Moreno-Bravo Juan A, Martinez-Lopez Jesus E, Madrigal M Pilar, Kim Minkyung, Mastick Grant S, Lopez-Bendito Guillermina, Martinez Salvador, Puelles Eduardo
Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'Alacant, 03550, Alicante, Spain.
Department of Biology, University of Nevada, Reno, NV, 89557, USA.
Brain Struct Funct. 2016 Jan;221(1):665-78. doi: 10.1007/s00429-014-0932-4. Epub 2014 Nov 4.
The retroflex tract contains medial habenula efferents that target the hindbrain interpeduncular complex and surrounding areas. This tract displays a singular course. Initially, habenular axons extend ventralwards in front of the pretectum until they reach the basal plate. Next, they avoid crossing the local floor plate, sharply changing course caudalwards (the retroflexion alluded by the tract name) and navigate strictly antero-posteriorly across basal pretectum, midbrain and isthmus. Once they reach rhombomere 1, the habenular axons criss-cross the floor plate several times within the interpeduncular nuclear complex as they innervate it. Here we described the timing and details of growth phenomena as these axons navigate to their target. The first dorsoventral course apparently obeys Ntn1 attraction. We checked the role of local floor plate signaling in the decision to avoid the thalamic floor plate and bend caudalwards. Analyzing the altered floor and basal plates of Gli2 knockout mice, we found a contralateral projection of most habenular axons, plus ulterior bizarre navigation rostralwards. This crossing phenotype was due to a reduced expression of Slit repulsive cues, suggesting involvement of the floor-derived Robo-Slit system in the normal guidance of this tract. Using Slit and Robo mutant mice, open neural tube and co-culture assays, we determined that Robo1-Slit2 interaction is specifically required for impeding that medial habenular axons cross the thalamic floor plate. This pathfinding mechanism is essential to establish the functionally important habenulo-interpeduncular connection.
后屈束包含内侧缰核传出纤维，其靶向后脑脚间复合体及周围区域。该束呈现出独特的走行。起初，缰核轴突在前顶盖前方腹侧延伸，直至到达基板。接着，它们避开穿过局部底板，急剧改变方向向尾侧（该束名称所暗示的后屈），并严格地在基底前顶盖、中脑和峡部前后穿行。一旦到达菱脑节1，缰核轴突在支配脚间核复合体时会在其中多次交叉穿过底板。在此，我们描述了这些轴突向其靶标导航时生长现象的时间和细节。最初的背腹向走行显然遵循Ntn1的吸引作用。我们检查了局部底板信号在避免穿过丘脑底板并向尾侧弯曲这一决定中的作用。通过分析Gli2基因敲除小鼠改变的底板和基板，我们发现大多数缰核轴突出现对侧投射，以及随后向头侧的奇异导航。这种交叉表型是由于Slit排斥信号的表达减少，提示底板来源的Robo - Slit系统参与了该束的正常导向。使用Slit和Robo突变小鼠、开放神经管和共培养实验，我们确定Robo1 - Slit2相互作用对于阻止内侧缰核轴突穿过丘脑底板是特别必需的。这种寻路机制对于建立功能上重要的缰核 - 脚间连接至关重要。
