The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic . Sensory/Inter/Motor Neuron-Type

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The correct generation and maintenance of the nervous system is critical for the animal’s life. Dysregulation of these processes leads to multiple neurodevelopmental disorders. It has been a daunting challenge not only to identify the developmental mechanisms that determine neuronal cell fate, but also to understand the extent to which the mechanisms are evolutionarily conserved. Here, we describe a developmental mechanism that determines the fate of a specific cholinergic and peptidergic neuronal type in C. elegans. We show that the lim-4 LIM homeodomain transcription factor is necessary and sufficient to promote and maintain the specific cholinergic and peptidergic properties and functions via binding to unique DNA sequences. We also demonstrate that C. elegans lim-4 and human LHX6 show striking functional similarity; specifically, C. elegans LIM-4 or human LHX6 can induce cholinergic and peptidergic characteristics in human neuronal cell lines. Given the high conservation of these transcription factors, these developmental mechanisms are likely to be generally applicable in the nervous system of other organisms as well.

Vyšlo v časopise: The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies the Terminal Identity of a Cholinergic and Peptidergic . Sensory/Inter/Motor Neuron-Type. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005480
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005480

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