Developmental neuroscienceAbsence of Reelin results in altered nociception and aberrant neuronal positioning in the dorsal spinal cord
Section snippets
Animal and tissue preparation
The reeler mice (B6C3Fe -a/a- Reln/rl, Jackson Laboratory, Bar Harbor, ME, USA) were obtained from a breeding colony maintained at UCLA. Mice were studied at embryonic (E12.5–17.5), postnatal (P14-19) and adult (3–6 mo) ages. The adult reeler mutants used for sensory tests were healthy, but displayed ataxia, inability to rear on their hind limbs and were smaller than the wild-type controls. Mice were genotyped using polymerase chain reaction screening as adapted from D’Arcangelo et al. (1996).
Pattern of Reelin expression in the superficial dorsal horn
We used immunocytochemistry in coronal sections from wild-type mice to map and analyze the expression pattern of Reelin and detected Reelin-immunoreactive cells in E12.5 dorsal horn (arrows, Fig. 1A). Labeled neurons were scattered near the base of the dorsal horn, with a few cells located near the dorsal root entry zone. On E13.5, Reelin-labeled cells (arrows, Fig. 1C) were concentrated along the ventrolateral border of the dorsal horn, and by E14.5 they occupied the mediolateral extent of
Discussion
In the present study we used immunocytochemistry to characterize Reelin and Dab1 expression in the developing dorsal horn so as to identify positional errors in regions that process nociceptive information. During embryonic development Reelin and Dab1 are expressed in nearby neurons within the superficial dorsal horn, lateral lamina V, and in the LSN, areas associated with the processing of nociceptive information. In addition to identifying notable positional errors and moderate alterations in
Acknowledgments
This work was supported by the National Science Foundation (IBN-9734550, IOB-0518714, P.E.P.), MARC U*Star Fellowship (S.A.V.), and NICHD MRDD Training Fellowship (A.L.A.). We thank Drs. T. Curran, J. Herz, D. Julius, and S. Magdaleno for their generous antibody gifts. We also thank S. Shields for her assistance with sensory testing, Dr. A. Garfinkel for his statistical advice, and Dr. E. Carpenter for her comments on the manuscript.
References (51)
- et al.
The cells of origin of the spinothalamic tract of the rata quantitative reexamination
Brain Res
(1990) - et al.
Quantitative assessment of tactile allodynia in the rat paw
J Neurosci Methods
(1994) - et al.
Reelin is a ligand for lipoprotein receptors
Neuron
(1999) - et al.
Detection of the reelin breakpoint in reeler mice
Mol Brain Res
(1996) - et al.
A panel of monoclonal antibodies against reelin, the extracellular matrix protein defective in reeler mutant mice
J Neurosci Methods
(1998) - et al.
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Pain
(1988) - et al.
Direct binding of Reelin to VLDL receptor and ApoE receptor 2 induces tyrosine phosphorylation of disabled-1 and modulates tau phosphorylation
Neuron
(1999) - et al.
The types of neuron in spinal dorsal horn which possess neurokinin-1 receptors
Neuroscience
(1995) - et al.
Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway
Neuron
(2004) - et al.
Axon terminals possessing α2c-adrenergic receptors densely innervate neurons in the rat lateral spinal nucleus which respond to noxious stimulation
Neuroscience
(2004)
Evidence for a cell-specific action of Reelin in the spinal cord
Dev Biol
A population of large lamina I projection neurons with selective inhibitory input in rat spinal cord
Neuroscience
The Reelin pathway modulates the structure and function of retinal synaptic circuitry
Neuron
Terminal axonal patterns in cat spinal cord. II. The dorsal horn
Brain Res
Tackling pain at the sourceNew ideas about nociceptors
Neuron
The cloned capsaicin receptor integrates multiple pain-producing stimuli
Neuron
Reeler/disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2
Cell
Reelin and ApoE receptors cooperate to enhance hippocampal synaptic plasticity and learning
J Biol Chem
Ectopic sympathetic preganglionic neurons maintain proper connectivity in the reeler mutant mouse
Neuroscience
The development of the rat spinal cord
Adv Anat Embryol Cell Biol
Regulation of protein tyrosine kinase signaling by substrate degradation during brain development
Mol Cell Biol
Distinct neurochemical features of acute and persistent pain
Proc Natl Acad Sci U S A
Cortical neuronal migration mutants suggest separate but intersecting pathways
Annu Rev Cell Dev Biol
Reelin regulates the development and synaptogenesis of the layer-specific entorhino-hippocampal connections
J Neurosci
Morphological characterization of substance P receptor-immunoreactive neurons in the rat spinal cord and trigeminal nucleus caudalis
J Comp Neurol
Cited by (40)
The specification and generation of neurons in the ventral spinal cord
2020, Patterning and Cell Type Specification in the Developing CNS and PNS: Comprehensive Developmental Neuroscience, Second EditionNew perspectives on the mechanisms establishing the dorsal-ventral axis of the spinal cord
2019, Current Topics in Developmental BiologyCitation Excerpt :Seven laminae contain neurons with distinct physiological properties; some neurons locally process afferent sensory information while others relay it to higher order centers in the brain including the brainstem, thalamus and cerebellum (Bermingham et al., 2001; Brown & Fyffe, 1981; Lai et al., 2016; Yasaka, Tiong, Hughes, Riddell, & Todd, 2010). Information about nociception (pain) (Villeda, Akopians, Babayan, Basbaum, & Phelps, 2006; Xu et al., 2013; Yasaka et al., 2010) or thermosensation (temperature) is processed in layers I-II, the most superficial layers of the horn (Bautista et al., 2007; Szabo et al., 2015). Somatosensation (touch) is processed in the intermediate layers, III-IV (Bourane, Grossmann, et al., 2015), and finally, proprioception, or perception of where your body resides in space, is processed in the deep horn, layers V-VI (Miesegaes et al., 2009; Yang, Bermingham, Finegold, & Zoghbi, 2001; Yuengert et al., 2015) (Fig. 1B).
Common cues wire the spinal cord: Axon guidance molecules in spinal neuron migration
2019, Seminars in Cell and Developmental BiologyCitation Excerpt :For example, the Reelin gene, which plays a key role in the radial migration of cortical neurons [31,32], is expressed in the VZ in E9.5 mice [33]. The reeler mice, which express a mutant Reelin, display various defects in spinal neuron migration [34–36]. Although spinal neuroprogenitors are reported to be able to exit the VZ in reeler mice [34], It is not known if the timing is affected.
The Specification and Generation of Neurons in the Ventral Spinal Cord
2013, Comprehensive Developmental Neuroscience: Patterning and Cell Type Specification in the Developing CNS and PNS
- 1
S.A.V. and A.L.A. contributed equally to this work.