Abstract
BackgroundDorsoventral patterning of the developing spinal cord is important for the correct generation of spinal neuronal types. This process relies in part on cross-repressive interactions between specific transcription factors whose expression is regulated by Sonic hedgehog. Groucho/transducin-like Enhancer of split (TLE) proteins are transcriptional corepressors suggested to be recruited by at least certain Sonic hedgehog-controlled transcription factors to mediate the formation of spatially distinct progenitor domains within the ventral spinal cord. The aim of this study was to characterize the involvement of TLE in mechanisms regulating the establishment of the boundary between the most ventral spinal cord progenitor domains, termed pMN and p3. Because the pMN domain gives rise to somatic motor neurons while the p3 domain generates V3 interneurons, we also examined the involvement of TLE in the acquisition of these neuronal fates.Methodology and Principal FindingsA combination of in vivo loss- and gain-of-function studies in the developing chick spinal cord was performed to characterize the role of TLE in ventral progenitor domain formation. It is shown here that TLE overexpression causes increased numbers of p3 progenitors and promotes the V3 interneuron fate while suppressing the motor neuron fate. Conversely, dominant-inhibition of TLE increases the numbers of pMN progenitors and postmitotic motor neurons.ConclusionBased on these results, we propose that TLE is important to promote the formation of the p3 domain and subsequent generation of V3 interneurons.
Highlights
Patterning of the vertebrate central nervous system (CNS) results in the generation of specific neural cell types in precise regions of the CNS
Based on these results, we propose that transducin-like Enhancer of split (TLE) is important to promote the formation of the p3 domain and subsequent generation of V3 interneurons
This observation suggests that TLE proteins are expressed in the pMN progenitor domain
Summary
Patterning of the vertebrate central nervous system (CNS) results in the generation of specific neural cell types in precise regions of the CNS. The transduction of the Shh concentration gradient into a differential expression of separate Class I and Class II HD and bHLH transcription factors throughout the ventral spinal cord results in the appearance of separate groups of neural progenitor cells expressing different combinations of Shh-regulated proteins. Different Shh-regulated transcription factors become segregated to defined domains in the ventral spinal cord, so that only one transcription factor of a given cross-repressive pair is expressed in a particular progenitor domain [3,4]. Dorsoventral patterning of the developing spinal cord is important for the correct generation of spinal neuronal types This process relies in part on cross-repressive interactions between specific transcription factors whose expression is regulated by Sonic hedgehog. Because the pMN domain gives rise to somatic motor neurons while the p3 domain generates V3 interneurons, we examined the involvement of TLE in the acquisition of these neuronal fates
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