Homeodomain Interacting Protein Kinase 2 Regulates Postnatal Development of Enteric Dopaminergic Neurons and Glia via BMP Signaling

• DOI: 10.1523/jneurosci.1078-11.2011
• Publication Date: 2011-09-28T20:25:18Z
• Authors: Alcmène Chalazonitis; Amy A. Tang; Yulei Shang; Tuan D. Pham; Ivy Hsieh; Wanda Setlik; Michael D. Gershon; Eric J. Huang
• Keywords: Enteric Nervous System; Gliogenesis

Trophic factor signaling is important for the migration, differentiation, and survival of enteric neurons during development. The mechanisms that regulate maturation in postnatal life, however, are poorly understood. Here, we show transcriptional cofactor HIPK2 (homeodomain interacting protein kinase 2) required regulating gliogenesis Mice lacking display a spectrum gastrointestinal (GI) phenotypes, including distention colon slowed GI transit time. Although loss does not affect prenatal development, progressive occurs life Hipk2 −/− mutant mice preferentially affects dopaminergic population caudal region intestine. mechanism by which regulates neuron development appears to involve response bone morphogenetic proteins (BMPs). Specifically, compared wild type mice, larger proportion mutants have an abnormally high level phosphorylated Smad1/5/8. Consistent with ability BMP promote gliogenesis, significant increase glia nervous system. In addition, numbers autophagosomes increased mutants, synaptic arrested. These results reveal new role as pathway maintenance glia, further suggest its associated may be therapeutically altered neuronal maturation.