CNTF/LIF/gp130 receptor complex signaling maintains a VZ precursor differentiation gradient in the developing ventral forebrain.
The extrinsic signaling pathways responsible for the formation and maintenance of the unique laminar organization of the forebrain germinal zones are largely unknown. In the present study, we asked whether ciliary neurotrophic factor (CNTF)/leukemia inhibitory factor (LIF)/gp130 signaling plays a role in the development of the germinal layers in the lateral ganglionic eminence. We found that CNTF/LIF/gp130 receptor signaling promotes the self-renewal/expansion of a subpopulation of fibroblast growth factor-responsive ventricular zone (VZ) precursors in the ventral forebrain. Analysis of Lifr-/- mice suggests that CNTF/LIF/gp130 signaling maintains a subpopulation of GSH2+ VZ precursors, which are necessary for normal growth of the early ventral forebrain and for maintaining a gradient of VZ precursor differentiation in the lateral ganglionic eminence, as defined by GSH2, MASH1 and DLX2 expression. Furthermore, addition of exogenous CNTF to embryonic forebrain explant cultures deprived of choroid plexus-derived CNTF, was sufficient to promote a VZ differentiation gradient. In contrast to the forebrain, CNTF/LIF/gp130 signaling reduced, rather than enhanced, precursor self-renewal/expansion in the spinal cord. These results demonstrate a novel region-specific role for CNTF/LIF/gp130 signaling in the development of the germinal layers of the embryonic telencephalon.
Gregg
Christopher
C
Genes and Development Research Group, Hotchkiss Brain Institute, University of Calgary Faculty of Medicine, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.
Weiss
Samuel
S
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D011485:Protein Binding; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D053606:Receptors, OSM-LIF; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D015703:Antigens, CD; D051792:Basic Helix-Loop-Helix Proteins; D020934:Ciliary Neurotrophic Factor; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D053606:Receptors, OSM-LIF; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C088334:Distal-less homeobox proteins; C109498:Gsh2 protein, mouse; C494200:Il6st protein, mouse; C507838:Lif protein, mouse; C507841:Lifr protein, mouse