Kay J N, Hannigan P, Kelley D B
Department of Biological Sciences, 911 Fairchild Building, Columbia University, New York, New York 10027, USA.
J Neurobiol. 1999 Sep 5;40(3):375-85.
In Xenopus laevis, the laryngeal motor nucleus (n. of cranial nerves IX-X) is part of a sexually differentiated, androgen sensitive neuromuscular system devoted to vocalization. Adult males have more n. IX-X neurons than females; however, during development of n. IX-X, the rate of neurogenesis does not appear to differ between the sexes. In this study, we explored the role of naturally occurring cell death in the development of this nucleus and asked whether cell death might be involved in establishing the sex difference in neuron number. Counts of n. IX-X neurons reveal that at tadpole stage 56, males and females have similar numbers of n. IX-X neurons, but by stage 64 male neuron numbers are greater. This sex difference arises owing to a greater net loss of neurons in females-males lose approximately 25% of their n. IX-X neurons between stages 56 and 64, while females lose approximately 47%. Sexual differentiation of n. IX-X neuron number coincides with a period of developmental cell death, as evidenced by terminal transferase-mediated dUTP nick-end labeling and the presence of pyknotic nuclei in n. IX-X. A role for gonadal hormones in controlling cell number was examined by treating tadpoles with exogenous androgen and determining the number of n. IX-X neurons at stage 64. Dihydrotestosterone (DHT) treatment from the beginning of the cell death period (stage 54) until stage 64 had no effect on the number of n. IX-X neurons in males but did significantly increase n. IX-X neuron number in females. This increase was sufficient to abolish the sex difference normally observed at stage 64. Although DHT induced increases in female neuron number, it did not induce increases in cell proliferation or addition of newly born neurons to n. IX-X. DHT may therefore have increased neuron number by protecting cells from death. We conclude that androgens can influence the survival of n. IX-X neurons during a period of naturally occurring cell death, and that this action of androgen is critical to the development of sex differences in n. IX-X neuron number.
在非洲爪蟾中，喉运动核（第IX - X对脑神经核）是一个性别分化、对雄激素敏感的神经肌肉系统的一部分，该系统专门用于发声。成年雄性的第IX - X对脑神经核神经元比雌性多；然而，在第IX - X对脑神经核的发育过程中，神经发生的速率在两性之间似乎没有差异。在本研究中，我们探讨了自然发生的细胞死亡在该核发育中的作用，并询问细胞死亡是否可能参与建立神经元数量的性别差异。对第IX - X对脑神经核神经元的计数显示，在蝌蚪第56阶段，雄性和雌性的第IX - X对脑神经核神经元数量相似，但到第64阶段，雄性的神经元数量更多。这种性别差异是由于雌性神经元的净损失更大——雄性在第56阶段和第64阶段之间损失了约25%的第IX - X对脑神经核神经元，而雌性损失了约47%。第IX - X对脑神经核神经元数量的性别分化与发育性细胞死亡时期相吻合，这通过末端转移酶介导的dUTP缺口末端标记以及第IX - X对脑神经核中固缩核的存在得以证明。通过用外源性雄激素处理蝌蚪并确定第64阶段第IX - X对脑神经核神经元的数量，研究了性腺激素在控制细胞数量中的作用。从细胞死亡期开始（第54阶段）到第64阶段用双氢睾酮（DHT）处理，对雄性第IX - X对脑神经核神经元的数量没有影响，但显著增加了雌性第IX - X对脑神经核神经元的数量。这种增加足以消除通常在第64阶段观察到的性别差异。尽管DHT诱导雌性神经元数量增加，但它并没有诱导细胞增殖增加或向第IX - X对脑神经核添加新生神经元。因此，DHT可能通过保护细胞免于死亡而增加了神经元数量。我们得出结论，雄激素可以在自然发生的细胞死亡期间影响第IX - X对脑神经核神经元的存活，并且雄激素的这种作用对于第IX - X对脑神经核神经元数量的性别差异发育至关重要。
