A splicing mutation in the ikbkap gene causes Familial Dysautonomia (FD), affecting the IKAP protein expression levels and proper development and function of the peripheral nervous system (PNS). Here we attempted to elucidate the role of IKAP in PNS development in the chick embryo and found that IKAP is required for proper axonal outgrowth, branching, and peripheral target innervation. Moreover, we demonstrate that IKAP colocalizes with activated JNK (pJNK), dynein, and β-tubulin at the axon terminals of dorsal root ganglia (DRG) neurons, and may be involved in transport of specific target derived signals required for transcription of JNK and NGF responsive genes in the nucleus. These results suggest the novel role of IKAP in neuronal transport and specific signaling mediated transcription, and provide, for the first time, the basis for a molecular mechanism behind the FD phenotype.

Retinoic acid (RA) signalling ensures that vertebrate mesoderm segmentation is bilaterally synchronized, and corrects transient interferences from asymmetric left-right (L-R) signals involved in organ lateralization. Snail genes participate in both these processes and, although they are expressed symmetrically in the presomitic mesoderm (PSM), Snail1 transcripts are asymmetrically distributed in the L-R lateral mesoderm. We show that the alteration of the symmetric Snail expression in the PSM induces asynchronous somite formation. Furthermore, in the absence of RA signalling, normal asymmetric Snail1 expression in the lateral mesoderm is extended to the PSM, desynchronizing somitogenesis. Thus, Snail1 is the first cue corrected by RA in the PSM to ensure synchronized bilateral segmentation.

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In all developing epithelia, the nuclei continually migrate between the apical and basal sides of the cell during the cell cycle, with S phase occurring basally and mitosis occurring apically. The purpose and mechanism of this nuclear migration are unknown. Here, we show that nitric oxide (NO) is endogenously produced in the developing chicken neural tube, where it apparently regulates cell-cycle progression. We provide evidence that high NO levels promote entry into S phase basally, whereas low levels of NO facilitate entry into mitosis apically.