Cheng Chi Wa, Yan Carol Hiu Mei, Choy Siu Wah, Hui Michelle Nga Yu, Hui Chi-Chung, Cheng Shuk Han
Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong.
Dev Dyn. 2007 Sep;236(9):2661-7. doi: 10.1002/dvdy.21272.
Serotonergic (5HT) neurons produce neurotransmitter serotonin, which modulates various neuronal circuits. The specification and differentiation of 5HT neurons require both extrinsic signals such as Shh and Fgf, as well as intrinsic transcription factors such as nkx2.2, mash1, phox2b, Gata2, and pet1. In this study, we show that iroquois homeodomain factor irx1a, but not irx1b, is expressed in the 5HT neurons. Knockdown of irx1a by antisense morpholino nucleotides reveals that it is a critical determinant for the differentiation of 5HT neurons in the hindbrain. However, irx1a morphants do not show a reduction of the progenitors of 5HT neurons. Hence, irx1a is not required for the initial specification but it is required for the complete differentiation of 5HT neurons.
血清素能(5HT)神经元产生神经递质血清素,它调节各种神经回路。5HT神经元的特化和分化既需要外在信号,如音猬因子(Shh)和成纤维细胞生长因子(Fgf),也需要内在转录因子,如nkx2.2、mash1、phox2b、Gata2和pet1。在本研究中,我们发现Iroquois同源域因子irx1a而非irx1b在5HT神经元中表达。通过反义吗啉代核苷酸敲低irx1a表明,它是后脑5HT神经元分化的关键决定因素。然而,irx1a morphants并未显示5HT神经元祖细胞数量减少。因此,irx1a对于5HT神经元的初始特化并非必需,但对于其完全分化是必需的。