Id2 is required for specification of dopaminergic neurons during adult olfactory neurogenesis.
Understanding the biology of adult neural stem cells has important implications for nervous system development and may contribute to our understanding of neurodegenerative disorders and their treatment. We have characterized the process of olfactory neurogenesis in adult mice lacking inhibitor of DNA binding 2(-/-) (Id2(-/-)). We found a diminished olfactory bulb containing reduced numbers of granular and periglomerular neurons with a distinct paucity of dopaminergic periglomerular neurons. While no deficiency of the stem cell compartment was detectable, migrating neuroblasts in Id2(-/-) mutant mice prematurely undergo astroglial differentiation within a disorganized rostral migratory stream. Further, when evaluated in vitro loss of Id2 results in decreased proliferation of neural progenitors and decreased expression of the Hes1 and Ascl1 (Mash1) transcription factors, known mediators of neuronal differentiation. These data support a novel role for sustained Id2 expression in migrating neural progenitors mediating olfactory dopaminergic neuronal differentiation in adult animals.
Havrda
Matthew C
MC
Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA. Matthew.C.Havrda@Dartmouth.edu
Harris
Brent T
BT
Mantani
Akio
A
Ward
Nora M
NM
Paolella
Brenton R
BR
Cuzon
Verginia C
VC
Yeh
Hermes H
HH
Israel
Mark A
MA
D053687:Adult Stem Cells / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D004192:Discrimination, Psychological / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology* / Q000254:growth & development; D009833:Olfactory Pathways / Q000166:cytology / Q000502:physiology; D012903:Smell / Q000235:genetics; D018709:Statistics, Nonparametric; D000072056:Transcription Factor HES-1; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004298:Dopamine; D005904:Glial Fibrillary Acidic Protein; D018398:Homeodomain Proteins; D051797:Inhibitor of Differentiation Protein 2; D000072056:Transcription Factor HES-1; D014446:Tyrosine 3-Monooxygenase; C499317:Ascl1 protein, mouse; C489734:Hes1 protein, mouse; C497452:Idb2 protein, mouse