Abstract
Phox2a is a vertebrate homeodomain protein expressed in subsets of differentiating neurons. Here, we show that it is essential for proper development of the locus coeruleus, a subset of sympathetic and parasympathetic ganglia and the VIIth, IXth, and Xth cranial sensory ganglia. In the sensory ganglia, we have identified two differentiation blocks in Phox2a-/- mice. First, the transient expression of dopamine-beta-hydroxylase in neuroblasts is abolished, providing evidence that Phox2a controls noradrenergic traits in vivo. Second, the expression of the GDNF receptor subunit Ret is dramatically reduced, and there is a massive increase in apoptosis of ganglion cells, which are known to depend on GDNF in vivo. Therefore, Phox2a appears to regulate conventional differentiation traits and the ability of neurons to respond to essential survival factors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Cell Differentiation
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Cranial Nerves / abnormalities
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Cranial Nerves / embryology
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Dopamine beta-Hydroxylase / biosynthesis
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Drosophila Proteins*
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Embryonic and Fetal Development / genetics
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Enzyme Induction
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Female
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Ganglia, Autonomic / abnormalities*
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Ganglia, Autonomic / embryology
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Ganglia, Sensory / abnormalities*
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Ganglia, Sensory / embryology
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology*
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Locus Coeruleus / abnormalities*
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Locus Coeruleus / embryology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Morphogenesis / genetics
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Nerve Growth Factors*
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Nerve Tissue Proteins / biosynthesis
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Norepinephrine / physiology
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases / biosynthesis
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Recombinant Fusion Proteins / metabolism
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transgenes
Substances
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Drosophila Proteins
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Gdnf protein, mouse
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Homeodomain Proteins
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Nerve Growth Factors
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Nerve Tissue Proteins
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Phox2a protein, mouse
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Transcription Factors
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Dopamine beta-Hydroxylase
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Ret protein, Drosophila
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Ret protein, mouse
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Norepinephrine