drosophila embryos is dependent on the mesoderm for the positioning but not for formation.Genes Dev5:1577-1588.

1-3）果蝇big brain基因确定神经细胞前体的数量(遗传、发育)

Rao Y, Bodmer R, Jan LY and Jan YN (1992). Thebig braingene of Drosophila functions to control the number of neuronal precursors in the peripheral nervous system.Development116:31-40.

1-4）分子影响爪蟾胚胎中胚层与神经胚层(基因、发育)

Rao Y (1994). Conversion of a mesodermalizing molecule, the Xenopus Brachyury gene, into a neuralizing factor.Genes Dev.8:939-947.

1-5）影响作为信号的爪蟾分泌蛋白(基因、发育)

Wu JY, Wen L, Zhang, WJ and Rao Y (1996). The secreted product of Xenopuslunatic fringe, a vertebrate signaling molecule.Science273:355-358.

1-6）中胚层如何影响外胚层的眼形态发生场形成两个眼睛(发育、观察基因表达)

Li HS, Tierney C, Wen L, Wu JY and Rao Y (1997). A single morphogenetic field gives rise to two retina primordia under the influence of the prechordal mesoderm.Development124:603-615.

1-7）分泌型蛋白质Slit作为Roundabout膜蛋白的配体而对轴突导向起排斥性作用(基因、蛋白质结合、神经纤维)

Li HS, Chen JH, Wu W, Fagaly T, Yuan WL, Zhou L, Dupuis S, Jiang Z, Nash W, Gick C, Ornitz D, Wu JY and Rao Y (1999). Vertebrate Slit, a secreted ligand for the transmembrane protein Roundabout, is a repellent for olfactory bulb axons.Cell96:807-818.

1-8）分泌型蛋白质Slit导向嗅觉系统神经细胞迁移(基因、脑切片活体培养)

Wu W, Wong K, Chen JH, Jiang ZH, Dupuis S, Wu JY and Rao Y (1999).Directional guidance of neuronal migration in the olfactory system by the secreted protein Slit.Nature400:331-336.

1-9）分泌型蛋白质Slit导向大脑皮层神经细胞迁移(基因、神经细胞)

Zhu Y, Li HS, Zhou L, Wu JY and Rao Y (1999).Cellular and molecular guidance of GABAergic neuronal migration from an extra-cortical origin to the neocortex.Neuron23: 473-485.

1-10）ET是转录抑制因子(基因功能)

He M, Wen L, Campbell C, Wu JY and Rao Y (1999). Transcription repression by ET, an ortholog of human Tbx3, a gene involved in ulnar-mammary syndrome.Proc Natl Acad Sci96:10212-10217.

1-11）分泌型蛋白质Slit的在爪蟾胚胎的表达和蛋白质分泌(非功能研究)

Chen J, Wu W, Li HS, Fagaly T, Zhou L, Wu JY and Rao Y (2000).Embryonic expression and extracellular secretion of Xenopus Slit.Neuroscience96:231-236.

1-12）分泌型蛋白质Slit的N末端足以导向轴突和神经细胞迁移(基因、神经细胞)

Chen J, Wen L, Dupuis S, WuJY andRao Y (2001).The N-terminal leucine rich regions inSlitare sufficient to repel olfactory bulbaxons and subventricular zone neurons.J Neurosci21:1548-1556.

1-13）嗅球轴突短程独立于Slit(神经细胞)

Hirata T, Fujisawa H, Wu JY and Rao Y (2001). Independence of short-range guidance for olfactory bulb axons from repulsive factor Slit.J Neurosci21: 2373-2379.

1-14）分泌型蛋白质Slit导向神经细胞迁移(基因、白细胞)

Wu JY, Feng L, Park H-T, HavliogluN,Wen L, Tang H, Bacon KB, Jiang Z, Zhang X-C and Rao Y (2001).The neuronal repellentSlit inhibits leukocyte chemotaxis induced by chemotactic factors.Nature410:948-952.

1-15）Slit的信号转导通路GTP酶(基因、神经细胞)

Wong K, Ren X-R, Huang Y-Z, Xie Y, Liu G, Saito H, Tang H, Wen L, Brady-Kalnay SM, Mei L, Wu JY, Xiong W-C and Rao Y (2001). Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.Cell107:209-221.

1-16）SDF蛋白质导向小脑神经细胞(基因、神经细胞)

Zhu Y, Yu T, Zhang X-C, Nagasawa T,Wu JY and Rao Y (2002).Role of the chemokine SDF-1 as the meningeal attractant for embryonic cerebellar neurons.Nat Neurosci5:719-720.

1-17）区分神经细胞导向和运动性(神经细胞运动)

Ward M, McCann C, DeWulf M, Wu JY and Rao Y (2003). Distinguishing between directional guidance and motility regulation in neuronal migration. J Neurosci23:5170-5177.

神经细胞迁移的新的吸引性分子(神经细胞)

Liu G and Rao Y (2003).Neuronal migration from the forebrain to the olfactory bulb requires a new attractant persistent in the olfactory bulb.J Neurosci 23：6651-6659.  

1-18）小脑神经细胞迁移过程对脑膜反应的变化(基因、神经细胞)

Zhu Y, Yu T and Rao Y (2004).Developmental regulation of EGLmigration through aswitch in cellular responsivenessto cerebellar meninges. Dev Biol 267:153-64.

1-19）导向分子netrin下游需要两种蛋白激酶起吸引作用(基因、神经细胞)

Liu G, Beggs H, Jürgensen C, Park HT, Tang H, GorskiJ,JonesKR,Reichardt LF, Wu JY and Rao Y (2004).Netrinrequiresthe focal adhesion kinase and the Src family kinasesto induceaxon outgrowth and to attract axons.Nat Neurosci7:1222-1232.

1-20）GSK蛋白激酶参与神经细胞极性形成和维持(基因、神经细胞)

Jiang H, Guo W, Liang XH and Y Rao (2005). Both the establishment and the maintenance of neuronal polarity require active mechanisms: critical roles of GSK-3band its upstream regulators.Cell120:123-135.

1-21）神经细胞迁移的方向性改变依赖突起的对调节其形成和选择(神经细胞运动)

Ward ME, Jiang H and Rao Y (2005). Regulated formation and selection of neuronal processes underlie directional guidance of neuronal migration.Mol Cell Neurosci30:378-387.

1-22）Netrin作用的下游需要的一个分子(基因、神经细胞)

Liu G, Li W, Gao X, Li X, Jurgensen C, Park HT, Shin NY, Yu J, He ML, Hanks SK, Wu JY and Rao Y(2007).p130(CAS) is required for netrin signaling and commissural axon guidance.J Neurosci27:957-68.

1-23）ILK蛋白激酶参与神经细胞极性形成(基因、神经细胞)

Guo W, Jiang H, Gray V, Dedhar S and Rao Y (2007).Role of the integrin-linked kinase (ILK) in determining neuronal polarity.Dev Biol306:457-468.

1-24）导向分子netrin下游需要鸟苷酸交换因子起吸引作用(基因、神经细胞)

Li X, Gao X, Liu G, Xiong W, Wu J and Rao Y (2008). Netrin signal transduction and the guanine nucleotide exchange factor DOCK180 in attractive signaling.Nat Neurosci11:28-35.

2）行为的分子机理

2-1）果蝇打架需要一群鱆胺能神经元(基因、行为)

Zhou C, Rao Y and Rao Y (2008). A subset of octopaminergic neurons are important for Drosophila aggression.Nat Neurosci11:1059-1067.

2-2）雄鼠性偏好需要脑内五羟色胺(基因、行为)

Liu Y, Jiang Y, Si Y, Kim J-Y, Chen Z-F and Rao Y (2011).Molecularregulation ofsexualpreferencerevealed bygeneticstudies of 5-HT in thebrain ofmalemice.Nature472:95-99.

2-3）果蝇嗅觉与打架需要的受体(基因、行为)

Liu WW, Liang XH, Li YN, Gong JX, Yang Z, Zhang YH, Zhang JX and Rao Y (2011). Social regulation of aggressionmediated by pheromonalactivation of Or65aolfactoryreceptorneurons in Drosophila.Nat Neurosci7:896-902.

2-4）果蝇求偶所需分子(基因、行为)

ZhouC, HuangH, KimSM, LinH, MengX, ChiangA-S, WangJW, Jiao R and Rao Y (2012) Molecular genetic analysis of sexual rejection: roles of octopamine and its receptor OAMB in Drosophila courtship conditioning.J Neurosci32:14281-14287.

2-5）雌鼠性偏好需要脑内五羟色胺(基因、行为)

Zhang SS, Liu Y and Rao Y (2013). Serotonin signaling in the brain of adult female mice is required for sexual preference.Proc Natl Acad Sci110:9968-9973.

2-6）五羟色胺参与小鼠、大鼠、猴的第一社会行为(基因、行为)

Liu Y, Shan L, Liu T, Li J, Chen YC, Sun CH, Yang CJ, Bian XL, Niu YY, Zhang C, Xi JZ and Rao Y (2023) Molecular and cellular mechanisms of the first social relationship: a conserved role of 5-HT from mice to monkeys, upstream of oxytocin.Neuron111:1468-1685.

3）人类认知

3-1）人类记忆激活的干扰(认知)

Zhu ZJ, Wang YY, Cao ZJ, Chen BQ, Cai HQ, Wu YH and Rao Y (2016). Cue-independent memory impairment by reactivation-coupled interference in human declarative memory.Cognition155:125-134.

3-2）人类从众行为的基因分析(基因、认知)

Chen BQ, Zhu, ZJ, WangYY, DingXH,GuoXB, He MG,FangW, ZhouSB, ZhouQ,HuangAL, ChenTM,NiDS, GuYP, LiuJN, Lei H and RaoY (2018). Nature vs. nurture in human sociality: multi-level genomic analyses of social conformity.J Hum Genet63:605-619.

3-3）人类记忆的基因分析(基因、认知)

Zhu ZJ, Chen BQ, Yan HM, Fang W, Zhou Q, Zhou SB, Lei H, Huang AL, Chen TM, Gao TM, Chen L, Chen JY, Ni DS, Gu YP, Liu JN, Zhang WX and Rao Y (2018). Multi-level genomic analyses suggest new genetic variants involved in human memory.Eur J Hum Genet26:1668-1678.

3-4）人类视觉认知的基因分析(基因、认知)

Chen BQ, Zhu ZJ, Na R, Fang W, Zhang WX, Zhou Q, Zhou SB, Lei H, Huang AL, Chen TM, Ni DS, Gu YP, Liu JN, Fang F and Rao Y (2018). Genomic analyses of visual cognition: perceptual rivalry and top-down control.J Neurosci38:9668-9678.

3-5）人类视觉整合的基因分析(基因、认知)

Zhu ZJ, Chen BQ, Na R, Fang W, Zhang WX, Zhou Q, Zhou SB, Lei H, Huang AL, Chen TM, Gao TM, Chen L, Ni DS, Gu YP, Liu JN, Chen JY, Rao Y and Fang F (2020). Heritability of human visual contour integration—an integrated genomic study.Eur J Hum Genet27:1867-1875.

3-6）人类视错觉的基因分析(基因、认知)

Zhu ZJ, Chen BQ, Na R, Fang W, Zhang WX, Zhou Q, Zhou SB, Lei H, Huang AL, Chen TM, Ni DS, Gu YP, Liu JN, Rao Y and Fang F (2020). A genome-wide association study reveals a substantial genetic basis underlying the Ebbinghaus illusion.J Hum Genet66:261-271.

3-7）人类脸识别的基因分析(基因、认知)

Sun Y, Men W, Fang W, Zhou E, Yang W, Li Z, Zheng H-F and Rao Y (2024). Human genetics of face recognition: discovery ofMCTP2mutations in humans with face blindness (congenital prosopagnosia).Genetics227:iyae047 (medRxiv2021.09.27.21263237).

4）睡眠的分子机理

4-1）果蝇5-HT受体控制睡眠(基因、睡眠)

Qian YJ, Cao Y, Deng BW, Yang G, Li J, Xu R, Zhang D, Huang J and Rao Y (2017). Sleep homeostasis regulated by 5HT2b receptor in a small subset of neurons in the dorsal fan-shaped body of Drosophila.eLife6:e26519.

4-2）小鼠5-HT调控睡眠(基因、睡眠)

Zhang X, Yan HM, Huang ZL and Rao Y (2018). Independence of 5HT involvement in sleep and arousal from thermoregulation in mice.Mol Pharmacol93:657-664.

4-3）果蝇肠上皮分泌D型丝氨酸通过神经细胞控制睡眠(基因、睡眠)

Dai XHM, Zhou EX, Yang W, WX Zhang and Rao Y (2019)D-Serine promotes sleep through the NMDA receptor in Drosophila melanogaster.Nat Comm10:1986.

4-4）果蝇乙酰胆碱通过不同受体对睡眠进行双向(基因、睡眠)

Dai XHM, Zhou EX, Yang W, Deng BW, Li Q, Liu XX, Zhang WX and Rao Y (2021). Molecular resolution of a behavioral paradox: sleep and arousal are regulated by distinct acetylcholine receptors in different neurons of Drosophila.Sleep10:zsab017.

4-5）蛋白激酶LKB1调节果蝇和小鼠睡眠(基因、睡眠)

Liu ZY, Jiang LF, Li CY, Li CG, Yang JQ, Yu JJ, Mao RB and Rao Y (2022). LKB1 is physiologically required for sleep fromDrosophila melanogastertoMus musculus.Genetics221: iyac082.

4-6）蛋白激酶SIK3的特定位点磷酸化调节小鼠睡眠(基因、睡眠)

Li Y, Li CG, Liu YX,Yu JJ, Yang JQ, Cui YF, Wang TV,Li CY,Jiang LF, Song MLand Rao Y(2023). Sleep need, the key regulator of sleep homeostasis, is both indicated and controlled by phosphorylation of threonine 221 in salt inducible kinase 3.Genetics224:iyad136(bioRxiv2021.11.06.467421).

4-7）新的小分子调节果蝇睡眠(遗传分子、睡眠)

Dai X, Yang W, Zhang X, Zhou E, Liu Y, Wang T, Zhang WX, Zhang XX and Rao Y (2023). ppGpp is present in, and functions to regulate sleep of, Drosophila.hLife1:98-114 (bioRxiv2022.11.17.516975).

4-8）生化发现的蛋白磷酸酶调节小鼠睡眠(生化、基因、睡眠)

Yu J, Wang TV, Gao R, Li CG, Liu HJ, Yang L, Liu YX, Cui YF, Chen RP and Rao Y (2025). Calcineurin: an essential regulator of sleep revealed bybiochemical, chemical biological, and genetic approaches.Cell Chem Biol32:1-17 (bioRxiv2023.06.19.545643).

4-9）蛋白激酶调节小鼠睡眠(基因、睡眠)

Yang WW, Shi JY, Li CG,Yang JQ, Yu JJ, Huang J and RaoY (2025).Ca2+/calmodulin-dependent kinase II a and b differentially regulate mammalian sleep.Comms Biol8:11 (bioRxiv2024.11.17.624045).

5）神经的化学连接

5-1）化学连接组概念和工具(基因、睡眠)

Deng BW, Li Q, Liu XX, Cao Y, Li BF, Qian YJ, Xu R, Mao RB, Zhou EX, Zhang WX, Huang J and Rao Y (2019) Chemoconnectomics: mapping chemical transmission in Drosophila.Neuron101:876-893.

5-2）条件型化学连接组工具(基因、睡眠)

Mao R, Yu J, Deng B, Dai X, Du Y, Du S, Zhang WX and Rao Y (2023). Conditional chemoconnectomics (cCCTomics) as a strategy for efficient and conditional targeting of chemical transmission.eLife12:RP91927 (bioRxiv2023.09.26.559642).

5-3）神经递质的寻找(生物化学、化学分析、导致人类痴呆基因突变的分子机理)

Jia X, Zhu J, Bian X, Liu S, Yu S, Liang W, Jiang L, Mao R and Rao Y (2023) Importance of glutamine in synaptic vesicles revealed by functional studies of SLC6A17 and its mutations pathogenic for intellectual disability.eLife12:RP86972(bioRxiv2022.10.25.513688).

5-4）神经递质的寻找(化学分析、生物化学、电生理)

Bian XL, Zhu JM, XB, Liang WJ, Yu SH and Rao Y (2023).Suggestion of creatine as a new neurotransmitter by approaches ranging from chemical analysis and biochemistry to electrophysiology.eLife12:RP89317 (bioRxiv2022.12.22.521565).

6）GPCP的新配体与功能

6-1）GPR39的新配体胆酸及其在急性胰腺炎的作用(分子生物学、成像、炎症模型)

Zi ZT and Rao Y (2024). Discoveries of GPR39 as an evolutionarily conserved receptor for bile acids and of its involvement in biliary acute pancreatitis.Sci Adv10:eadj0146.

7）生物化学分离纯化

7-1）AMPK蛋白激酶的上游激酶(生物化学、酶学分析)

Liu YX, Wang TV, Cui YF, Gao SX and Rao Y (2022). Biochemical purification uncovers mammalian sterile 3 (MST3) as a new protein kinase for multifunctional protein kinases AMPK and SIK3.J Biol Chem298:101929.

Liu YX, Wang TV, Cui YF, Li CY, Jiang LF and Rao Y (2022). STE20 phosphorylation of AMPK related kinases revealed by biochemical purifications combined with genetics.J Biol Chem298:101928.

8）分子探针

8-1）细胞骨架重组过程中N-WASP活性变化的时空显示(非功能研究)

Ward ME, Wu JY and Rao Y (2004). Visualization of spatially and temporally regulated N-WASP activity during cytoskeletal reorganization in living cells.Proc Natl Acad Sci101:970-974.

Wang C, Zhang X, Mao HY, Xian Y and Rao Y (2025). Development of a genetically encoded sensor for intracellular arginine.ACS Sensors10.1021.