title: ATF2 maintains a subset of neural progenitors through CBF1/Notch independent Hes-1 expression and synergistically activates the expression of Hes-1 in Notch-dependent neural progenitors.
abstract: Hes-1 and Hes-5 are downstream effectors of Notch signaling that are known to be involved in different aspects of neural stem cell proliferation and differentiation. Evidence has emerged that Hes-1 expression can be regulated by alternate signaling pathways independent of canonical Notch/CBF1 interaction. This context-dependent differential regulation of Hes-1 expression in neural progenitor gains a lot of importance as it would help in its exponential expansion without the requirement of interaction from neighboring cells during development. Here, we have clearly demonstrated the existence of a population of neural progenitors with Notch/CBF1-independent Hes-1 expression in vitro. Further analysis demonstrated the role of FGF2 in activating Hes-1 expression through the direct binding of ATF2, a JNK downstream target, on Hes-1 promoter. This raises the possibility for the existence of two distinct populations of neural progenitors - one maintained by Hes-1 expression exclusively through Notch-independent mechanism and the other mediating Hes-1 expression through both canonical Notch and FGF2-ATF2 pathway. This alternative pathway will insure a constant expression of Hes-1 even in the absence of canonical Notch intracellular domain-mediated signaling, thereby maintaining a pool of proliferating neural progenitors required during development.
authors.affiliation: Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India.
authors.forename: Rajendran
authors.initials: R
authors.lastname: Sanalkumar
authors.forename: Chandrasekharan Lalitha
authors.initials: CL
authors.lastname: Indulekha
authors.forename: Thulasi Sheela
authors.initials: TS
authors.lastname: Divya
authors.forename: Mundackal Sivaraman
authors.initials: MS
authors.lastname: Divya
authors.forename: Ruby John
authors.initials: RJ
authors.lastname: Anto
authors.forename: Balachandran
authors.initials: B
authors.lastname: Vinod
authors.forename: Sasidharan
authors.initials: S
authors.lastname: Vidyanand
authors.forename: Balusamy
authors.initials: B
authors.lastname: Jagatha
authors.forename: Shalini
authors.initials: S
authors.lastname: Venugopal
authors.forename: Jackson
authors.initials: J
authors.lastname: James
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002490:Central Nervous System / Q000196:embryology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D051698:Activating Transcription Factor 2; D051792:Basic Helix-Loop-Helix Proteins; D016222:Fibroblast Growth Factor 2; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D048031:JNK Mitogen-Activated Protein Kinases; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C497106:Atf2 protein, mouse; C489734:Hes1 protein, mouse; C497571:Rbpj protein, mouse