Expression patterns and behavioral effects of conopressin and APGWamide in the nudibranch Berghia stephanieae.

The highly conserved oxytocin/vasopressin family of nonapeptides plays many roles across the animal kingdom, from osmoregulation to reproductive physiology. We investigated the expression patterns and pharmacological effects of the gastropod ortholog of this peptide, conopressin, along with another peptide involved in gastropod reproduction, APGWamide, in the nudibranch Berghia stephanieae. A brain transcriptome was used to identify and annotate the gene sequences for the peptides and one conopressin receptor. In-situ hybridization chain reaction showed that many neurons in the brain expressed these peptides. However, the peptide genes were co-expressed by only three neurons, which were in the right cerebral ganglion, the same side on which the reproductive organs are located. A conopressin receptor (BSCPR1) was expressed in a prominent population of APGWamide expressing neurons. Placing animals in a solution containing the APGWamide peptide caused minimal behavioral changes. However, exposure to conopressin reduced locomotion, increased gut contractions, and caused voiding at high concentration. The genes for these peptides and BSCPR1 were expressed in cells in the digestive system. BSCPR1 was also expressed by a line of neurons on the anterior portion of the radula and would be contacted during feeding. APGWamide-expressing neurons were found in the genital ganglion. All three genes expressed in cells on sensory appendages. These results are consistent with the conopressin playing a variety of roles in the brain and the body and being involved in both reproduction and digestion. This study sheds light on the function of this ancient nonapeptide in a new-to-neuroscience invertebrate species.

Transcriptome analysis in a humanized mouse model of familial dysautonomia reveals tissue-specific gene expression disruption in the peripheral nervous system.

Familial dysautonomia (FD) is a rare recessive neurodevelopmental disease caused by a splice mutation in the Elongator acetyltransferase complex subunit 1 (ELP1) gene. This mutation results in a tissue-specific reduction of ELP1 protein, with the lowest levels in the central and peripheral nervous systems (CNS and PNS, respectively). FD patients exhibit complex neurological phenotypes due to the loss of sensory and autonomic neurons. Disease symptoms include decreased pain and temperature perception, impaired or absent myotatic reflexes, proprioceptive ataxia, and progressive retinal degeneration. While the involvement of the PNS in FD pathogenesis has been clearly recognized, the underlying mechanisms responsible for the preferential neuronal loss remain unknown. In this study, we aimed to elucidate the molecular mechanisms underlying FD by conducting a comprehensive transcriptome analysis of neuronal tissues from the phenotypic mouse model TgFD9; Elp1Δ20/flox. This mouse recapitulates the same tissue-specific ELP1 mis-splicing observed in patients while modeling many of the disease manifestations. Comparison of FD and control transcriptomes from dorsal root ganglion (DRG), trigeminal ganglion (TG), medulla (MED), cortex, and spinal cord (SC) showed significantly more differentially expressed genes (DEGs) in the PNS than the CNS. We then identified genes that were tightly co-expressed and functionally dependent on the level of full-length ELP1 transcript. These genes, defined as ELP1 dose-responsive genes, were combined with the DEGs to generate tissue-specific dysregulated FD signature genes and networks. Within the PNS networks, we observed direct connections between Elp1 and genes involved in tRNA synthesis and genes related to amine metabolism and synaptic signaling. Importantly, transcriptomic dysregulation in PNS tissues exhibited enrichment for neuronal subtype markers associated with peptidergic nociceptors and myelinated sensory neurons, which are known to be affected in FD. In summary, this study has identified critical tissue-specific gene networks underlying the etiology of FD and provides new insights into the molecular basis of the disease.