Fetal and postnatal neocortical development in a non-domesticated precocial ungulate, the European Wild Boar (Sus scrofa, LINNAEUS 1785)

目前哺乳动物早期新皮质发育的概念很大程度上是基于在其他出生的物种中获得的数据，如小型啮齿类动物(小鼠、大鼠)、更罕见的食肉动物(猫、雪貂)和灵长类动物(猴子、人)。几乎没有关于早熟和天生具有接近成熟的感觉和运动能力的有蹄类动物的信息。此外，实验室的啮齿动物品系是高度近亲繁殖的，不再是野生型。在这里，我们建议分析猪的胎儿和出生后新皮质的发育。猪是心脏、免疫学、皮肤、癌症转化研究的新兴模型，同时也是许多人类神经退行性和代谢性疾病的转化研究模型。这与猪脑细胞和神经化学水平的知识出人意料地少形成了鲜明对比。从自己发表的初步研究和正在进行的工作中，我们已经了解到，许多自然出生的啮齿动物和食肉动物在出生后发生的许多过程，如睁眼，在猪的胎儿期就已经开始了。我们对从皮质板形成期(E35，公猪妊娠114d)到出生后各阶段的早期脑发育提出了全面和全面的分析：1)用免疫组织化学标记增殖细胞、板下神经元、皮质板层、Cajal-Retzius细胞和边缘带/层的中间神经元；2)皮质板内抑制的中间神经元类型和锥体细胞成熟，重点是轴体和轴轴神经支配；3)板层内神经胶质、髓鞘、小胶质细胞和血管的发育；4)用Western印迹分析突触前和突触后蛋白的表达，目的是将猪的“突触年龄”与啮齿动物、食肉动物和人类相一致；5)考虑与视觉和躯体感觉皮质可塑性关键期的开始和结束相关的蛋白质和凝集素。该项目将使用来自欧洲野猪Sus scrofa(Linneeus 1785)的材料完成，这是一种非家养动物。我们的共同目标是将有蹄类大脑发育引入皮质发生领域，并推广其他可能比同脑小型啮齿动物更接近人类的皮质发育模型。最终--从森林到实验室--我们觉得是时候探索神经生物学的新模型了。

The current concepts of early neocortical development in mammals are largely based on data obtained in altricially born species such as small rodents (mouse, rat), more rarely carnivores (cat, ferret), and primates (monkey, human). Almost no information is available on ungulates which are precocial and born with nearly mature sensory and motor abilities. Moreover, the laboratory rodent lines are highly inbred and no longer wildtype. Here we propose to analyze fetal and postnatal neocortical development of the pig. The pig is an emerging model for translational research into heart, immunology, skin, cancer, and – since transgenesis is established in pig – meanwhile for many human neurodegenerative and metabolic disorders. This contrasts with surprisingly little knowledge at the cellular and neurochemical level of pig brain. From own preliminary published and ongoing work we already learned that many processes which in altricially born rodent and carnivore occur after birth and concurr in time with e.g. eye opening, proceed already during the fetal period in pig. We propose a thorough and comprehensive analysis of the following aspects of early brain development starting from the stage of cortical plate formation (E35, gestation in boar is 114 days) and well into postnatal stages: 1) delineation and fate of embryonic and fetal laminar compartments using immunohistochemistry with markers for proliferating cells, subplate neurons, cortical plate layers, and the Cajal-Retzius cells and interneurons of the marginal zone/layer I; 2) maturation of the inhibitory interneuron types and pyramidal cells of the cortical plate with an emphasis on axosomatic and axoaxonic innervations; 3) development of neuroglia, myelination, microglia and blood vessels in the laminar compartments; 4) profiling the expression of pre- and postsynaptic proteins using Western blot, aiming at aligning "synaptic age" in pig to rodent, carnivore, and human; 5) considering proteins and lectins the expression of which has been reported to correlate with onset and closure of the critical period of cortical plasticity in visual and somatosensory cortex. The project will be done with material from European wild boar, Sus scrofa (LINNAEUS 1785), a non-domesticated animal. Together, our goal is to introduce ungulate brain development to the field of corticogenesis and to promote other models for cortex development which may be closer to human than lissencephalic small rodents. Ultimately - from the forest to the lab – we feel that is high time to explore novel models in neurobiology.