Ezzeddine Z D, Yang X, DeChiara T, Yancopoulos G, Cepko C L
Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Development. 1997 Mar;124(5):1055-67. doi: 10.1242/dev.124.5.1055.
Lineage analyses of vertebrate retinae have led to the suggestions that cell fate decisions are made during or after the terminal cell division and that extrinsic factors can influence fate choices. The evidence for a role of extrinsic factors is strongest for development of rodent rod photoreceptors ('rods'). In an effort to identify molecules that may regulate rod development, a number of known factors were assayed in vitro. Ciliary neurotrophic factor (CNTF) was found to have a range of effects on retinal cells. Addition of CNTF to postnatal rat retinal explants resulted in a dramatic reduction in the number of differentiating rods. Conversly, the number of cells expressing markers of bipolar cell differentiation was increased to a level not normally seen in vivo or in vitro. In addition, a small increase in the percentage of cells expressing either a marker of amacrine cells or a marker of Muller glia was noted. It was determined that many of the cells that would normally differentiate into rods were the cells that differentiated as bipolar cells in the presence of CNTF. Prospective rod photoreceptors could make this change even when they were postmitotic, indicating that at least a subset of cells fated to be rods were not committed to this fate at the time they were born. These findings highlight the distinction between cell fate and commitment. Resistance to the effect of CNTF on rod differentiation occurred at about the time that a cell began to express opsin. The time of commitment to terminal rod differentiation may thus coincide with the initiation of opsin expression. In agreement with the hypothesis that CNTF plays a role in rod differentiation in vivo, a greater percentage of cells were observed differentiating as rod photoreceptors in mouse retinal explants lacking a functional CNTF receptor, relative to wild-type littermates.
脊椎动物视网膜的谱系分析表明，细胞命运决定是在终末细胞分裂期间或之后做出的，并且外在因素可以影响命运选择。外在因素在啮齿动物视杆光感受器（“视杆细胞”）发育中的作用证据最为充分。为了确定可能调节视杆细胞发育的分子，在体外对一些已知因素进行了检测。发现睫状神经营养因子（CNTF）对视网膜细胞有一系列影响。将CNTF添加到出生后大鼠视网膜外植体中，导致分化中的视杆细胞数量显著减少。相反，表达双极细胞分化标志物的细胞数量增加到体内或体外通常未见的水平。此外，观察到表达无长突细胞标志物或穆勒胶质细胞标志物的细胞百分比略有增加。已确定，许多正常情况下会分化为视杆细胞的细胞，在存在CNTF的情况下分化为双极细胞。即使在有丝分裂后，预期的视杆光感受器也能发生这种变化，这表明至少一部分注定成为视杆细胞的细胞在出生时并未确定这种命运。这些发现突出了细胞命运和细胞定型之间的区别。对CNTF对视杆细胞分化作用的抗性大约在细胞开始表达视蛋白时出现。因此，终末视杆细胞分化的定型时间可能与视蛋白表达的起始时间一致。与CNTF在体内视杆细胞分化中起作用的假设一致，相对于野生型同窝小鼠，在缺乏功能性CNTF受体的小鼠视网膜外植体中，观察到有更大比例的细胞分化为视杆光感受器。
