Schwarting Gerald A, Henion Timothy R
Shriver Center, Waltham, Massachusetts 02452, USA.
Dev Neurobiol. 2007 Oct;67(12):1627-40. doi: 10.1002/dneu.20536.
During embryonic development, olfactory sensory neurons extend axons that form synapses with the dendrites of projection neurons in glomeruli of the olfactory bulb (OB). The glycosyltransferase beta3GnT1 regulates the expression of 1B2-reactive lactosamine glycans that are mosaically distributed among glomeruli. In newborn beta3GnT1-/- mice, lactosamine expression is lost, and many glomeruli fail to form. To determine the role of lactosamine in OB targeting, we analyzed the trajectories of specific OR axon populations and their reactivity with 1B2 in beta3GnT1-/- mice. mI7 axons and P2 axons, both of which are weakly 1B2+ in wild-type mice, fail to grow to their normal positions in the glomerular layer during early postnatal development and never recover in adult mutant mice. In contrast, many M72 axons, which are always lactosamine negative in wild-type mice, survive but are misguided to the extreme anterior OB in neonatal mutant mice and persist as heterotypic glomeruli, even in adult null mice. These results show that the loss of lactosamine differentially affects each OR population. Those that lose their normal expression of lactosamine fail to form stable connections with mitral and tufted cells in the OB, disappear during early postnatal development, and do not recover in adults. Neurons that are normally lactosamine negative, survive early postnatal degeneration in beta3GnT1-/- mice but extend axons that converge on inappropriate targets in the mutant OB.
在胚胎发育过程中，嗅觉感觉神经元会延伸轴突，这些轴突会与嗅球（OB）肾小球中的投射神经元的树突形成突触。糖基转移酶β3GnT1调节1B2反应性乳糖胺聚糖的表达，这些聚糖以镶嵌的方式分布在肾小球之间。在新生的β3GnT1基因敲除小鼠中，乳糖胺表达缺失，许多肾小球无法形成。为了确定乳糖胺在OB靶向中的作用，我们分析了β3GnT1基因敲除小鼠中特定嗅觉受体（OR）轴突群体的轨迹及其与1B2的反应性。mI7轴突和P2轴突在野生型小鼠中均为弱1B2阳性，在出生后早期发育过程中无法生长到肾小球层的正常位置，并且在成年突变小鼠中也无法恢复。相比之下，许多M72轴突在野生型小鼠中始终为乳糖胺阴性，但能够存活下来，但在新生突变小鼠中被误导到OB的最前端，并以异型肾小球的形式持续存在，即使在成年基因敲除小鼠中也是如此。这些结果表明，乳糖胺的缺失对每个OR群体有不同的影响。那些失去乳糖胺正常表达的群体无法与OB中的二尖瓣细胞和簇状细胞形成稳定连接，在出生后早期发育过程中消失，并且在成年后也无法恢复。那些通常为乳糖胺阴性的神经元在β3GnT1基因敲除小鼠的出生后早期退化中存活下来，但延伸的轴突会汇聚到突变OB中的不适当靶点上。
