Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells.
In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.
Sawada
K
K
Department of Neuropsychiatry, Kochi Medical School, Kohasu, Okoh-cho, Nankoku City, Kochi 783-8505, Japan.
Konishi
Y
Y
Tominaga
M
M
Watanabe
Y
Y
Hirano
J
J
Inoue
S
S
Kageyama
R
R
Blum
M
M
Tominaga
A
A
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D051956:Goosecoid Protein; D018398:Homeodomain Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000032:analysis; D016296:Mutagenesis / Q000502:physiology; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D016900:Neurofilament Proteins / Q000235:genetics; D009474:Neurons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics; D016196:S Phase / Q000187:drug effects / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D051956:Goosecoid Protein; D018398:Homeodomain Proteins; D008869:Microtubule-Associated Proteins; D020932:Nerve Growth Factor; D016900:Neurofilament Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C497994:Gsc protein, rat; C489735:Hes1 protein, rat; C085284:microtubule-associated protein 1B; C044882:neurofilament protein L