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.
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.
Sanalkumar
Rajendran
R
Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India.
Indulekha
Chandrasekharan Lalitha
CL
Divya
Thulasi Sheela
TS
Divya
Mundackal Sivaraman
MS
Anto
Ruby John
RJ
Vinod
Balachandran
B
Vidyanand
Sasidharan
S
Jagatha
Balusamy
B
Venugopal
Shalini
S
James
Jackson
J
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
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