Embryonic expression of the myelin basic protein gene: identification of a promoter region that targets transgene expression to pioneer neurons.
The myelin basic protein (MBP) gene produces two families of structurally related proteins from three different promoters-the golli products, generated from the most upstream promoter, and the MBPs, produced from the two downstream promoters. In this report we describe the expression of golli proteins within some of the earliest neuronal populations of the brain, including Cajal-Retzius cells and preplate neurons of the forebrain, representing a new marker for these cells. To identify elements responsible for neuronal expression of the golli products, we generated transgenic animals from constructs containing different portions of the upstream promoter. A construct containing 1.1 kb immediately upstream of the golli transcription start site targeted expression of beta-galactosidase to preplate neurons and a subset of Cajal-Retzius cells in transgenic mice-the first reported genetic element to target expression to these pioneer cortical populations. Although expression in Cajal-Retzius cells declined with embryonic development, preplate cells continued to express the transgene after arriving at their final destination in the subplate. Interestingly, expression persisted in subplate neurons found within a distinct layer between the white matter and cortical layer VI well into postnatal life. Birth dating studies with bromodeoxyuridine indicated that these neurons were born between E10.5 and E12.5. Thus, the transgene marked subplate neurons from their birth, providing a fate marker for these cells. This work suggests a role for the MBP gene in the early developing brain long before myelination and especially in the pioneer cortical neurons important in the formation of the cortical layers.
Landry
C F
CF
Developmental Biology Group, Neuropsychiatric Institute, University of California at Los Angeles, School of Medicine, Los Angeles, California 90024, USA.
Pribyl
T M
TM
Ellison
J A
JA
Givogri
M I
MI
Kampf
K
K
Campagnoni
C W
CW
Campagnoni
A T
AT
D000367:Age Factors; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012326:RNA Splicing / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D001616:beta-Galactosidase / Q000235:genetics
D004676:Myelin Basic Protein; D012333:RNA, Messenger; D001616:beta-Galactosidase