primary cilia spinal cord

In the embryonic neural tube, multiple signaling pathways work in concert to create functional neuronal circuits in the adult spinal cord. In the ventral neural tube, Sonic hedgehog (Shh) acts as a graded morphogen to specify neurons necessary for movement. In the dorsal neural tube, bone morphogenetic protein (BMP) and Wnt signals cooperate to specify neurons involved in sensation. Several signaling pathways, including Shh, rely on primary cilia in vertebrates. In this study, we used a mouse mutant with abnormal cilia, Arl13b(hnn), to study the relationship between cilia, cell signaling, and neural tube patterning...

Evolutionarily conserved hedgehog proteins orchestrate the patterning of embryonic tissues, and dysfunctions in their signaling can lead to tumorigenesis. In vertebrates, Sonic hedgehog (Shh) is essential for nervous system development, but the mechanisms underlying its action remain unclear. Early electrical activity is another developmental cue important for proliferation, migration, and differentiation of neurons. Here we demonstrate the interplay between Shh signaling and Ca(2+) dynamics in the developing spinal cord...

Cilia are essential for normal organ function and developmental patterning, but their role in injury and regeneration responses is unknown. To probe the role of cilia in injury, we analyzed the function of foxj1, a transcriptional regulator of cilia genes, in response to tissue damage and renal cyst formation. Zebrafish foxj1a, but not foxj1b, was rapidly induced in response to epithelial distension and stretch, kidney cyst formation, acute kidney injury by gentamicin, and crush injury in spinal cord cells...

On the surface, the Hedgehog (Hh) pathway and primary cilia make strange bedfellows. Hh is a dynamic regulator of a myriad of developmental processes, ranging from spinal cord and limb patterning to lung branching morphogenesis. By contrast, immotile primary cilia were long considered ancestral holdovers with no known function. Considering the disparate perceptions of these two phenomena, the relatively recent discovery that there is a symbiotic-like relationship between Hh and cilia was unexpected. This primer covers the basics of primary cilia and Hh signaling, highlighting variations in ways they are connected across species, and also discusses the evolutionary implications of these findings...

Regulatory factor X (Rfx) homologs regulate the transcription of genes necessary for ciliogenesis in invertebrates and vertebrates. Primary cilia are necessary for Hedgehog signaling and regulation of the activity of the transcriptional regulators known as Gli proteins, which are targets of Hedgehog signaling. Here, we describe an Rfx4(L298P) mouse mutant with distinct dorsoventral patterning defects in the ventral spinal cord and telencephalon due to aberrant Sonic hedgehog (Shh) signaling and Gli3 activity...

Tubby-like protein 3 (TULP3) is required for proper embryonic development in mice. Disruption of mouse Tulp3 results in morphological defects in the embryonic craniofacial regions, the spinal neural tube and the limbs. Here, we show that TULP3 functions as a novel negative regulator of Sonic hedgehog (Shh) signaling in the mouse. In Tulp3 mutants, ventral cell types in the lumbar neural tube, which acquire their identities in response to Shh signaling, are ectopically specified at the expense of dorsal cell types...

Characterization of previously described intraflagellar transport (IFT) mouse mutants has led to the proposition that normal primary cilia are required for mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal primary cilia and shows overactivation of the SHH pathway. The aln locus encodes a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1), which localizes to cilia. aln-mutant cilia have bulb-like structures at their tips in which IFT proteins (such as IFT88) are sequestered, characteristic of Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants...

This article provides a critical analysis of the concepts of the sensory innervation of the brain and spinal cord presented in Sotnikov's articles in issues 2 and 3 of this volume. Criteria for the identification of intracerebral primary sensory neurons and the possible roles of neuronal cilia are discussed. The significance of asynaptic dendrites and bipolar cells is considered. The importance of the correct use of a variety of terms is emphasized, and the need for using combined morphological and electrophysiological analysis in investigating sensory intracerebral exteroceptors is noted...

Published data and our own studies on the sensory innervation of the brain are summarized. Primary interoceptive sensory neurons were analyzed: brain neurons bearing cilia; supraependymal plexuses and intraependymal neurons in contact with the cerebrospinal fluid; Cajal-Retzius neurons in the boundary layer of the cerebral cortex; Dolgo-Saburov paravasal neurons in the brain and spinal cord; Lugaro cells in the cerebellum; and various synaptically NO-positive neurons in the cerebral cortex, whose asynaptic dendrites innervate the precapillary space...

This paper contains a critical analysis of conceptions of the sensory innervation of the spinal cord and the brain, presented in the articles by O.S. Sotnikov (issues 2 and 3 of this journal). The criteria for identification of intracerebral primary sensory neurons are examined, as well as the possible role of neuronal cilia. The significance of asynaptic dendrites and bipolar cells is discussed. The importance of an adequate usage of some terms and the advisability of a combined morphological and physiological analysis for the study of sensory intracerebral exteroceptors is emphasized...

Sonic Hedgehog (Shh) signals are transduced into nuclear ratios of Gli transcriptional activator versus repressor. The initial part of this process is accomplished by Shh acting through Patched (Ptc) to regulate Smoothened (Smo) activity. The mechanisms by which Ptc regulates Smo, and Smo activity is transduced to processing of Gli proteins remain unclear. Recently, a forward genetic approach in mice identified a role for intraflagellar transport (IFT) genes in Shh signal transduction, downstream of Patched (Ptc) and Rab23...

Spinal cord neurons were investigated in embryos of Triturus vulgaris, the smooth newt, just prior to hatching. These embryos can swim if freed from their egg membranes. Horseradish peroxidase (HRP) labelling, together with GABA and glycine immunocytochemistry (ICC), revealed nine distinct anatomical classes of neuron. 1. Ventrolateral motoneurons with mainly dorsal dendrites, sometimes a descending central axon and peripheral axon innervating the trunk muscles. 2. Dorsal primary sensory Rohon-Beard neurons innervating skin and with dorsal ascending and descending axons in spinal cord...