Transgenic songbirds with suppressed or enhanced activity of CREB transcription factor

Abstract

Songbirds postnatally develop their skill to utter and to perceive a vocal signal for communication. How genetic and environmental influences act in concert to regulate the development of such skill is not fully understood. Here, we report the phenotype of transgenic songbirds with altered intrinsic activity of cAMP response element-binding protein (CREB) transcription factor. By viral vectormediated modification of genomic DNA, we established germ linetransmitted lines of zebra finches, which exhibited enhanced or suppressed activity of CREB. Although intrinsically acquired vocalizations or their hearing ability were not affected, the transgenic birds showed reduced vocal learning quality of their own songs and impaired audio-memory formation against conspecific songs. These results thus demonstrate that appropriate activity of CREB is necessary for the postnatal acquisition of learned behavior in songbirds, and the CREB transgenic birds offer a unique opportunity to separately manipulate both genetic and environmental factors that impinge on the postnatal song learning.songbird | CREB | transgenic animal | vocal learning | postnatal development

Insights into the Neural and Genetic Basis of Vocal Communication

“…In addition, knockdown of the transcription factor FoxP2 in songbirds disrupts song development in a manner similar to disruptions seen in human speech development, indicating analogous circuit and gene regulatory mechanisms for song and speech (Fisher and Scharff, 2009; Haesler et al, 2007; Haesler et al, 2004; Lai et al, 2001; Murugan et al, 2013). Despite these important behavioral and neurobiological parallels between birdsong and speech, studies in songbirds have been limited by the lack of methods for efficiently and precisely editing the avian genome; however, the recent development of transgenic songbirds (Abe et al, 2015; Agate et al, 2009; Liu et al, 2015; Scott et al, 2010), advances in viral vector methods and gene editing tools (Betley and Sternson, 2011; Heidenreich and Zhang, 2016; Roberts et al, 2012; Roberts et al, 2010), and the sequencing of the avian genome (Warren et al, 2010; Zhang et al, 2014) all promise to enrich the continued use of songbirds in the study of speech disorders.…”

Transgenesis and Genome Editing in Poultry

“…With precise genome modulation of ovarian cancer-related genes in an avian model, especially chickens, it is possible to reveal the genetic mechanisms of ovarian cancer. In addition, avian genome-editing tools will gradually be applied to other birds, such as zebra finch, which is an exclusive non-human model organism for investigating the biological basis of speech learning and neurobehavioral research and disease [130][131][132][133][134]. Until now, direct injection of virus-mediated transgenesis into embryos has been used in zebra finch [132].…”

Full Issue

“…CREB is a transcription factor and an important component of an intracellular signaling system regulating a wide range of biological functions from spermatogenesis to circadian rhythms and memory (Silva et al 1998). CREB-responsive transcription plays a central role in learning and memory formation as well as retrieval across a variety of taxa ranging from insects (Goda 1995) and mollusks (Silva et al 1998) to birds (Abe et al 2015) and mammals (Yin andTully 1996, Silva et al 1998). Moreover, hippocampal expression of CREB correlates with performance on memory tasks (Alberini 2009).…”