Nkx6 proteins specify one zebrafish primary motoneuron subtype by regulating late islet1 expression

Area of Science:

• Neuroscience
• Developmental Biology
• Molecular Biology

Background:

• Precise connections between motoneurons and muscles are essential for animal behavior.
• Molecular mechanisms governing motoneuron subtype specification are not fully understood.

Purpose of the Study:

• To investigate the role of Nkx6 and Islet1 proteins in vertebrate motoneuron subtype specification.
• To elucidate the molecular pathways regulating the development of specific motoneuron subtypes.

Main Methods:

• Utilized individually identified zebrafish primary motoneurons.
• Analyzed the effects of Nkx6 protein absence and misexpression on motoneuron morphology and gene expression.
• Investigated the regulatory relationship between Nkx6 and Islet1.

Main Results:

• Zebrafish primary motoneurons express two Nkx6 transcription factors.
• Absence of Nkx6 proteins resulted in normal CaP motoneuron development but altered MiP motoneuron morphology towards an interneuron-like fate.
• Nkx6 is required for maintaining Islet1 expression in MiP motoneurons, and Islet1 misexpression can rescue Nkx6 loss-of-function phenotypes.

Conclusions:

• Nkx6 proteins play a novel role in specifying vertebrate motoneuron subtypes.
• Nkx6 regulates MiP development, at least partly, by maintaining Islet1 expression.
• Islet1 acts downstream of Nkx6 to promote MiP subtype identity and suppress interneuron development.