The nature versus nurture debate has recently resurfaced with the emergence of the field of developmental molecular neurobiology. The questions associated with "nature" have crystallized into testable hypotheses regarding patterns of gene expression during development, and those associated with "nurture" have given over to activity-dependent cellular mechanisms that give rise to variable phenotypes in developing nervous systems. This review focuses on some of the features associated with complex brains and discusses the evolutionary and activity-dependent mechanisms that generate these features. These include increases in the size of the cortical sheet, changes in cortical domain and cortical field specification, and the activity-dependent intracellular mechanisms that regulate the structure and function of neurons during development. We discuss which features are likely to be genetically mediated, which features are likely to be regulated by activity, and how these two mechanisms act in concert to produce the wide variety of phenotypes observed for the mammalian neocortex. For example, the size of the cortical sheet is likely to be under genetic control, and regulation of cell-cycle kinetics through upregulation of genes such as beta-catenin can account for increases in the size of the cortical sheet. Similarly, intrinsic signaling genes or gene products such as Wnt, Shh, Fgf2, Fgf8 and BMP may set up a combinatorial coordinate system that guides thalamic afferents. Changes in peripheral morphology that regulate patterned activity are also likely to be under genetic control. Finally, the intracellular machinery that allows for activity-dependent plasticity in the developing CNS may be genetically regulated, although the specific phenotype they generate are not. On the other hand, aspects of neocortical organization such as sensory domain assignment, the size and shape of cortical fields, some aspects of connectivity, and details of functional organization are likely to be activity-dependent. Furthermore, the role of genes versus activity, and their interactions, may be different for primary fields versus non-primary fields.

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重新审视自然与养育：一个古老的观念与新的转折。

随着发育分子神经生物学领域的出现，有关自然与养育的争论最近重新浮出水面。与“自然”相关的问题已经明确化为关于发育过程中基因表达模式的可检验假说，而与“营养”相关的问题则被赋予了活动依赖性细胞机制，该机制在发育中的神经系统中引起可变的表型。这篇综述着重于与复杂大脑相关的一些特征，并讨论了产生这些特征的进化和依赖于活动的机制。其中包括皮质板尺寸的增加，皮质区域和皮质视野规格的变化，以及在发育过程中调节神经元结构和功能的依赖活动的细胞内机制。我们讨论了哪些特征可能是由遗传介导的，哪些特征可能是由活性调节的，以及这两种机制如何协同作用以产生哺乳动物新皮层观察到的多种表型。例如，皮层片的大小很可能受到遗传控制，而通过上调基因（例如β-catenin）调节细胞周期动力学可以解释皮层片的大小增加。同样，内在的信号基因或基因产物（例如Wnt，Shh，Fgf2，Fgf8和BMP）可以建立引导丘脑传入的组合坐标系。调节模式活动的外周形态变化也可能受到遗传控制。最后，尽管在发育中的中枢神经系统中产生依赖于活动的可塑性的细胞内机制可以被遗传调控，尽管它们产生的具体表型却没有。另一方面，新皮层组织的各个方面（如感觉区域分配，皮层区域的大小和形状，连通性的某些方面以及功能组织的细节）可能与活动有关。此外，对于主场与非主场，基因相对于活性的作用及其相互作用可能不同。尽管它们产生的具体表型不是。另一方面，新皮层组织的各个方面（如感觉区域分配，皮层区域的大小和形状，连通性的某些方面以及功能组织的细节）可能与活动有关。此外，对于主场与非主场，基因相对于活性的作用及其相互作用可能不同。尽管它们产生的具体表型不是。另一方面，新皮层组织的各个方面（如感觉区域分配，皮层区域的大小和形状，连通性的某些方面以及功能组织的细节）可能与活动有关。此外，对于主场与非主场，基因相对于活性的作用及其相互作用可能不同。