Growth cones, dying axons, and developmental fluctuations in the fiber population of the cat's optic nerve

Robert Williams, Michael J. Bastiani, Barry Lia, Leo M. Chalupa

Research output: Contribution to journalArticle

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Abstract

We have studied the rise and fall in the number of axons in the optic nerve of fetal and neonatal cats in relation to changes in the ultrastructure of fibers, and in particular, to the characteristics and spatiotemporal distribution of growth cones and necrotic axons. Axons of retinal ganglion cells start to grow through the optic nerve on the 19th day of embryonic development (E‐19). As early as E‐23 there are 8,000 fibers in the nerve close to the eye. Fibers are added to the nerve at a rate of approximately 50,000 per day from E‐28 until E‐39–the age at which the peak population of 600,000‐700,000 axons is reached. Thereafter, the number decreases rapidly: About 400,000 axons are lost between E‐39 and E‐53. In contrast, from E‐56 until the second week after birth the number of axons decreases at a slow rate. Even as late as postnatal day 12 (P‐12) the nerve contains an excess of up to 100,000 fibers. The final number of fibers–140,000‐165,000–is reached by the sixth week after birth. Growth cones of retinal ganglion cells are present in the optic nerve from E‐19 until E‐39. At E‐19 and E‐23 they have comparatively simple shapes but in older fetuses they are larger and their shapes are more elaborate. As early as E‐28 many growth cones have lamellipodia that extend outward from the core region as far as 10 μm. These sheetlike processes are insinuated between bundles of axons and commonly contact 10 to 20 neighboring fibers in single transverse sections. At E‐28 growth cones make up 2.0% of the fiber population; at E‐33 they make up about 1.0%; from E‐36 to E‐39 they make up only 0.3% of the population. Virtually none are present in the midorhital part of the nerve on or after E‐44. At all ages growth cones are more common at the periphery of the nerve than at its center. This central‐to‐peripheral gradient increases with age: at E‐28 the density of growth cones is two times greater at the edge than at the center but by E‐39 the density is four to five times greater. Necrotic fibers are observed as early as E‐28 in all parts of the nerve. Their axoplasm is dark and mottled and often contains dense vesiculated structures. From E‐28 to E‐39 an average of about 0.15% of all fibers are obviously necrotic, whereas during the most acute phase of fiber elimination–between E‐44 and E‐48–up to 0.4% are necrotic. Thereafter, their incidence is typically under 0.05%. Necrotic axons are scattered throughout the nerve. We estimate that the time required to clear away the debris of single axons is short‐on the order of 1 hour–and on the basis of this estimate, we conclude that between 100,000 and 200,000 axons are lost even before the peak population of 700,000 is reached. Taking into account the early loss of fibers, we estimate that a total of 800,000‐900,000 retinal ganglion cell axons are produced in the fetal cat over a 20‐day period from E‐19 to E‐39. Remarkably, only 20% survive to adulthood. The loss of fibers begins a few days before axons penetrate the thalamus (Shatz, '83), about 2 weeks before the onset of synaptogenesis in the dorsal lateral geniculate nucleus (Shatz and Kirkwood, '84), and more than 3 weeks before the segregation of retinal projections (Williams and Chalupa, '82,'83a; Shatz, '83; Chalupa and Williams, '84). The elimination of axons also persists long after the segregation of axon arbors from right and left eyes is complete, and as many as 100,000 axons are lost even after eye opening during a 1‐month period when retinal arbors are still undergoing remarkable changes in shape and connectivity (Mason, '82a,b; Sur et al, '84).

Original languageEnglish (US)
Pages (from-to)32-69
Number of pages38
JournalJournal of Comparative Neurology
Volume246
Issue number1
DOIs
StatePublished - Jan 1 1986

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Growth Cones
Optic Nerve
Axons
Cats
Population
Retinal Ganglion Cells
Parturition
Geniculate Bodies
Pseudopodia
Thalamus
Nerve Fibers

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Growth cones, dying axons, and developmental fluctuations in the fiber population of the cat's optic nerve. / Williams, Robert; Bastiani, Michael J.; Lia, Barry; Chalupa, Leo M.

In: Journal of Comparative Neurology, Vol. 246, No. 1, 01.01.1986, p. 32-69.

Research output: Contribution to journalArticle

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abstract = "We have studied the rise and fall in the number of axons in the optic nerve of fetal and neonatal cats in relation to changes in the ultrastructure of fibers, and in particular, to the characteristics and spatiotemporal distribution of growth cones and necrotic axons. Axons of retinal ganglion cells start to grow through the optic nerve on the 19th day of embryonic development (E‐19). As early as E‐23 there are 8,000 fibers in the nerve close to the eye. Fibers are added to the nerve at a rate of approximately 50,000 per day from E‐28 until E‐39–the age at which the peak population of 600,000‐700,000 axons is reached. Thereafter, the number decreases rapidly: About 400,000 axons are lost between E‐39 and E‐53. In contrast, from E‐56 until the second week after birth the number of axons decreases at a slow rate. Even as late as postnatal day 12 (P‐12) the nerve contains an excess of up to 100,000 fibers. The final number of fibers–140,000‐165,000–is reached by the sixth week after birth. Growth cones of retinal ganglion cells are present in the optic nerve from E‐19 until E‐39. At E‐19 and E‐23 they have comparatively simple shapes but in older fetuses they are larger and their shapes are more elaborate. As early as E‐28 many growth cones have lamellipodia that extend outward from the core region as far as 10 μm. These sheetlike processes are insinuated between bundles of axons and commonly contact 10 to 20 neighboring fibers in single transverse sections. At E‐28 growth cones make up 2.0{\%} of the fiber population; at E‐33 they make up about 1.0{\%}; from E‐36 to E‐39 they make up only 0.3{\%} of the population. Virtually none are present in the midorhital part of the nerve on or after E‐44. At all ages growth cones are more common at the periphery of the nerve than at its center. This central‐to‐peripheral gradient increases with age: at E‐28 the density of growth cones is two times greater at the edge than at the center but by E‐39 the density is four to five times greater. Necrotic fibers are observed as early as E‐28 in all parts of the nerve. Their axoplasm is dark and mottled and often contains dense vesiculated structures. From E‐28 to E‐39 an average of about 0.15{\%} of all fibers are obviously necrotic, whereas during the most acute phase of fiber elimination–between E‐44 and E‐48–up to 0.4{\%} are necrotic. Thereafter, their incidence is typically under 0.05{\%}. Necrotic axons are scattered throughout the nerve. We estimate that the time required to clear away the debris of single axons is short‐on the order of 1 hour–and on the basis of this estimate, we conclude that between 100,000 and 200,000 axons are lost even before the peak population of 700,000 is reached. Taking into account the early loss of fibers, we estimate that a total of 800,000‐900,000 retinal ganglion cell axons are produced in the fetal cat over a 20‐day period from E‐19 to E‐39. Remarkably, only 20{\%} survive to adulthood. The loss of fibers begins a few days before axons penetrate the thalamus (Shatz, '83), about 2 weeks before the onset of synaptogenesis in the dorsal lateral geniculate nucleus (Shatz and Kirkwood, '84), and more than 3 weeks before the segregation of retinal projections (Williams and Chalupa, '82,'83a; Shatz, '83; Chalupa and Williams, '84). The elimination of axons also persists long after the segregation of axon arbors from right and left eyes is complete, and as many as 100,000 axons are lost even after eye opening during a 1‐month period when retinal arbors are still undergoing remarkable changes in shape and connectivity (Mason, '82a,b; Sur et al, '84).",
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N2 - We have studied the rise and fall in the number of axons in the optic nerve of fetal and neonatal cats in relation to changes in the ultrastructure of fibers, and in particular, to the characteristics and spatiotemporal distribution of growth cones and necrotic axons. Axons of retinal ganglion cells start to grow through the optic nerve on the 19th day of embryonic development (E‐19). As early as E‐23 there are 8,000 fibers in the nerve close to the eye. Fibers are added to the nerve at a rate of approximately 50,000 per day from E‐28 until E‐39–the age at which the peak population of 600,000‐700,000 axons is reached. Thereafter, the number decreases rapidly: About 400,000 axons are lost between E‐39 and E‐53. In contrast, from E‐56 until the second week after birth the number of axons decreases at a slow rate. Even as late as postnatal day 12 (P‐12) the nerve contains an excess of up to 100,000 fibers. The final number of fibers–140,000‐165,000–is reached by the sixth week after birth. Growth cones of retinal ganglion cells are present in the optic nerve from E‐19 until E‐39. At E‐19 and E‐23 they have comparatively simple shapes but in older fetuses they are larger and their shapes are more elaborate. As early as E‐28 many growth cones have lamellipodia that extend outward from the core region as far as 10 μm. These sheetlike processes are insinuated between bundles of axons and commonly contact 10 to 20 neighboring fibers in single transverse sections. At E‐28 growth cones make up 2.0% of the fiber population; at E‐33 they make up about 1.0%; from E‐36 to E‐39 they make up only 0.3% of the population. Virtually none are present in the midorhital part of the nerve on or after E‐44. At all ages growth cones are more common at the periphery of the nerve than at its center. This central‐to‐peripheral gradient increases with age: at E‐28 the density of growth cones is two times greater at the edge than at the center but by E‐39 the density is four to five times greater. Necrotic fibers are observed as early as E‐28 in all parts of the nerve. Their axoplasm is dark and mottled and often contains dense vesiculated structures. From E‐28 to E‐39 an average of about 0.15% of all fibers are obviously necrotic, whereas during the most acute phase of fiber elimination–between E‐44 and E‐48–up to 0.4% are necrotic. Thereafter, their incidence is typically under 0.05%. Necrotic axons are scattered throughout the nerve. We estimate that the time required to clear away the debris of single axons is short‐on the order of 1 hour–and on the basis of this estimate, we conclude that between 100,000 and 200,000 axons are lost even before the peak population of 700,000 is reached. Taking into account the early loss of fibers, we estimate that a total of 800,000‐900,000 retinal ganglion cell axons are produced in the fetal cat over a 20‐day period from E‐19 to E‐39. Remarkably, only 20% survive to adulthood. The loss of fibers begins a few days before axons penetrate the thalamus (Shatz, '83), about 2 weeks before the onset of synaptogenesis in the dorsal lateral geniculate nucleus (Shatz and Kirkwood, '84), and more than 3 weeks before the segregation of retinal projections (Williams and Chalupa, '82,'83a; Shatz, '83; Chalupa and Williams, '84). The elimination of axons also persists long after the segregation of axon arbors from right and left eyes is complete, and as many as 100,000 axons are lost even after eye opening during a 1‐month period when retinal arbors are still undergoing remarkable changes in shape and connectivity (Mason, '82a,b; Sur et al, '84).

AB - We have studied the rise and fall in the number of axons in the optic nerve of fetal and neonatal cats in relation to changes in the ultrastructure of fibers, and in particular, to the characteristics and spatiotemporal distribution of growth cones and necrotic axons. Axons of retinal ganglion cells start to grow through the optic nerve on the 19th day of embryonic development (E‐19). As early as E‐23 there are 8,000 fibers in the nerve close to the eye. Fibers are added to the nerve at a rate of approximately 50,000 per day from E‐28 until E‐39–the age at which the peak population of 600,000‐700,000 axons is reached. Thereafter, the number decreases rapidly: About 400,000 axons are lost between E‐39 and E‐53. In contrast, from E‐56 until the second week after birth the number of axons decreases at a slow rate. Even as late as postnatal day 12 (P‐12) the nerve contains an excess of up to 100,000 fibers. The final number of fibers–140,000‐165,000–is reached by the sixth week after birth. Growth cones of retinal ganglion cells are present in the optic nerve from E‐19 until E‐39. At E‐19 and E‐23 they have comparatively simple shapes but in older fetuses they are larger and their shapes are more elaborate. As early as E‐28 many growth cones have lamellipodia that extend outward from the core region as far as 10 μm. These sheetlike processes are insinuated between bundles of axons and commonly contact 10 to 20 neighboring fibers in single transverse sections. At E‐28 growth cones make up 2.0% of the fiber population; at E‐33 they make up about 1.0%; from E‐36 to E‐39 they make up only 0.3% of the population. Virtually none are present in the midorhital part of the nerve on or after E‐44. At all ages growth cones are more common at the periphery of the nerve than at its center. This central‐to‐peripheral gradient increases with age: at E‐28 the density of growth cones is two times greater at the edge than at the center but by E‐39 the density is four to five times greater. Necrotic fibers are observed as early as E‐28 in all parts of the nerve. Their axoplasm is dark and mottled and often contains dense vesiculated structures. From E‐28 to E‐39 an average of about 0.15% of all fibers are obviously necrotic, whereas during the most acute phase of fiber elimination–between E‐44 and E‐48–up to 0.4% are necrotic. Thereafter, their incidence is typically under 0.05%. Necrotic axons are scattered throughout the nerve. We estimate that the time required to clear away the debris of single axons is short‐on the order of 1 hour–and on the basis of this estimate, we conclude that between 100,000 and 200,000 axons are lost even before the peak population of 700,000 is reached. Taking into account the early loss of fibers, we estimate that a total of 800,000‐900,000 retinal ganglion cell axons are produced in the fetal cat over a 20‐day period from E‐19 to E‐39. Remarkably, only 20% survive to adulthood. The loss of fibers begins a few days before axons penetrate the thalamus (Shatz, '83), about 2 weeks before the onset of synaptogenesis in the dorsal lateral geniculate nucleus (Shatz and Kirkwood, '84), and more than 3 weeks before the segregation of retinal projections (Williams and Chalupa, '82,'83a; Shatz, '83; Chalupa and Williams, '84). The elimination of axons also persists long after the segregation of axon arbors from right and left eyes is complete, and as many as 100,000 axons are lost even after eye opening during a 1‐month period when retinal arbors are still undergoing remarkable changes in shape and connectivity (Mason, '82a,b; Sur et al, '84).

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