萬(wàn)麗丹，劉厚奇，丁文龍

（1南昌大學(xué)基礎(chǔ)醫(yī)學(xué)院人體解剖學(xué)教研室，南昌 330006；2第二軍醫(yī)大學(xué)組織胚胎學(xué)教研室，上海200433；3上海交通大學(xué)基礎(chǔ)醫(yī)學(xué)院解剖學(xué)教研室，上海 200025）

Schwann細(xì)胞在髓鞘形成過(guò)程中的極性調(diào)控

萬(wàn)麗丹1,3，劉厚奇2*，丁文龍3

（1南昌大學(xué)基礎(chǔ)醫(yī)學(xué)院人體解剖學(xué)教研室，南昌 330006；2第二軍醫(yī)大學(xué)組織胚胎學(xué)教研室，上海200433；3上海交通大學(xué)基礎(chǔ)醫(yī)學(xué)院解剖學(xué)教研室，上海 200025）

周圍神經(jīng)系統(tǒng)髓鞘形成依賴Schwann細(xì)胞和神經(jīng)元之間復(fù)雜的相互作用。細(xì)胞極性分子蛋白Par-3在Schwann細(xì)胞與軸突接觸面密集分布，為BDNF/p75NTR介導(dǎo)的啟動(dòng)成髓提供分子支架。然而，Par-3在該界面聚集并呈不對(duì)稱性分布的機(jī)制仍是一個(gè)謎。不少研究發(fā)現(xiàn)，JAM和nectin等細(xì)胞粘附分子與Par-3不對(duì)稱性分布有關(guān)。另外，通過(guò)改變軸突信號(hào)如神經(jīng)營(yíng)養(yǎng)因子和神經(jīng)素的水平，也能影響Schwann髓鞘的形成。本文綜述和闡釋在髓鞘形成過(guò)程中，Schwann細(xì)胞極性是如何被調(diào)控的。

Schwann細(xì)胞；髓鞘形成；細(xì)胞極性；Par-3

神經(jīng)膠質(zhì)細(xì)胞包繞神經(jīng)元軸突形成髓鞘，從而使郎飛結(jié)之間的軸突與外界絕緣，保證神經(jīng)沖動(dòng)快速跳躍式的傳導(dǎo)。髓鞘的形成是一個(gè)復(fù)雜的動(dòng)態(tài)的過(guò)程，神經(jīng)元和神經(jīng)膠質(zhì)細(xì)胞之間的精細(xì)調(diào)節(jié)控制著成髓鞘的各個(gè)階段。以周圍神經(jīng)系統(tǒng)為例，Schwann細(xì)胞的成髓過(guò)程包含3個(gè)階段：接受軸突信號(hào)后迅速增殖和向軸突遷移、沿軸突延長(zhǎng)和包裹軸突以及包繞軸突形成致密髓鞘。軸突信號(hào)對(duì)髓鞘的啟動(dòng)及維持至關(guān)重要，綜合調(diào)控Schwann細(xì)胞成髓的3類軸突信號(hào)主要有：神經(jīng)營(yíng)養(yǎng)因子[1,2]、神經(jīng)素[3,4]和神經(jīng)元自身電興奮性[5,6]。

1 Schwann細(xì)胞啟動(dòng)成髓時(shí)細(xì)胞極性的形成機(jī)制

髓鞘的形成有賴于神經(jīng)膠質(zhì)細(xì)胞中細(xì)胞器的兩極分化，這種高度極性化需要細(xì)胞極性蛋白(polarity complex proteins)的參與[7]，如partitioning-defective (Par) proteins[8]、Pals1[9]和Dlg1[10]。以partitioning-defective 3 (Par-3)為例，它分布于細(xì)胞膜、細(xì)胞核和細(xì)胞漿中[11]。位于Schwann細(xì)胞膜上的Par-3主要參與髓鞘施瑯切跡及結(jié)環(huán)處緊密連接的形成，結(jié)合其他連接蛋白保證大分子物質(zhì)在髓鞘內(nèi)的正常分布，避免髓鞘外環(huán)境對(duì)髓鞘內(nèi)部的干擾，維持著髓鞘內(nèi)環(huán)境的穩(wěn)定，確保髓鞘的絕緣性以及神經(jīng)沖動(dòng)正確有序的傳導(dǎo)[12]。Chan等人[8]研究發(fā)現(xiàn)在啟動(dòng)成髓時(shí)，Schwann細(xì)胞中的Par-3局限分布在與軸突接觸一側(cè)胞膜的亞細(xì)胞區(qū)域，其膜表面p75NTR也匯聚于此，膜內(nèi)部分借PDZ結(jié)構(gòu)域與Par-3結(jié)合形成p75NTRPar-3復(fù)合體，膜外部分則結(jié)合BDNF。他們進(jìn)一步研究發(fā)現(xiàn)，Schwann細(xì)胞內(nèi)Rac1也被限制到該處激活，而敲除Par-3基因會(huì)抑制Rac1在正確位點(diǎn)的激活[13]。由此看來(lái)，分布于Schwann細(xì)胞中的Par-3就像一個(gè)分子支架，可以將形成髓鞘所需的關(guān)鍵蛋白召集起來(lái)，介導(dǎo)BDNF對(duì)髓鞘形成的啟動(dòng)。進(jìn)一步研究又發(fā)現(xiàn)[14]，與Par-3共定位于Schwann細(xì)胞膜下區(qū)域的LKB1復(fù)合物通過(guò)調(diào)控Par-3的分布影響著Schwann細(xì)胞極性的建立和髓鞘的形成，首先，LKB1本身的定位有賴于PKA在ser-431位點(diǎn)的磷酸化，然后與Par-3形成復(fù)合物并聚集于Schwann細(xì)胞膜下，同時(shí)與膜表面的p75NTR形成復(fù)合物介導(dǎo)BDNF對(duì)髓鞘形成的啟動(dòng)，后續(xù)Pals1[9]和Dlg1[10]調(diào)整髓鞘厚度，而LKB1就在這多種信號(hào)通路中發(fā)揮整合作用。這一以細(xì)胞極性Par蛋白為核心的供應(yīng)鏈通過(guò)協(xié)調(diào)和分配胞內(nèi)多個(gè)信號(hào)復(fù)合物，對(duì)Schwann細(xì)胞啟動(dòng)和控制髓鞘形成發(fā)揮重要作用（圖1）。反過(guò)來(lái)說(shuō)，Schwann細(xì)胞首先必須形成極性，才能判斷細(xì)胞的哪一側(cè)和軸突接觸了，而Par蛋白尤其是Par-3就是Schwann細(xì)胞極性化的分子基礎(chǔ)，同時(shí)還承擔(dān)著募集膜表面受體和某些胞內(nèi)信號(hào)的任務(wù)。當(dāng)這個(gè)由Par-3參與形成的分子支架被打亂后，細(xì)胞就不能啟動(dòng)成髓，也無(wú)法形成正常的髓鞘。

2 細(xì)胞粘附分子在Schwann細(xì)胞形成極性中的作用

雖然已知Par-3是Schwann細(xì)胞極性化的分子基礎(chǔ)，然而，Par-3本身是被什么力量牽引到Schwann細(xì)胞與軸突接觸這一側(cè)的尚不清楚。Jonah R Chan等發(fā)現(xiàn)[8]，單個(gè)孤立的Schwann細(xì)胞中Par-3呈彌散分布，而與其他Schwann細(xì)胞或神經(jīng)元軸突接觸后才呈極性分布。這一現(xiàn)象說(shuō)明與細(xì)胞連接有關(guān)的物質(zhì)參與了Par-3的極性分布，例如細(xì)胞粘附分子。當(dāng)Schwann細(xì)胞與軸突接觸時(shí)，N-cadherin與Par-3的這種極性分布保持一致[8,15]。進(jìn)一步研究發(fā)現(xiàn)，體外敲除Schwann細(xì)胞而不是神經(jīng)元N-cadherin基因會(huì)破壞Par-3的分布，延遲啟動(dòng)成髓；敲除N-cadherin基因的小鼠只表現(xiàn)出輕度延遲和輕微的髓鞘缺損，消除N-cadherin下游效應(yīng)器β-Catenin基因的小鼠則表現(xiàn)出更嚴(yán)重的啟動(dòng)成髓遲緩，但沒(méi)有任何髓鞘缺損[15]。這說(shuō)明N-cadherin和β-catenin在Schwann細(xì)胞極性化和啟動(dòng)成髓發(fā)揮重要作用，對(duì)髓鞘的成熟則不是必須的。另有學(xué)者發(fā)現(xiàn)，分布于Schwann細(xì)胞中的粘附分子junctional adhesion molecule (JAM)-C對(duì)維持髓鞘的完整性和功能也發(fā)揮重要作用[16]，但這份研究并沒(méi)有明確指出JAM-C在啟動(dòng)成髓時(shí)扮演何種角色。不過(guò)，人們?cè)趯?duì)上皮細(xì)胞極性化的研究中觀察到在形成細(xì)胞連接的過(guò)程中，細(xì)胞間需先形成不成熟的原始黏附物(primordial adgesiuons, PAs)，在此基礎(chǔ)上，JAM率先集中到PAs處，并開(kāi)始募集內(nèi)源性Par-3[17]，而且在眾多與緊密連接相關(guān)的免疫球蛋白樣穿膜蛋白中Par-3僅選擇性的與JAM家族結(jié)合[18]。Par-3在被JAM募集到PAs處后，作為絞手架分子，第一個(gè)PDZ結(jié)構(gòu)域與Par-6結(jié)合，再通過(guò)atypical protein kinase C (aPKC)結(jié)合域與aPKC結(jié)合形成三元復(fù)合物，aPKC還能以Par-3依賴性的方式磷酸化JAM，以此來(lái)調(diào)整細(xì)胞間連接的成熟程度[19]。Par-3和Par-6都擁有PDZ結(jié)構(gòu)，它們可以在胞膜的亞細(xì)胞區(qū)域作為合成蛋白復(fù)合物的支架蛋白[20]。研究發(fā)現(xiàn)，Schwann細(xì)胞高表達(dá)Par-6也會(huì)破壞Par-3極性分布，最終表現(xiàn)為抑制髓鞘的形成[8]。Sir-two-homolog 2 (Sirt2)可通過(guò)操縱Par-3乙酰化來(lái)調(diào)整aPKC的活化狀態(tài)，進(jìn)而影響髓鞘的形成過(guò)程[21]。事實(shí)上，這些蛋白之間的相互作用非常復(fù)雜，作為Par-3的募集者JAM本身在細(xì)胞特定區(qū)域的極性分布也受其他分子如Nectin調(diào)節(jié)[22]。除此之外，某些細(xì)胞內(nèi)信號(hào)分子如phosphatidylinositol 3 kinase (PⅠ3K)可能影響Par-3在PAs中的定位，這可能與PⅠ3K可調(diào)控Cdc42的激活，影響Cdc42與Par-6的結(jié)合而引起下游效應(yīng)有關(guān)[23]。然而，關(guān)于Schwann細(xì)胞中Par-3是否能與JAM結(jié)合并被其募集至Schwann細(xì)胞與軸突接觸面的胞膜下區(qū)域，以及細(xì)胞粘附分子家族其他成員和胞內(nèi)信號(hào)分子是否也參與了Par-3的極性分布尚不清楚。

3 神經(jīng)營(yíng)養(yǎng)因子BDNF參與調(diào)控Schwann細(xì)胞極性化

圖1 Schwann細(xì)胞在髓鞘形成過(guò)程中的極性化及胞內(nèi)信號(hào)通路示意圖Fig. 1 A schematic illustration of the intracellular signaling for the Schwann cell polarization during myelin formation. Par-3, partitioning-defective 3; LKB1, liver kinase B1; PKA, protein kinase A; BDNF, brain-derived neurotrophic factor; TrkB-T1, truncated tropomyosin receptor kinase B; p75NTR, p75 nerve growth factor receptor; NT-3, neurotrophin-3; TrkC, tropomyosin receptor kinase C; GEF, guanine nucleotide exchange factor; Tiam, T-lymphom invasion and metastasis; Dbs, Dbl’s big sister; Cdc42, cell division control protein 42; JNK, jun N-terminal kinase; NGF, nerve growth factor; TrkA, tropomyosin receptor kinase A; GDNF, glial cell-derived neurotrophic factor; NRG-1, neuregulin-1; ErbB2/3, epidermal growth factor receptor2/3; PⅠP3, phosphatidylinositol (3,4,5)-trisphosphate; Akt, protein kinase B; FAK, focal adhesion kinase; JAM, junctional adhesion molecule; LⅠNGO-1, immunoglobin-like domain-containing protein 1

在DRG神經(jīng)元與Schwann細(xì)胞共培養(yǎng)體系中加入外源性BDNF會(huì)增強(qiáng)p75NTR與Par-3的結(jié)合，而去除內(nèi)源性BDNF會(huì)削弱兩者結(jié)合，這一結(jié)果表明p75NTR與Par-3的結(jié)合受BDNF調(diào)節(jié)，是供體依賴性的[8]。簡(jiǎn)單來(lái)說(shuō)，Par-3在哪，p75NTR就往哪遷移，但是被Par-3集結(jié)的p75NTR的數(shù)量多少與胞外BDNF濃度高低有關(guān)?；蛘呖梢岳斫鉃?，Par-3定向分布于Schwann細(xì)胞與軸突接觸面，本來(lái)就是為募集p75NTR于此以便接收胞外BDNF信號(hào)用的，但是在沒(méi)有或者缺少足夠的BDNF結(jié)合p75NTR的情況下，Par-3這種極性分布也是徒勞無(wú)功，甚至還可能導(dǎo)致Schwann細(xì)胞錯(cuò)誤地認(rèn)為軸突不需要成髓鞘或啟動(dòng)成髓鞘已經(jīng)完成，而將Par-3和p75NTR撤退。由于BDNF和Par-3都是在啟動(dòng)成髓時(shí)達(dá)峰值，在啟動(dòng)成髓前和完成啟動(dòng)成髓后，Par-3表達(dá)量很少甚至沒(méi)有，而去除內(nèi)源性BDNF導(dǎo)致p75NTR和Par-3的結(jié)合減少，似乎BDNF是根據(jù)自己的需要上調(diào)Par-3表達(dá)為其服務(wù)。研究證實(shí)，通過(guò)增強(qiáng)DRG神經(jīng)元高表達(dá)內(nèi)源性BDNF，并沿軸漿順行運(yùn)輸和分泌，能促進(jìn)和加快Schwann細(xì)胞成髓鞘[24]，這種作用甚至能一直持續(xù)至動(dòng)物成年[25]。因此，自軸突部位釋放BDNF濃度升高對(duì)髓鞘形成的促進(jìn)作用原理之一可能是通過(guò)增強(qiáng)p75NTR-Par-3復(fù)合體的形成，最終加快成髓鞘的啟動(dòng)。這些結(jié)果提示啟動(dòng)成髓時(shí)，高濃度的BDNF正是上調(diào)Par-3表達(dá)的重要軸突信號(hào)。這說(shuō)明，軸突的存在和軸突信號(hào)都能通過(guò)調(diào)控Schwann細(xì)胞極性化影響其髓鞘形成過(guò)程。

我們?cè)源笫笞巧窠?jīng)擠壓傷模型為研究對(duì)象，檢測(cè)和觀察了損傷后髓鞘再生狀況是否與軸突和軸突信號(hào)對(duì)Schwann細(xì)胞極性化有關(guān)[26]。我們的研究發(fā)現(xiàn)，正常大鼠坐骨神經(jīng)中即有非常少量的Par-3表達(dá)，這一結(jié)果提示正常神經(jīng)組織中就存在非常少量的動(dòng)態(tài)的偶然的脫髓鞘現(xiàn)象，脫髓鞘后也可能自行再形成髓鞘。損傷后1周，Par-3開(kāi)始表達(dá)并不斷增強(qiáng)。至損傷后2～3周，Par-3達(dá)到峰值，損傷后4周和8周則逐漸降低，Beirowski等人的研究也得出類似的結(jié)果[21]。此外，Par-3在Schwann細(xì)胞中的分布也和以上結(jié)果趨于一致，損傷后1周，損傷遠(yuǎn)端經(jīng)歷Wallerian變性，大部分再生軸突尚未穿過(guò)損傷區(qū)域，損傷遠(yuǎn)端部位的絕大多數(shù)Schwann細(xì)胞還未與軸突接觸，這時(shí)絕大多數(shù)Schwann細(xì)胞內(nèi)不存在Par-3不對(duì)稱性分布，也就是說(shuō)它們還未極性化為包繞軸突做準(zhǔn)備。損傷后2周，大量再生軸突跨越損傷區(qū)域到達(dá)遠(yuǎn)端并與Schwann細(xì)胞接觸，從神經(jīng)橫斷面上觀察Schwann細(xì)胞內(nèi)Par-3呈新月形或C形分布，似與軸突接觸或包繞軸突。但是，盡管損傷后4周和8周再生軸突已長(zhǎng)入損傷遠(yuǎn)端，Par-3的這種不對(duì)稱性分布卻未觀察到。這說(shuō)明神經(jīng)損傷后，與軸突失去聯(lián)系對(duì)Schwann細(xì)胞來(lái)說(shuō)是一種上調(diào)Par-3表達(dá)同時(shí)調(diào)整其分布的強(qiáng)有力信號(hào)，當(dāng)Schwann細(xì)胞遷移至軸突附近準(zhǔn)備包繞軸突啟動(dòng)成髓時(shí)，Par-3會(huì)達(dá)到峰值并呈極性分布。筆者還檢測(cè)了神經(jīng)組織中BDNF的表達(dá)，損傷后1周BDNF為峰值水平，以后逐步減少，其表達(dá)規(guī)律并非與Par-3一一對(duì)應(yīng)，但是增強(qiáng)表達(dá)BDNF時(shí)髓鞘再生情況比單純損傷組更好，更接近于未損傷神經(jīng)[26]。結(jié)合以上研究工作，筆者初步推測(cè)，神經(jīng)損傷后通過(guò)增強(qiáng)神經(jīng)組織表達(dá)BDNF，可能能在Schwann細(xì)胞與軸突發(fā)生接觸時(shí)，促使Schwann細(xì)胞形成極性，從而加快啟動(dòng)成髓，促進(jìn)髓鞘再生。

4 Schwann細(xì)胞成髓鞘過(guò)程中的信號(hào)通路調(diào)控

在髓鞘形成過(guò)程中，不同神經(jīng)營(yíng)養(yǎng)因子對(duì)Schwann細(xì)胞發(fā)揮不同甚至截然相反的作用（圖1），如NT-3/TrkC則通過(guò)激活Rho GTPases Rac1和Cdc42以及下游信號(hào)c-Jun N-terminal kinase (c-JNK)，促進(jìn)Schwann細(xì)胞遷移，抑制其成髓[27-29]；BDNF/p75NTR通過(guò)Src kinase/Vav2/RhoA/Rho-kinase信號(hào)通路抑制Schwann細(xì)胞遷移，啟動(dòng)髓鞘的形成[30,31]。那么，在啟動(dòng)成髓前Schwann細(xì)胞沿軸突遷移階段，高濃度的NT-3對(duì)啟動(dòng)成髓的抑制是否包含了它對(duì)Par-3表達(dá)的不允許呢？以BDNF和NT-3為例，我們假設(shè)它們對(duì)Par-3表達(dá)的調(diào)控，正是經(jīng)由上述信號(hào)通路，也就是說(shuō)在啟動(dòng)成髓前，NT-3/TrkC通過(guò)激活Rac1和Cdc42以及c-JNK，抑制Par-3表達(dá)，阻止Schwann細(xì)胞極性化，保持其遷移狀態(tài)；在啟動(dòng)成髓時(shí)，BDNF/p75NTR通過(guò)Src kinase/Vav2/ RhoA/Rho-kinase，上調(diào)Par-3表達(dá)；分布于Schwann細(xì)胞與軸突接觸面的Par-3為BDNF募集大量p75NTR使它更高效地啟動(dòng)成髓。另外，NGF和GDNF通過(guò)分別結(jié)合神經(jīng)元表面TrkA和Ret受體，最終表現(xiàn)為促進(jìn)髓鞘形成[32,33]，其機(jī)制可能是兩者使神經(jīng)元高表達(dá)內(nèi)源性BDNF，間接上調(diào)Schwann細(xì)胞中Par-3的表達(dá)水平。除神經(jīng)營(yíng)養(yǎng)因子外，還有一種重要的軸突信號(hào)Neuregulin-1 (Nrg-1)通過(guò)Schwann細(xì)胞表面ErbB2/3受體，參與了其髓鞘形成的全部過(guò)程[4]以及神經(jīng)損傷后的髓鞘再生[34]，研究指出不同濃度Nrg-1 ⅠⅠⅠ和Nrg-1 ⅠⅠ對(duì)Schwann細(xì)胞成髓鞘效果不同[35]，低濃度Nrg-1 ⅠⅠ能引起了Schwann細(xì)胞沿軸突延長(zhǎng)和包裹軸突的效果。然而，高劑量Nrg-1 ⅠⅠⅠ和Nrg-1 ⅠⅠ則通過(guò)激活Mek/Erk上調(diào)c-JNK的表達(dá)抑制髓鞘形成。這些結(jié)果表明，旁分泌Nrg-1信號(hào)對(duì)Schwann細(xì)胞成髓鞘起濃度依賴性的雙重影響。但是Nrg-1/ErbB2/3及其下游信號(hào)通路是否參與調(diào)控Schwann細(xì)胞中Par-3的表達(dá)，目前還沒(méi)有研究報(bào)道。總之，BDNF、NT-3、NGF、GDNF、Nrg-1 ⅠⅠⅠ和Nrg-1 ⅠⅠ濃度的高低對(duì)Schwann細(xì)胞中Par-3表達(dá)有何影響，尚未開(kāi)始探討。調(diào)控Schwann細(xì)胞中Par-3合成的胞內(nèi)信號(hào)通路也不明了。有關(guān)BDNF/p75NTR、NT-3/TrkC、NGF/TrkA、GDNF/Ret、Nrg-1/ErbB2/3信號(hào)通路與Schwann細(xì)胞Par-3表達(dá)和在正確位點(diǎn)的極性分布之間的關(guān)系尚需進(jìn)一步研究探索。

5 結(jié)語(yǔ)

國(guó)內(nèi)外研究結(jié)果揭示出周圍神經(jīng)脫髓鞘后髓鞘形成不良的發(fā)生發(fā)展機(jī)制之一，可能與Schwann細(xì)胞極性化異常有關(guān)，那么哪些因素的出現(xiàn)將導(dǎo)致Schwann細(xì)胞極性化被打破或無(wú)法形成，以及如何修復(fù)呢？要探討這些問(wèn)題，我們認(rèn)為至少存在以下兩種情形（以p75NTR-Par-3支架為例）：一種是Schwann細(xì)胞中Par-3表達(dá)下調(diào)，這種情況主要由軸突是否存在和軸突信號(hào)是否失調(diào)所致。因此，上調(diào)Par-3表達(dá)的信號(hào)至少包含兩部分：Schwann細(xì)胞是否與軸突接觸、BDNF水平是否足夠；另一種是在Schwann細(xì)胞中Par-3和p75NTR均表達(dá)正常，Par-3沒(méi)有在與軸突接觸面出現(xiàn)極性分布，例如它不被JAM募集或者能影響它定位的某些胞內(nèi)信號(hào)失調(diào)，此時(shí)，下Par-3無(wú)法為BDNF募集p75NTR，BDNF就不能更快更有效的發(fā)揮啟動(dòng)成髓的作用了。值得注意的是，Par-3表達(dá)并非越高越好，事實(shí)上Par-3過(guò)度表達(dá)反而破壞了它在Schwann細(xì)胞中的極性分布，最終表現(xiàn)為抑制成髓[8]。不論是以上何種原因?qū)е翽ar-3支架瓦解，如果能通過(guò)某些途徑幫助Schwann細(xì)胞建立這個(gè)支架或更好的利用這個(gè)支架，或者使這個(gè)支架免于攻擊將對(duì)髓鞘再生起到積極的作用。

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Regulation of the polarization of Schwann cell during myelination

Wan Lidan1,3, Liu Houqi2*, Ding Wenlong3
(1Department of Anatomy , Basic medical school , Nanchang University, Nanchang 330006;2Department of Histology and Embryology, The Second Military Medical University , Shanghai 200433 ;3Department of Anatomy , School of Medicine , Shanghai Jiaotong University , Shanghai 200025, China)

The cellular events that preceding myelination in the peripheral nervous system is dependent on complex reciprocal interactions between Schwann cell (SC) and axon. The Par-3, as an intracellular scaffold, is enriched at SC-axon interface and functions for BDNF/p75NTRto promote myelination initiation. However, the mechanism of Par-3 recruitment and asymmetrical distribution at this polarized-apical domain remains a mystery. Many studies have found that junctional adhesion molecule(JAM) and Nectin and other cell adhesion molecules were related to the asymmetric distribution of Par-3 at SC-axon interface. Ⅰn addition, changes in axonal signaling, such as neurotrophic factor or neuregulin-1, can also contribute to the formation of Schwann myelin. The purpose of this paper is to summarize and explain how the polarity of Schwann cells is regulated during myelination.

Schwann cell; Myelination; Cell polarity; Par-3

R338.1+1

A DOⅠ：10.16705/ j. cnki. 1004-1850.2017.04.011

2017-02-10

2017-07-10

江西省自然科學(xué)基金（00014918）；南昌大學(xué)博士科研啟動(dòng)基金

萬(wàn)麗丹，女(1980年)，漢族，講師，博士

*通訊作者(To whom correspondence should be addressed)：houqiLiu@126.com