Murphy M, Reid K, Brown M A, Bartlett P F
Walter and Eliza Hall Institute of Medical Research, Royal Melboune Hospital, Parkville, Victoria, Australia.
Development. 1993 Mar;117(3):1173-82. doi: 10.1242/dev.117.3.1173.
Leukemia inhibitory factor (LIF) was recently shown to stimulate the generation of sensory neurons from the murine neural crest in vitro. Here, we examine the respective activities of LIF and nerve growth factor (NGF) throughout the embryonic development of sensory neurons in dorsal root ganglia (DRG) and neural crest. In cultures of embryonic day 12 (E12) DRG, which contain sensory neuron precursor cells, a combination of both LIF and NGF are required for the differentiation of mature sensory neurons from their neurofilament negative (NF-) precursors. The primary differentiation step from NF- cell to NF+ immature neuron is promoted by LIF, whereas the survival and further maturation of the newly differentiated neurons depends on NGF. In cultures of sensory neurons isolated at the time of target innervation (E14 and E15 DRG), the survival of the majority of the neurons is dependent on NGF. However, LIF acts as a survival agent for a discrete population of NGF non-responsive neurons. From E16, the number of neurons maintained by LIF increases to > 90% by birth. Consistent with the in vitro observations, LIF mRNA could be detected at early developmental stages (E12-E13), within the spinal column and DRG as well as the limbs and, later (after E15), in areas of sensory innervation (skin, limbs, feet and gut). This supports the idea that LIF, as well as NGF, may regulate sensory development in vivo.
白血病抑制因子（LIF）最近被证明可在体外刺激小鼠神经嵴产生感觉神经元。在此，我们研究了LIF和神经生长因子（NGF）在背根神经节（DRG）和神经嵴中感觉神经元整个胚胎发育过程中的各自活性。在含有感觉神经元前体细胞的胚胎第12天（E12）DRG培养物中，成熟感觉神经元从其神经丝阴性（NF-）前体分化需要LIF和NGF两者的组合。从NF-细胞到NF+未成熟神经元的主要分化步骤由LIF促进，而新分化神经元的存活和进一步成熟则依赖于NGF。在目标神经支配时分离的感觉神经元培养物（E14和E15 DRG）中，大多数神经元的存活依赖于NGF。然而，LIF作为一群对NGF无反应的神经元的存活因子。从E16开始，由LIF维持的神经元数量在出生时增加到>90%。与体外观察结果一致，在发育早期阶段（E12 - E13），在脊柱、DRG以及四肢中可检测到LIF mRNA，随后（E15之后），在感觉神经支配区域（皮肤、四肢、足部和肠道）也可检测到。这支持了LIF以及NGF可能在体内调节感觉发育的观点。
