Seth Anandita, Culverwell James, Walkowicz Mitchell, Toro Sabrina, Rick Jens M, Neuhauss Stephan C F, Varga Zoltan M, Karlstrom Rolf O
Biology Department, University of Massachusetts, Amherst, MA 01003-9297, USA.
Development. 2006 Feb;133(4):725-35. doi: 10.1242/dev.02244.
Some of the earliest axon pathways to form in the vertebrate forebrain are established as commissural and retinal axons cross the midline of the diencephalon and telencephalon. To better understand axon guidance in the forebrain, we characterized the zebrafish belladonna (bel) mutation, which disrupts commissural and retinal axon guidance in the forebrain. Using a positional cloning strategy, we determined that the bel locus encodes zebrafish Lhx2, a lim-homeodomain transcription factor expressed in the brain, eye and fin buds. We show that bel(Ihx2) function is required for patterning in the ventral forebrain and eye, and that loss of bel function leads to alterations in regulatory gene expression, perturbations in axon guidance factors, and the absence of an optic chiasm and forebrain commissures. Our analysis reveals new roles for Ihx2 in midline axon guidance, forebrain patterning and eye morphogenesis.
脊椎动物前脑中最早形成的一些轴突通路是在连合轴突和视网膜轴突穿过间脑和端脑的中线时建立的。为了更好地理解前脑中的轴突导向，我们对斑马鱼颠茄（bel）突变进行了特征分析，该突变破坏了前脑中的连合轴突和视网膜轴突导向。使用定位克隆策略，我们确定bel基因座编码斑马鱼Lhx2，一种在脑、眼和鳍芽中表达的含LIM结构域的同源异型转录因子。我们表明，bel（Lhx2）功能对于腹侧前脑和眼睛的模式形成是必需的，并且bel功能的丧失会导致调节基因表达的改变、轴突导向因子的扰动，以及视交叉和前脑连合的缺失。我们的分析揭示了Ihx2在中线轴突导向、前脑模式形成和眼睛形态发生中的新作用。
