Progenitor cells of the olfactory receptor neuron lineage

The olfactory epithelium of the mouse has many properties that make it an ideal system for studying the molecular regulation of neurogenesis. We have used a combination of in vitro and in vivo approaches to identify three distinct stages of neuronal progenitors in the olfactory receptor neuron lineage. The neuronal stem cell, which is ultimately responsible for continual neuron renewal in this system, gives rise to a transit amplifying progenitor identified by its expression of a transcription factor, MASH1. The MASH1‐expressing progenitor gives rise to a second transit amplifying progenitor, the Immediate Neuronal Precursor, which is distinct from the stem cell and MASH1‐expressing progenitor, and gives rise quantitatively to olfactory receptor neurons. Regulation of progenitor cell proliferation and differentiation occurs at each of these three cell stages, and growth factors of the fibroblast growth factor (FGF) and bone morphogenetic protein (BMP) families appear to play particularly important roles in these processes. Analyses of the actions of FGFs and BMPs reveal that negative signaling plays at least as important a role as positive signaling in the regulation of olfactory neurogenesis. Microsc. Res. Tech. 58:176–188, 2002. © 2002 Wiley‐Liss, Inc.

[1]  K. Lyons,et al.  The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. , 2000, Development.

[2]  A. Calof,et al.  BMPs inhibit neurogenesis by a mechanism involving degradation of a transcription factor , 1999, Nature Neuroscience.

[3]  A. Calof,et al.  The neuronal stem cell of the olfactory epithelium. , 1998, Journal of neurobiology.

[4]  M. Vidal,et al.  Olfactory marker protein gene: its structure and olfactory neuron-specific expression in transgenic mice. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[5]  P. Graziadei,et al.  Continuous Nerve Cell Renewal in the Olfactory System , 1978 .

[6]  A. Fasolo,et al.  Expression of stathmin and SCG10 proteins in the olfactory neurogenesis during development and after lesion in the adulthood , 2001, Brain Research Bulletin.

[7]  E. Lai,et al.  Dynamics of placodal lineage development revealed by targeted transgene expression , 1999, Developmental dynamics : an official publication of the American Association of Anatomists.

[8]  R. Y. Tsai,et al.  Cloning and Functional Characterization of Roaz, a Zinc Finger Protein that Interacts with O/E-1 to Regulate Gene Expression: Implications for Olfactory Neuronal Development , 1997, The Journal of Neuroscience.

[9]  P. Graziadei,et al.  The differentiation of the olfactory placode in Xenopus laevis: A light and electron microscope study , 1983, The Journal of comparative neurology.

[10]  F. Valverde,et al.  Evidence for intrinsic development of olfactory structures in Pax‐6 mutant mice , 2000, The Journal of comparative neurology.

[11]  A. Joyner,et al.  Dynamic expression of the murine Achaete-Scute homologue Mash-1 in the developing nervous system , 1993, Mechanisms of Development.

[12]  K. Miyazono,et al.  Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis. , 1995, Endocrinology.

[13]  A. Cuschieri,et al.  The development of the olfactory mucosa in the mouse: electron microscopy. , 1975, Journal of anatomy.

[14]  K. Kaestner,et al.  Unified nomenclature for the winged helix/forkhead transcription factors. , 2000, Genes & development.

[15]  J. Mumm,et al.  Factors affecting neuronal birth and death in the mammalian olfactory epithelium. , 1996, Ciba Foundation symposium.

[16]  D. H. Matulionis Light and electron microscopic study of the degeneration and early regeneration of olfactory epithelium in the mouse. , 1976, The American journal of anatomy.

[17]  A. Simeone,et al.  A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo. , 1993, The EMBO journal.

[18]  R. Murray,et al.  Opposing effects of bone morphogenetic proteins on neuron production and survival in the olfactory receptor neuron lineage. , 2000, Development.

[19]  DM Chikaraishi,et al.  Characterization of potential precursor populations in the mouse olfactory epithelium using immunocytochemistry and autoradiography , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  K. Eto,et al.  Uchida rat (rSey): a new mutant rat with craniofacial abnormalities resembling those of the mouse Sey mutant. , 1994, Differentiation; research in biological diversity.

[21]  U. Dräger,et al.  A retinoic acid synthesizing enzyme in ventral retina and telencephalon of the embryonic mouse , 2000, Mechanisms of Development.

[22]  Sangbin Park,et al.  Interpretation of a BMP Activity Gradient in Drosophila Embryos Depends on Synergistic Signaling by Two Type I Receptors, SAX and TKV , 1998, Cell.

[23]  Anne L. Calof,et al.  Genesis of olfactory receptor neurons in vitro: Regulation of progenitor cell divisions by fibroblast growth factors , 1994, Neuron.

[24]  I. Smart Location and orientation of mitotic figures in the developing mouse olfactory epithelium. , 1971, Journal of anatomy.

[25]  David J. Anderson,et al.  Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons , 1993, Cell.

[26]  A. Calof,et al.  Analysis of neurogenesis in a mammalian neuroepithelium: Proliferation and differentiation of an olfactory neuron precursor in vitro , 1989, Neuron.

[27]  D. Gottlieb,et al.  Retinoic acid promotes neural and represses mesodermal gene expression in mouse embryonic stem cells in culture. , 1996, Biochemical and biophysical research communications.

[28]  A. Calof,et al.  Apoptosis in the neuronal lineage of the mouse olfactory epithelium: regulation in vivo and in vitro. , 1995, Developmental biology.

[29]  G. Rougon,et al.  Studies on the transmembrane disposition of the neural cell adhesion molecule N-CAM. A monoclonal antibody recognizing a cytoplasmic domain and evidence for the presence of phosphoserine residues. , 1984, European journal of biochemistry.

[30]  David J. Anderson,et al.  Identification of neurogenin, a Vertebrate Neuronal Determination Gene , 1996, Cell.

[31]  David J. Anderson,et al.  neurogenins,a Novel Family ofatonal-Related bHLH Transcription Factors, Are Putative Mammalian Neuronal Determination Genes That Reveal Progenitor Cell Heterogeneity in the Developing CNS and PNS , 1996, Molecular and Cellular Neuroscience.

[32]  G K Lewis,et al.  Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product , 1985, Molecular and cellular biology.

[33]  Stefano Stifani,et al.  The Winged-Helix Protein Brain Factor 1 Interacts with Groucho and Hes Proteins To Repress Transcription , 2001, Molecular and Cellular Biology.

[34]  A. LaMantia,et al.  Disruption of local retinoid‐mediated gene expression accompanies abnormal development in the mammalian olfactory pathway , 1997, The Journal of comparative neurology.

[35]  R. Kageyama,et al.  Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. , 2000, Development.

[36]  M. Mehler,et al.  Development of Bone Morphogenetic Protein Receptors in the Nervous System and Possible Roles in Regulating trkC Expression , 1998, The Journal of Neuroscience.

[37]  R. M. Costanzo,et al.  A quantitative analysis of changes in the olfactory epithelium following bulbectomy in hamster , 1983, The Journal of comparative neurology.

[38]  S. Carroll,et al.  The achaete‐scute complex: generation of cellular pattern and fate within the Drosophila nervous system , 1994, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[39]  E. Lai,et al.  Telencephalon-restricted expression of BF-1, a new member of the HNF-3/fork head gene family, in the developing rat brain , 1992, Neuron.

[40]  T. Saito,et al.  Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells. , 1991, Genes & development.

[41]  J. Harding,et al.  Thymidine Incorporation in the olfactory epihelium of mice: Early exponential response induced by olfactory neurectomy , 1984, Brain Research.

[42]  A. Geiser,et al.  Regulation of the promoters for the human bone morphogenetic protein 2 and 4 genes. , 2000, Gene.

[43]  C. Thaller,et al.  Temporally-regulated retinoic acid depletion produces specific neural crest, ocular and nervous system defects. , 1997, Development.

[44]  M. Lyon,et al.  Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse. , 1986, Journal of embryology and experimental morphology.

[45]  R. Palmiter,et al.  Spermatid-specific expression of protamine 1 in transgenic mice. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[46]  M. Loeffler,et al.  Stem cells: attributes, cycles, spirals, pitfalls and uncertainties. Lessons for and from the crypt. , 1990, Development.

[47]  K. Umesono,et al.  Aldehyde Dehydrogenase 6, a Cytosolic Retinaldehyde Dehydrogenase Prominently Expressed in Sensory Neuroepithelia during Development* , 2000, The Journal of Biological Chemistry.

[48]  T. Dexter,et al.  Defective ability to self-renew in vitro of highly purified primitive haematopoietic cells , 1985, Nature.

[49]  P. L. Hinds,et al.  An autoradiographic study of the mouse olfactory epithelium: Evidence for long‐lived receptors , 1984, The Anatomical record.

[50]  B. Wiedenmann,et al.  Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons , 1995, Mechanisms of Development.

[51]  J. Mumm,et al.  Factors Regulating Neurogenesis and Programmed Cell Death in Mouse Olfactory Epithelium a , 1998, Annals of the New York Academy of Sciences.

[52]  A. Joyner,et al.  Expression of growth/differentiation factor 11, a new member of the BMP/TGFβ superfamily during mouse embryogenesis , 1999, Mechanisms of Development.

[53]  A. Mackay-Sim,et al.  Cell dynamics in the adult mouse olfactory epithelium: a quantitative autoradiographic study , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[54]  In vitro analysis of neuronal progenitor cells from mouse olfactory epithelium , 1999 .

[55]  J. Kauer,et al.  Globose basal cells are neuronal progenitors in the olfactory epithelium: A lineage analysis using a replication-incompetent retrovirus , 1994, Neuron.

[56]  R. Murray,et al.  Neuronal regeneration: lessons from the olfactory system. , 1999, Seminars in cell & developmental biology.

[57]  F. Guillemot,et al.  Mash1 activates a cascade of bHLH regulators in olfactory neuron progenitors. , 1997, Development.

[58]  Fiona M. Watt,et al.  Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression , 1993, Cell.

[59]  B. Mulvaney,et al.  Regeneration of rabbit olfactory epithelium. , 1971, The American journal of anatomy.

[60]  A. Calof,et al.  Colony-forming progenitors from mouse olfactory epithelium: evidence for feedback regulation of neuron production. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[61]  G. Saunders,et al.  Mouse Small eye results from mutation in a paired-like homebox-containing gene , 1992, Nature.

[62]  Michael M. Wang,et al.  Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast , 1993, Nature.

[63]  P. Graziadei,et al.  Cell dynamics in the olfactory mucosa. , 1973, Tissue & cell.

[64]  A. LaMantia,et al.  Mesenchymal/Epithelial Induction Mediates Olfactory Pathway Formation , 2000, Neuron.

[65]  Se-Jin Lee,et al.  Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11 , 1999, Nature Genetics.

[66]  S. Carroll,et al.  Regulation of achaete-scute gene expression and sensory organ pattern formation in the Drosophila wing. , 1991, Genes & development.

[67]  P. Chambon,et al.  Embryonic retinoic acid synthesis is essential for early mouse post-implantation development , 1999, Nature Genetics.

[68]  A. Calof,et al.  Neurogenesis and cell death in olfactory epithelium. , 1996, Journal of neurobiology.

[69]  P. Chambon,et al.  Essential roles of retinoic acid signaling in interdigital apoptosis and control of BMP-7 expression in mouse autopods. , 1999, Developmental biology.

[70]  B. Hogan,et al.  Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities. , 1988, Development.

[71]  A. Farbman,et al.  Olfactory marker protein during ontogeny: immunohistochemical localization. , 1980, Developmental biology.

[72]  A. Calof,et al.  Dynamics of MASH1 Expression in Vitro and in Vivo Suggest a Non-Stem Cell Site of MASH1 Action in the Olfactory Receptor Neuron Lineage , 1995, Molecular and Cellular Neuroscience.

[73]  F. Watt,et al.  Stem cells: the generation and maintenance of cellular diversity. , 1989, Development.

[74]  R. Grainger,et al.  Altered retinoid signaling in the heads of small eye mouse embryos. , 2000, Developmental biology.

[75]  S. Ben‐Sasson,et al.  Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation , 1992, The Journal of cell biology.

[76]  David J. Anderson,et al.  Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors , 1990, Nature.

[77]  E. Ziff,et al.  Differential spatial and temporal expression of two type III intermediate filament proteins in olfactory receptor neurons , 1991, Neuron.

[78]  G. Duester,et al.  RALDH3, a retinaldehyde dehydrogenase that generates retinoic acid, is expressed in the ventral retina, otic vesicle and olfactory pit during mouse development , 2000, Mechanisms of Development.

[79]  J. Verhaagen,et al.  The expression of the growth associated protein B50/GAP43 in the olfactory system of neonatal and adult rats , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[80]  R. W. Padgett,et al.  Specificity of TGFbeta signaling is conferred by distinct type I receptors and their associated SMAD proteins in Caenorhabditis elegans. , 1999, Development.