Developmental stage-dependent self-regulation of embryonic cortical precursor cell survival and differentiation by leukemia inhibitory factor.
Cortical precursor cells secrete soluble factors for their own survival and self-renewal. We show here that neural precursor cells isolated from embryonic rat cortices abundantly secrete leukemia inhibitory factor (LIF) and express its receptor components, gp130 and LIF receptor. LIF signaling is responsible for cortical precursor cell survival. As described previously, LIF caused astrocytic differentiation of cultured embryonic cortical precursor cells. LIF-mediated survival and astrocytic differentiation of cortical precursor cells were differentially regulated, depending on the developmental ages of embryos from which cortical precursors were isolated. LIF did not enhance the survival of cortical precursor cells isolated from later embryos (embryonic day 16, E16). Moreover, LIF-mediated astrocytic differentiation was not observed in early (E12) cortical precursors. Inhibition studies revealed that Janus-activated kinase/signal transducer and activator of transcription and phosphatidylinositol 3 kinase/Akt pathways participate in both the LIF-mediated effects. However, mitogen-activated protein kinase, another signal pathway activated by LIF, was specifically responsible for astrocytic differentiation. These findings collectively indicate that precursor cells self-regulate the sequential processes of brain development, such as early maintenance of the precursor cell population and later differentiation into astrocytes, via common LIF signaling.
Chang
M-Y
MY
Department of Biochemistry, College of Medicine, Hanyang University, Seoul 133-791, Korea.
Park
C-H
CH
Son
H
H
Lee
Y-S
YS
Lee
S-H
SH
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D019070:Cell Lineage; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology*; D050822:Cytokine Receptor gp130; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D015850:Interleukin-6 / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
D015703:Antigens, CD; C494201:Il6st protein, rat; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008024:Ligands; D008562:Membrane Glycoproteins; D050822:Cytokine Receptor gp130; D007770:L-Lactate Dehydrogenase; D019869:Phosphatidylinositol 3-Kinases; D001973:Bromodeoxyuridine