title: Population-specific regulation of Chmp2b by Lbx1 during onset of synaptogenesis in lateral association interneurons.
abstract: Chmp2b is closely related to Vps2, a key component of the yeast protein complex that creates the intralumenal vesicles of multivesicular bodies. Dominant negative mutations in Chmp2b cause autophagosome accumulation and neurodegenerative disease. Loss of Chmp2b causes failure of dendritic spine maturation in cultured neurons. The homeobox gene Lbx1 plays an essential role in specifying postmitotic dorsal interneuron populations during late pattern formation in the neural tube. We have discovered that Chmp2b is one of the most highly regulated cell-autonomous targets of Lbx1 in the embryonic mouse neural tube. Chmp2b was expressed and depended on Lbx1 in only two of the five nascent, Lbx1-expressing, postmitotic, dorsal interneuron populations. It was also expressed in neural tube cell populations that lacked Lbx1 protein. The observed population-specific expression of Chmp2b indicated that only certain population-specific combinations of sequence specific transcription factors allow Chmp2b expression. The cell populations that expressed Chmp2b corresponded, in time and location, to neurons that make the first synapses of the spinal cord. Chmp2b protein was transported into neurites within the motor- and association-neuropils, where the first synapses are known to form between E11.5 and E12.5 in mouse neural tubes. Selective, developmentally-specified gene expression of Chmp2b may therefore be used to endow particular neuronal populations with the ability to mature dendritic spines. Such a mechanism could explain how mammalian embryos reproducibly establish the disynaptic cutaneous reflex only between particular cell populations.
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, United States of America.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Mariko
authors.initials: M
authors.lastname: Nonogaki
authors.forename: Ravi
authors.initials: R
authors.lastname: Madhira
authors.forename: Hsiao-Yen
authors.initials: HY
authors.lastname: Ma
authors.forename: Ola
authors.initials: O
authors.lastname: Hermanson
authors.forename: Chrissa
authors.initials: C
authors.lastname: Kioussi
authors.forename: Michael K
authors.initials: MK
authors.lastname: Gross
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009046:Motor Neurons / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: C525139:CHMP2B protein, mouse; D056827:Endosomal Sorting Complexes Required for Transport; C491868:Lbx1h protein, mouse; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins