Effect of sonic hedgehog on motor neuron positioning in the spinal cord during chicken embryonic development

Abstract

Sonic hedgehog (SHH) is a vertebrate homologue of the secreted Drosophila protein hedgehog and is expressed by the notochord and floor plate in the developing spinal cord. Sonic hedgehog provides signals relevant for positional information, cell proliferation and possibly cell survival, depending on the time and location of expression. Although the role of SHH in providing positional information in the neural tube has been experimentally proven, the underlying mechanism remains unclear. In this study, in ovo electroporation was employed in the chicken spinal cord during chicken embryo development. Electroporation was conducted at stage 17 (E2.5), after electroporation the embryos were continued incubating to stage 28 (E6) for sampling, tissue fixation with 4% paraformaldehyde and frozen sectioning. Sonic hedgehog and related protein expressions were detected by in situ hybridization and fluorescence immunohistochemistry and the results were analysed after microphotography. Our results indicate that the ectopic expression of SHH leads to ventralization in the spinal cord during chicken embryonic development by inducing abnormalities in the structure of the motor column and motor neuron integration. In addition, ectopic SHH expression inhibits the expression of dorsal transcription factors and commissural axon projections. The correct location of SHH expression is vital to the formation of the motor column. Ectopic expression of SHH in the spinal cord not only affects the positioning of motor neurons, but also induces abnormalities in the structure of the motor column. It leads to ventralization in the spinal cord, resulting in the formation of more ventral neurons forming during neuronal formation.

The role of Shh signalling pathway in central nervous system development and related diseases

“…Shh deficiency affects not only the formation of spinal cord structures, but also brain development 5 . In our previous studies, in vivo electroporation was employed to achieve the ectopic expression of Shh in the developing chicken spinal cord 46 . Compared with the control group, the abnormal morphology and structure of the spinal cord were observed in Shh ectopic expression group.…”

“…In past study have showed that Shh ectopic expression in dorsal of spinal cord could inhibited the expression of Pax family. In ventral of spinal cord, Shh overexpression could affect the motor neuron positioning of MNR2 positive motor neurons 46 . In fact, Shh regulates the expression of numerous proteins in the spinal cord.…”

Ectopic Posterior Pituitary, Polydactyly, Midfacial Hypoplasia and Multiple Pituitary Hormone Deficiency due to a Novel Heterozygous IVS11-2A>C(c.1957-2A>C) Mutation in the <i>GLI2</i> Gene

“…The sonic hedgehog (SHH) signalling pathway regulates differentiation, proliferation, tissue polarity, stem cell population, and carcinogenesis of the notochord and floor plate in the developing spinal cord ( 1 , 2 ). The SHH signalling pathway is mediated by three related zinc-finger transcription factors (GLI1, GLI2, and GLI3) which are members of the GLI-Kruppel family.…”

Time Course Transcriptome Analysis of Spina Bifida Progression in Fetal Rats

“…Similarly, KEGG pathway analysis also predicted hedgehog signaling to be upregulated, which was previously implicated in neural tube defects [ 4 ]. Abnormal hedgehog signaling decreases the survival of neuronal precursors and alters the position of motor neurons resulting in abnormalities in the structure of the motor column [ 20 , 21 ]. Motor neuron function may also potentially be impacted through hedgehog signaling effects on cellular retinoic acid-binding protein 1 (CRABP1) in which variants were observed in patients with neural tube defects [ 22 , 23 ].…”