Abstract
Sex-determining region Y box 2 (Sox2), expressed in neural tissues, plays an important role as a transcription factor not only in the pluripotency and proliferation of neuronal cells but also in the opposite function of cell differentiation. Nevertheless, how Sox2 is linked to motor neuron development remains unknown. Here, we showed that Sox2 was localized in the motor neurons of spinal cord by in situ hybridization and cell separation, which acted as a positive regulator of motor neuron development. The deficiency of Sox2 in zebrafish larvae resulted in abnormal PMN development, including truncated but excessively branched CaP axons, loss of MiP, and increase of undifferentiated neuron cells. Importantly, transcriptome analysis showed that Sox2-depleted embryos caused many neurogenesis, axonogenesis, axon guidance, and differentiation-related gene expression changes, which further support the vital function of Sox2 in motor neuron development. Taken together, these data indicate that Sox2 plays a crucial role in the motor neuron development by regulating neuron differentiation and morphology of neuron axons.
Highlights
Motor neuron disease (MND) characterized by muscle weakness or spastic paralysis is a neurodegenerative disease caused by progressive paralysis and death of motor stem neurons in the brainstem or spinal cord (Babin et al, 2014)
In order to further analyze the expression level of Sex-determining region Y box 2 (Sox2) in the zebrafish nervous system and whether it was expressed in the motor neurons, we selected the motor neurons from Tg(mnx1:GFP)ml2 whose motor neurons were labeled by GFP for the RNA extraction
The results of RT-PCR showed that both mnx1 and Sox2 were detected in the selected neuron cells (Figure 1D), which indicated that Sox2 might be expressed in zebrafish motor neurons
Summary
Motor neuron disease (MND) characterized by muscle weakness or spastic paralysis is a neurodegenerative disease caused by progressive paralysis and death of motor stem neurons in the brainstem or spinal cord (Babin et al, 2014). Spinal muscular atrophy (SMA), a hereditary MND that occurs in childhood, is characterized by selective loss of spinal motor neurons. The other is amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disease that causes the degeneration of upper and lower motor neurons with the progressive weakness of muscle (Haramati et al, 2010). Elucidating the mechanisms involved in motor neuron development may variegate therapeutic strategies for MND. Zebrafish is an excellent model system for studying human disease, especially neurobiological related diseases, due to its well-characterized embryo development and the labeled neurons (McWhorter et al, 2003). Motor neurons have precise subtype identities that are characterized by different morphological criteria and extend their axons to different target muscles in a highly specific manner (Shirasaki and Pfaff, 2002; Lewis and Eisen, 2003)
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