ABSTRACT
In the caudal neural tube, oligodendrocyte progenitors (OLPs) originate in the ventral neuroepithelium under the influence of Sonic hedgehog (SHH), then migrate throughout the spinal cord and brainstem before differentiating into myelin-forming cells. We present evidence that oligodendrogenesis in the anterior neural tube follows a similar pattern. We show that OLPs in the embryonic mouse forebrain express platelet-derived growth factor alpha-receptors (PDGFRA), as they do in more caudal regions. They first appear within a region of anterior hypothalamic neuroepithelium that co-expresses mRNA encoding SHH, its receptor PTC1 (PTCH) and the transcription factors OLIG1, OLIG2 and SOX10. Pdgfra-positive progenitors later spread through the forebrain into areas where Shh is not expressed, including the cerebral cortex. Cyclopamine inhibited OLP development in cultures of mouse basal forebrain, suggesting that hedgehog (HH) signalling is obligatory for oligodendrogenesis in the ventral telencephalon. Moreover, Pdgfra-positive progenitors did not appear on schedule in the ventral forebrains of Nkx2.1 null mice, which lack the telencephalic domain of Shh expression. However, OLPs did develop in cultures of Nkx2.1(-/-) basal forebrain and this was blocked by cyclopamine. OLPs also developed in neocortical cultures, even though Shh transcripts could not be detected in the embryonic cortex. Here, too, the appearance of OLPs was suppressed by cyclopamine. In keeping with these findings, we detected mRNA encoding SHH and Indian hedgehog (IHH) in both Nkx2.1(-/-) basal forebrain cultures and neocortical cultures. Overall, the data are consistent with the idea that OLPs in the telencephalon, possibly even some of those in the cortex, develop under the influence of SHH in the ventral forebrain.
Subject(s)
Oligodendroglia/cytology , Proteins/metabolism , Stem Cells/cytology , Telencephalon/cytology , Trans-Activators , Animals , Basic Helix-Loop-Helix Transcription Factors , Cell Differentiation , Cell Lineage , Cells, Cultured , Cerebral Cortex/metabolism , Cerebral Cortex/pathology , DNA-Binding Proteins/genetics , Gene Expression , Genes, Overlapping , Hedgehog Proteins , High Mobility Group Proteins/genetics , Intracellular Signaling Peptides and Proteins , Membrane Proteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Nerve Tissue Proteins/genetics , Oligodendrocyte Transcription Factor 2 , Patched Receptors , Patched-1 Receptor , Prosencephalon/metabolism , Prosencephalon/pathology , Proteins/genetics , Rats , Rats, Sprague-Dawley , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptors, Cell Surface , SOXE Transcription Factors , Telencephalon/metabolism , Transcription FactorsABSTRACT
There are clear parallels between oligodendrocyte development in the spinal cord and forebrain. However, there is new evidence that in both of these regions oligodendrocyte lineage development may be more complex than we earlier thought. This stems from the recent identification of three new transcription factor genes, Olig1, Olig2 and Sox10, that are expressed from the early stages of oligodendrocyte lineage development. In this article, we highlight the common themes underlying specification and early development of oligodendrocytes in the spinal cord and telencephalon. Then, we discuss recent studies of Sox10 and the Olig genes and their implications for oligodendrocyte specification. We conclude that although the mechanisms of oligodendrogenesis appear to be fundamentally similar at different rostro-caudal levels of the neuraxis, there are still many unanswered questions about the details of oligodendrocyte specification.
Subject(s)
Oligodendroglia/cytology , Spinal Cord/cytology , Telencephalon/cytology , Trans-Activators , Animals , Basic Helix-Loop-Helix Transcription Factors , Biomarkers , DNA-Binding Proteins/genetics , DNA-Binding Proteins/physiology , Fetal Proteins/genetics , Fetal Proteins/physiology , Hedgehog Proteins , High Mobility Group Proteins/genetics , High Mobility Group Proteins/physiology , Humans , Mice , Morphogenesis , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/physiology , Oligodendrocyte Transcription Factor 2 , Proteins/genetics , Proteins/physiology , Receptor, Platelet-Derived Growth Factor alpha/analysis , SOXE Transcription Factors , Spinal Cord/embryology , Telencephalon/embryology , Transcription Factors , Transcription, GeneticABSTRACT
Kid1 encodes a transcriptional repressor implicated in the differentiation of renal epithelial cells. Here we report the characterisation of Kid3, a novel mouse gene related to Kid1. Kid3 encodes a C2H2 zinc finger protein with an N-terminal KRAB transcriptional repression domain. It maps to chromosome 11, adjacent to Kid1 and another related gene Kid2. Northern analysis shows that Kid3 is highly expressed in embryonic and adult brain, with lower levels in adult and embryonic (E16.5) kidney, gut, lung and heart. Expression of Kid3 in the kidney is developmentally regulated and suggests a role for Kid3 in the early stages of nephrogenesis.
Subject(s)
DNA-Binding Proteins , Repressor Proteins/genetics , Amino Acid Sequence , Animals , Brain/embryology , Brain/metabolism , Chromosome Mapping , Gene Expression , Gene Library , Kidney/embryology , Kidney/metabolism , Mice , Molecular Sequence Data , Repressor Proteins/chemistry , Sequence Alignment , Zinc Fingers/geneticsABSTRACT
Kid1 encodes a zinc finger protein that has been implicated in renal cell differentiation. Levels of Kid1 mRNA correlate with maturation of kidney tubule epithelia in rat post-natal kidney development and during kidney regeneration following injury. KID1 is a putative transcriptional repressor, containing a KRAB domain at its amino terminus that mediates transcriptional repression in transient cell transfection assays when fused to a heterologous DNA-binding domain. In this paper, we describe the isolation and characterization of the mouse homologue of Kid1 and the identification of a novel highly related mouse gene, Kid2, Kid1 and Kid2 are tightly linked on mouse chromosome 11 and show conservation across mammals. Both genes are expressed predominantly in the mouse adult kidney and brain, but transcripts are also detected in embryonic brain, kidney, gut and lung, suggesting an additional role for these genes during mouse development.