Results and problems in cell differentiation, 2002
During the development of the neocortex, cell proliferation occurs in two specialized zones adjac... more During the development of the neocortex, cell proliferation occurs in two specialized zones adjacent to the lateral ventricle. One of these zones, the ventricular zone, produces most of the neurons of the neocortex. The proliferating population that resides in the ventricular zone is a pseudostratified ventricular epithelium (PVE) that looks uniform in routine histological preparations, but is, in fact, an active and dynamically changing population. In the mouse, over the course of a 6-day period, the PVE produces approximately 95% of the neurons of the adult neocortex. During this time, the cell cycle of the PVE population lengthens from about 8 h to over 18 h and the progenitor population passes through a total of 11 cell cycles. This 6-day, 11-cell cycle period comprises the "neuronogenetic interval" (NI). At each passage through the cell cycle, the proportion of daughter cells that exit the cell cycle (Q cells) increases from 0 at the onset of the NI to 1 at the end of...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
We have analyzed clonal cell proliferation in the ventricular zone (VZ) of the early developing m... more We have analyzed clonal cell proliferation in the ventricular zone (VZ) of the early developing mouse neocortex with a replication-incompetent retrovirus encoding human placental alkaline phosphatase (AP). The retrovirus was injected into the lateral ventricles on embryonic day 11 (E11), i.e., at the onset of neuronogenesis. Three days postinjection, on E14, a total of 259 AP-labeled clones of various sizes were found in 7 fetal brains. There are approximately 7 cell cycles between E11 and E14 (), and there is a 1-2 cell cycle delay between retroviral injection and the production of a retrovirally labeled "founder" cell; thus, we estimate that the "age" of the clones was about 5-6 cell cycles. Almost one-half of the clones (48.3%) identified were pure proliferating clones containing cells only in the VZ. Another 18.5% contained both proliferating and postproliferative cells, and 33.2% contained only postproliferative cells. It was striking that over 90% of the cl...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
We have measured the amount of variation in the length of the cell cycle for cells in the pseudos... more We have measured the amount of variation in the length of the cell cycle for cells in the pseudostratified ventricular epithelium (PVE) of the developing cortex of mice on embryonic day 14. Our measurements were made in three cortical regions (i.e., the neocortex, archicortex, and periarchicortex) using three different methods: the cumulative labeling method (CLM), the percent labeled mitoses (PLM) method, and a comparison of the time needed for the PLM to ascend from 0 to 100% with the time needed for the PLM to descend from 100 to 0%. These 3 different techniques provide different perspectives on the cytokinetic parameters. Theoretically, CLM gives an estimate for a maximum value of the total length of the cell cycle (TC), whereas PLM gives an estimate of a minimum value of TC. The difference between these two estimates indicates that the range for TC is +/-1% of the mean TC for periarchicortex, +/-7% for neocortex, and +/-8% for archicortex. This was confirmed by a lengthening of...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1996
Neurons of neocortical layers II-VI in the dorsomedial cortex of the mouse arise in the pseudostr... more Neurons of neocortical layers II-VI in the dorsomedial cortex of the mouse arise in the pseudostratified ventricular epithelium (PVE) through 11 cell cycles over the six embryonic days 11-17 (E11-E17). The present experiments measure the proportion of daughter cells that leave the cycle (quiescent or Q fraction or Q) during a single cell cycle and the complementary proportion that continues to proliferate (proliferative or P fraction or P; P = 1 - Q). Q and P for the PVE become 0.5 in the course of the eighth cycle, occurring on E14, and Q rises to approximately 0.8 (and P falls to approximately 0.2) in the course of the 10th cycle occurring on E16. This indicates that early in neuronogenesis, neurons are produced relatively slowly and the PVE expands rapidly but that the reverse happens in the final phase of neuronogenesis. The present analysis completes a cycle of analyses that have determined the four fundamental parameters of cell proliferation: growth fraction, lengths of cell ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1996
Neocortical neuronogenesis occurs in the pseudostratified ventricular epithelium (PVE) where nucl... more Neocortical neuronogenesis occurs in the pseudostratified ventricular epithelium (PVE) where nuclei of proliferative cells undergo interkinetic nuclear movement. A fraction of daughter cells exits the cell cycle as neurons (the quiescent, or Q, fraction), whereas a complementary fraction remains in the cell cycle (the proliferative, or P, fraction). By means of sequential thymidine and bromodeoxyuridine injections in mouse on embryonic day 14, we have monitored the proliferative and post-mitotic migratory behaviors of 1 and 2 hr cohorts of PVE cells defined by the injection protocols. Soon after mitosis, the Q fraction partitions into a rapidly exiting (up to 50 microns/hr) subpopulation (Qr) and a more slowly exiting (6 microns/hr) subpopulation (Qs). Qr and Qs are separated as two distributions on exit from the ventricular zone with an interpeak distance of approximately 40 microns. Cells in Qr and Qs migrate through the intermediate zone with no significant change in the interpea...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1993
Cytogenesis is the critical determinant of the total number of neurons that contribute to the for... more Cytogenesis is the critical determinant of the total number of neurons that contribute to the formation of the cerebral cortex and the rate at which the cells are produced. Two distinct cell populations constitute the proliferative population, a pseudostratified ventricular epithelium (PVE) lying within the ventricular zone (VZ) at the margin of the ventricle, and a secondary proliferative population that is intermixed with the PVE within the VZ but also is distributed through the overlying subventricular and intermediate zones of the cerebral wall. The present analysis, based upon cumulative S-phase labeling of the proliferative cells with 5-bromo-2'-deoxyuridine, is principally concerned with the PVE of the gestational-day-14 (E14) murine cerebral wall. It has immediate but also more far reaching general objectives. The most immediate objective, essential to the design and interpretation of later experiments, is to provide estimates of critical parameters of cytogenesis for th...
The human central nervous system (CNS) is the most complex organ in the body, and the processes i... more The human central nervous system (CNS) is the most complex organ in the body, and the processes involved in its development are commensurately complex. A basic understanding of these processes is an essential part of understanding how disruptions of development that result in ...
increased Q is associated with a commensurate increase in the proportion of exiting cells that is... more increased Q is associated with a commensurate increase in the proportion of exiting cells that is directed to superficial layers. We conclude that mechanisms that govern specification of neocortical neuronal laminar destination are coordinately regulated with mech- anisms that regulate Q and are independent of mechanisms regulatory to cell cycle duration. Moreover, they operate prior to postproliferative mechanisms necessary to
Character displacement resulting from interspecific competition has been extremely difficult to d... more Character displacement resulting from interspecific competition has been extremely difficult to demonstrate. The problem was addressed with a study of Darwin's ground finches (Geospiza). Beak sizes of populations of G. fortis and G. fuliginosa in sympatry and allopatry were compared by a procedure that controls for any possible effects on morphology of variation among locations in food supply. The results provide strong evidence for character displacement. Measurement of natural selection in a population of G. fortis on an island (Daphne) lacking a resident population of G. fuliginosa shows how exploitation of G. fuliginosa foods affects the differential survival of G. fortis phenotypes.
11 Quantitative Analysis of Fetal and Adult Neurogenesis: Regulation of Neuron Number RICHARD S. ... more 11 Quantitative Analysis of Fetal and Adult Neurogenesis: Regulation of Neuron Number RICHARD S. NOWAKOWSKI AND NANCY L. HAYES ABSTRACT The proliferative populations in fetal and adult brain differ in fundamental ways. In both, the productive potential is pro-portional to ...
Page 62. 3 Neocortical neuronogenesis: the G1 restriction point as master integrative mechanism V... more Page 62. 3 Neocortical neuronogenesis: the G1 restriction point as master integrative mechanism Verne S. Caviness, Jr. ... Journal ofNeuroscience, 17, 2079-87. Page 79. Neocortical neurogenesis Cavanagh,]., Mione, M., Pappas, I. & Parnavelas, J.(1997). ...
Results and problems in cell differentiation, 2002
During the development of the neocortex, cell proliferation occurs in two specialized zones adjac... more During the development of the neocortex, cell proliferation occurs in two specialized zones adjacent to the lateral ventricle. One of these zones, the ventricular zone, produces most of the neurons of the neocortex. The proliferating population that resides in the ventricular zone is a pseudostratified ventricular epithelium (PVE) that looks uniform in routine histological preparations, but is, in fact, an active and dynamically changing population. In the mouse, over the course of a 6-day period, the PVE produces approximately 95% of the neurons of the adult neocortex. During this time, the cell cycle of the PVE population lengthens from about 8 h to over 18 h and the progenitor population passes through a total of 11 cell cycles. This 6-day, 11-cell cycle period comprises the "neuronogenetic interval" (NI). At each passage through the cell cycle, the proportion of daughter cells that exit the cell cycle (Q cells) increases from 0 at the onset of the NI to 1 at the end of...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
We have analyzed clonal cell proliferation in the ventricular zone (VZ) of the early developing m... more We have analyzed clonal cell proliferation in the ventricular zone (VZ) of the early developing mouse neocortex with a replication-incompetent retrovirus encoding human placental alkaline phosphatase (AP). The retrovirus was injected into the lateral ventricles on embryonic day 11 (E11), i.e., at the onset of neuronogenesis. Three days postinjection, on E14, a total of 259 AP-labeled clones of various sizes were found in 7 fetal brains. There are approximately 7 cell cycles between E11 and E14 (), and there is a 1-2 cell cycle delay between retroviral injection and the production of a retrovirally labeled "founder" cell; thus, we estimate that the "age" of the clones was about 5-6 cell cycles. Almost one-half of the clones (48.3%) identified were pure proliferating clones containing cells only in the VZ. Another 18.5% contained both proliferating and postproliferative cells, and 33.2% contained only postproliferative cells. It was striking that over 90% of the cl...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1997
We have measured the amount of variation in the length of the cell cycle for cells in the pseudos... more We have measured the amount of variation in the length of the cell cycle for cells in the pseudostratified ventricular epithelium (PVE) of the developing cortex of mice on embryonic day 14. Our measurements were made in three cortical regions (i.e., the neocortex, archicortex, and periarchicortex) using three different methods: the cumulative labeling method (CLM), the percent labeled mitoses (PLM) method, and a comparison of the time needed for the PLM to ascend from 0 to 100% with the time needed for the PLM to descend from 100 to 0%. These 3 different techniques provide different perspectives on the cytokinetic parameters. Theoretically, CLM gives an estimate for a maximum value of the total length of the cell cycle (TC), whereas PLM gives an estimate of a minimum value of TC. The difference between these two estimates indicates that the range for TC is +/-1% of the mean TC for periarchicortex, +/-7% for neocortex, and +/-8% for archicortex. This was confirmed by a lengthening of...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1996
Neurons of neocortical layers II-VI in the dorsomedial cortex of the mouse arise in the pseudostr... more Neurons of neocortical layers II-VI in the dorsomedial cortex of the mouse arise in the pseudostratified ventricular epithelium (PVE) through 11 cell cycles over the six embryonic days 11-17 (E11-E17). The present experiments measure the proportion of daughter cells that leave the cycle (quiescent or Q fraction or Q) during a single cell cycle and the complementary proportion that continues to proliferate (proliferative or P fraction or P; P = 1 - Q). Q and P for the PVE become 0.5 in the course of the eighth cycle, occurring on E14, and Q rises to approximately 0.8 (and P falls to approximately 0.2) in the course of the 10th cycle occurring on E16. This indicates that early in neuronogenesis, neurons are produced relatively slowly and the PVE expands rapidly but that the reverse happens in the final phase of neuronogenesis. The present analysis completes a cycle of analyses that have determined the four fundamental parameters of cell proliferation: growth fraction, lengths of cell ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 1996
Neocortical neuronogenesis occurs in the pseudostratified ventricular epithelium (PVE) where nucl... more Neocortical neuronogenesis occurs in the pseudostratified ventricular epithelium (PVE) where nuclei of proliferative cells undergo interkinetic nuclear movement. A fraction of daughter cells exits the cell cycle as neurons (the quiescent, or Q, fraction), whereas a complementary fraction remains in the cell cycle (the proliferative, or P, fraction). By means of sequential thymidine and bromodeoxyuridine injections in mouse on embryonic day 14, we have monitored the proliferative and post-mitotic migratory behaviors of 1 and 2 hr cohorts of PVE cells defined by the injection protocols. Soon after mitosis, the Q fraction partitions into a rapidly exiting (up to 50 microns/hr) subpopulation (Qr) and a more slowly exiting (6 microns/hr) subpopulation (Qs). Qr and Qs are separated as two distributions on exit from the ventricular zone with an interpeak distance of approximately 40 microns. Cells in Qr and Qs migrate through the intermediate zone with no significant change in the interpea...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1993
Cytogenesis is the critical determinant of the total number of neurons that contribute to the for... more Cytogenesis is the critical determinant of the total number of neurons that contribute to the formation of the cerebral cortex and the rate at which the cells are produced. Two distinct cell populations constitute the proliferative population, a pseudostratified ventricular epithelium (PVE) lying within the ventricular zone (VZ) at the margin of the ventricle, and a secondary proliferative population that is intermixed with the PVE within the VZ but also is distributed through the overlying subventricular and intermediate zones of the cerebral wall. The present analysis, based upon cumulative S-phase labeling of the proliferative cells with 5-bromo-2'-deoxyuridine, is principally concerned with the PVE of the gestational-day-14 (E14) murine cerebral wall. It has immediate but also more far reaching general objectives. The most immediate objective, essential to the design and interpretation of later experiments, is to provide estimates of critical parameters of cytogenesis for th...
The human central nervous system (CNS) is the most complex organ in the body, and the processes i... more The human central nervous system (CNS) is the most complex organ in the body, and the processes involved in its development are commensurately complex. A basic understanding of these processes is an essential part of understanding how disruptions of development that result in ...
increased Q is associated with a commensurate increase in the proportion of exiting cells that is... more increased Q is associated with a commensurate increase in the proportion of exiting cells that is directed to superficial layers. We conclude that mechanisms that govern specification of neocortical neuronal laminar destination are coordinately regulated with mech- anisms that regulate Q and are independent of mechanisms regulatory to cell cycle duration. Moreover, they operate prior to postproliferative mechanisms necessary to
Character displacement resulting from interspecific competition has been extremely difficult to d... more Character displacement resulting from interspecific competition has been extremely difficult to demonstrate. The problem was addressed with a study of Darwin's ground finches (Geospiza). Beak sizes of populations of G. fortis and G. fuliginosa in sympatry and allopatry were compared by a procedure that controls for any possible effects on morphology of variation among locations in food supply. The results provide strong evidence for character displacement. Measurement of natural selection in a population of G. fortis on an island (Daphne) lacking a resident population of G. fuliginosa shows how exploitation of G. fuliginosa foods affects the differential survival of G. fortis phenotypes.
11 Quantitative Analysis of Fetal and Adult Neurogenesis: Regulation of Neuron Number RICHARD S. ... more 11 Quantitative Analysis of Fetal and Adult Neurogenesis: Regulation of Neuron Number RICHARD S. NOWAKOWSKI AND NANCY L. HAYES ABSTRACT The proliferative populations in fetal and adult brain differ in fundamental ways. In both, the productive potential is pro-portional to ...
Page 62. 3 Neocortical neuronogenesis: the G1 restriction point as master integrative mechanism V... more Page 62. 3 Neocortical neuronogenesis: the G1 restriction point as master integrative mechanism Verne S. Caviness, Jr. ... Journal ofNeuroscience, 17, 2079-87. Page 79. Neocortical neurogenesis Cavanagh,]., Mione, M., Pappas, I. & Parnavelas, J.(1997). ...
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