State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China,
Sci China Life Sci. 2013 Nov;56(11):985-93. doi: 10.1007/s11427-013-4543-8. Epub 2013 Sep 5.
Vertebrate development culminates in the generation of proper proportions of a large variety of different cell types and subtypes essential for tissue, organ and system functions in the right place at the right time. Foxn4, a member of the forkhead box/winged-helix transcription factor superfamily, is expressed in mitotic progenitors and/or postmitotic precursors in both neural (e.g., retina and spinal cord) and non-neural tissues (e.g., atrioventricular canal and proximal airway). During development of the central nervous system, Foxn4 is required to specify the amacrine and horizontal cell fates from multipotent retinal progenitors while suppressing the alternative photoreceptor cell fates through activating Dll4-Notch signaling. Moreover, it activates Dll4-Notch signaling to drive commitment of p2 progenitors to the V2b and V2c interneuron fates during spinal cord neurogenesis. In development of non-neural tissues, Foxn4 plays an essential role in the specification of the atrioventricular canal and is indirectly required for patterning the distal airway during lung development. In this review, we highlight current understanding of the structure, expression and developmental functions of Foxn4 with an emphasis on its cell-autonomous and non-cell-autonomous roles in different tissues and animal model systems.
脊椎动物的发育最终产生了大量不同细胞类型和亚型的适当比例，这些细胞类型和亚型对于组织、器官和系统在适当的时间和适当的位置发挥功能至关重要。Foxn4 是叉头框/翼状螺旋转录因子超家族的成员，在神经组织（如视网膜和脊髓）和非神经组织（如房室管和近端气道）的有丝分裂祖细胞和/或有丝分裂后前体细胞中表达。在中枢神经系统的发育过程中，Foxn4 通过激活 Dll4-Notch 信号通路，从多能视网膜祖细胞中特化出无长突细胞和水平细胞命运，同时抑制替代感光细胞命运。此外，它通过激活 Dll4-Notch 信号通路，驱动脊髓神经发生过程中 p2 祖细胞向 V2b 和 V2c 中间神经元命运的决定。在非神经组织的发育过程中，Foxn4 在房室管的特化中起着至关重要的作用，并在肺发育过程中间接参与远端气道的模式形成。在这篇综述中，我们强调了 Foxn4 的结构、表达和发育功能的当前理解，重点介绍了其在不同组织和动物模型系统中的细胞自主和非细胞自主作用。
