The cerebrospinal fluid (CSF) contains an extracellular thread conserved in vertebrates, the Reissner fiber, which controls body axis morphogenesis in the zebrafish embryo. Yet, the signaling cascade originating from this fiber to ensure body axis straightening is not understood. Here, we explore the functional link between the Reissner fiber and undifferentiated spinal neurons contacting the CSF (CSF-cNs). First, we show that the Reissner fiber is required in vivo for the expression of urp2, a neuropeptide expressed in CSF-cNs. We show that the Reissner fiber is also required for embryonic calcium transients in these spinal neurons. Finally, we study how local adrenergic activation can substitute for the Reissner fiber-signaling pathway to CSF-cNs and rescue body axis morphogenesis. Our results show that the Reissner fiber acts on CSF-cNs and thereby contributes to establish body axis morphogenesis, and suggest it does so by controlling the availability of a chemical signal in the CSF.