title: Detailed expression analysis of regulatory genes in the early developing human neural tube.
abstract: Studies in model organisms constitute the basis of our understanding of the principal molecular mechanisms of cell fate determination in the developing central nervous system. Considering the emergent applications in stem cell-based regenerative medicine, it is important to demonstrate conservation of subtype specific gene expression programs in human as compared to model vertebrates. We have examined the expression patterns of key regulatory genes in neural progenitor cells and their neuronal and glial descendants in the developing human spinal cord, hindbrain, and midbrain, and compared these with developing mouse and chicken embryos. As anticipated, gene expression patterns are highly conserved between these vertebrate species, but there are also features that appear unique to human development. In particular, we find that neither tyrosine hydroxylase nor Nurr1 are specific markers for mesencephalic dopamine neurons, as these genes also are expressed in other neuronal subtypes in the human ventral midbrain and in human embryonic stem cell cultures directed to differentiate towards a ventral mesencephalic identity. Moreover, somatic motor neurons in the ventral spinal cord appear to be produced by two molecularly distinct ventral progenitor populations in the human, raising the possibility that the acquisition of unique ventral progenitor identities may have contributed to the emergence of neural subtypes in higher vertebrates.
authors.affiliation: 1 Department of Cell and Molecular Biology, Karolinska Institutet , Stockholm, Sweden .
authors.forename: Ulrika
authors.initials: U
authors.lastname: Marklund
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Alekseenko
authors.forename: Elisabet
authors.initials: E
authors.lastname: Andersson
authors.forename: Scott
authors.initials: S
authors.lastname: Falci
authors.forename: Magnus
authors.initials: M
authors.lastname: Westgren
authors.forename: Thomas
authors.initials: T
authors.lastname: Perlmann
authors.forename: Anthony
authors.initials: A
authors.lastname: Graham
authors.forename: Erik
authors.initials: E
authors.lastname: Sundström
authors.forename: Johan
authors.initials: J
authors.lastname: Ericson
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology*; D051379:Mice; D009046:Motor Neurons / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology*; D009474:Neurons / Q000166:cytology; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
chemical_list: C539882:NR4A2 protein, human; D009419:Nerve Tissue Proteins; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014446:Tyrosine 3-Monooxygenase