Retinoic acid controls proper head-to-trunk linkage in zebrafish by regulating an anteroposterior somitogenetic rate difference

Abstract

During vertebrate development, the primary body axis elongates towards the posterior and is periodically divided into somites, which give rise to the vertebrae, skeletal muscles and dermis. Somites form periodically from anterior to posterior, and the anterior somites form in a more rapid cycle than the posterior somites. However, how this anteroposterior (AP) difference in somitogenesis is generated and how it contributes to the vertebrate body plan remain unclear. Here, we show that the AP difference in zebrafish somitogenesis originates from a variable overlapping segmentation period between one somite and the next. The AP difference is attributable to spatiotemporal inhibition of the clock gene her1 via retinoic acid (RA) regulation of the transcriptional repressor ripply1. RA depletion thus disrupts timely somite formation at the transition, eventually leading to the loss of one somite and the resultant cervical vertebra. Overall, our results indicate that RA regulation of the AP difference is crucial for proper linkage between the head and trunk in the vertebrate body plan.

Time-lapse observation of stepwise regression of Erk activity in zebrafish presomitic mesoderm

“…As a control, Erk biosensor mRNA (100 pg) or Erk biosensor mRNA (100 pg) and control -MO (12.5 ng) were injected. Injected embryos were developed until the 7SS stage, dechorionated, and mounted laterally in 1% low melting point agarose at the indicated stages as described previously 29 .…”

New Insights Into the Roles of Retinoic Acid Signaling in Nervous System Development and the Establishment of Neurotransmitter Systems

“…The neural plate, for instance, is initially anterior-like and increasing levels of RA signaling are required in order to specify the more posterior domains of the hindbrain and spinal chord (Blumberg et al, 1997;Cai et al, 2012;Dupé and Lumsden, 2001;Grandel et al, 2002;Lara-Ramírez et al, 2013). Similarly, graded RA signals provide inductive positional cues in the foregut endoderm and trunk mesoderm that contribute to the correct specification and development of their derivatives, including the posterior pharyngeal arches (Kopinke et al, 2006), lung (Chen et al, 2010), pancreas (Huang et al, 2014;Zhang et al, 2013), somites Moreno and Kintner, 2004;Retnoaji et al, 2014), kidney (Le Bouffant et al, 2012;Takayama et al, 2014), heart (Zaffran et al, 2014;Zaffran and Niederreither, 2015) and limbs Monaghan and Maden, 2012). RA signaling has also been implicated in skeletogenesis and liver morphogenesis, but its precise roles are still poorly understood (Green et al, 2016;Huang et al, 2009;Ijpenberg et al, 2007;Spoorendonk et al, 2008).…”

Characterization of paralogous uncx transcription factor encoding genes in zebrafish

“…In vertebrates, Uncx is transcribed in sclerotomal cells surrounding the notochord, suggesting a conserved role as determinant of axial skeleton morphogenesis (Neidhardt et al, 1997; Mansouri et al, 1997; Koudijs et al, 2008; Sánchez and Sánchez, 2013; Retnoaji et al, 2014). Uncx functions are perhaps best understood in amniotes.…”