RESUMEN
In animal retina, hedgehog expression drives waves of neurogenesis, but genetic programs that control its expression during retinal neurogenesis are poorly elucidated. We have previously reported that irx1a is required for propagation of the sonic hedgehog (shh) expression waves in developing zebrafish retina. Here, we found that irx2a is expressed in the developing retina and that knockdown of irx2a results in a retinal phenotype strikingly similar to that of irx1a morphants. The expression of irx2a in retina ganglion cells was shown to be irx1a- and ath5-dependent suggesting that irx1a and ath5 are transcriptional regulators of irx2a. Furthermore, irx2a expression could rescue impaired propagation of shh waves in irx1a morphants. Together, these observations suggest that Irx2 functions downstream of irx1a to control shh expression in the retina. We proposed a novel transcriptional cascade of ath5-irx1a-irx2a in the regulation of hedgehog waves during vertebrate retinal development.
Asunto(s)
Proteínas de Homeodominio/metabolismo , Retina/embriología , Células Ganglionares de la Retina/citología , Factores de Transcripción/metabolismo , Proteínas de Pez Cebra/metabolismo , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Proteínas de Homeodominio/genética , Factores de Transcripción/genética , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
The original hedgehog (hh) gene was found in Drosophila and named for the appearance of a mutant phenotype which causes an embryo to be covered with pointy denticles, thus resembling a hedgehog. The hedgehog family consists of sonic hedgehog (Shh), desert hedgehog (Dhh), and Indian hedgehog (Ihh). Shh is found in vertebrates and the best studied ligand of the hedgehog signaling pathway (Gilbert, 2000). It plays an important role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain, and earlier studies also show that it is important during retinal development (for a review, see Amato et al., 2004). Hedgehog expression drives waves of neurogenesis in animal retina, although genetic programs that control its expression are poorly elucidated. Recently, a novel transcriptional cascade which involves the atonal and Iroquois gene family was proposed in the regulation of hedgehog waves during vertebrate retinal development (Choy et al., 2010). This chapter will focus on Shh by addressing its signaling mechanisms and roles in vertebrate eye development, as well as a novel finding in retinogenesis.
Asunto(s)
Proteínas Hedgehog/metabolismo , Proteínas de Homeodominio/genética , Neurogénesis/genética , Retina/embriología , Transducción de Señal , Animales , Comunicación Celular , Drosophila/genética , Drosophila/metabolismo , Expresión Génica , Proteínas Hedgehog/genética , Humanos , Transducción de Señal/genética , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
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.