Brain factor-1 controls the proliferation and differentiation of neocortical progenitor cells through independent mechanisms.
The winged helix gene Brain factor-1 (BF1) has a pleiotropic role in the development of the cerebral hemispheres of the brain. Mice lacking BF1 have defects in the morphogenesis of the structures of the dorsal telencephalon (e.g., neocortex) and the ventral telencephalon (e.g., the basal ganglia). This study focuses on the functions of BF1 in the dorsal telencephalon. We showed previously that telencephalic progenitor cells lacking BF1 differentiate into neurons prematurely. Here, we demonstrate that the loss of BF1 also results in an early lengthening of the cell cycle in neocortical progenitors. To investigate the mechanisms by which BF1 regulates progenitor cell proliferation and differentiation in the developing brain, we have replaced the endogenous BF1 protein with a DNA binding defective form of BF1 in mice, BF1(NHAA). The BF1(NHAA) protein restores the growth of the dorsal telencephalon, by improving the proliferation of progenitor cells. However, the BF1(NHAA) protein does not correct the early neuronal differentiation associated with the loss of BF1. In contrast, replacement of endogenous BF1 with wild-type BF1 corrects the defects in both the proliferation and differentiation of neocortical progenitors. These results demonstrate that BF1 controls progenitor cell proliferation and differentiation in the neocortex through distinct DNA binding-independent and binding-dependent mechanisms.
Hanashima
Carina
C
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Shen
Lijian
L
Li
Suzanne C
SC
Lai
Eseng
E
D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D051379:Mice; D008818:Mice, Neurologic Mutants; D019579:Neocortex / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013687:Telencephalon / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C489562:Foxd1 protein, mouse; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D004247:DNA; D001973:Bromodeoxyuridine