Limits...
Intraflagellar transport is essential for mammalian spermiogenesis but is absent in mature sperm.

San Agustin JT, Pazour GJ, Witman GB - Mol. Biol. Cell (2015)

Bottom Line: This mutation is highly disruptive to ciliary assembly in other organs.Ift88(-/-) mice are completely sterile.The short flagella rarely have axonemes but assemble ectopic microtubules and outer dense fibers and accumulate improperly assembled fibrous sheath proteins.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.

No MeSH data available.


Related in: MedlinePlus

Key steps in the development of the mouse sperm flagellum during spermiogenesis. Adapted from Russell et al. (1990). Boxed events were determined from our experiments unless stated otherwise. Steps 1–8 are round spermatids, before the beginning of nuclear condensation and elongation in step 9. Based on the rat (Leblond and Clermont, 1952; Russell et al., 1990), the axoneme is assembled to full length in step 2-3. Assembly of outer dense fibers (ODFs) around the axoneme begins at the proximal end of the midpiece of step 8 spermatids; the process is completed just before the mature sperm is released into the lumen of the seminiferous tubule. Fibrous sheath (FS) assembly begins at the distal end of the principal piece of step 2 rat spermatids with the formation of fibrous sheath columns along the axonemal doublet microtubules 3 and 8; a similar event is presumed to take place in step 2-3 mouse spermatids. Assembly of fibrous sheath ribs on the columns starts in step 10 spermatids and is complete in step 13 spermatids. The manchette is first seen in step 8 spermatids and disappears by step 14. The annulus slides distally down the axoneme to its final location between the distal end of the midpiece and the proximal end of the principal piece when step 15 is reached (Kwitny et al., 2010). The mitochondria then condense along the length of the midpiece.
© Copyright Policy - creative-commons
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4666132&req=5

Figure 2: Key steps in the development of the mouse sperm flagellum during spermiogenesis. Adapted from Russell et al. (1990). Boxed events were determined from our experiments unless stated otherwise. Steps 1–8 are round spermatids, before the beginning of nuclear condensation and elongation in step 9. Based on the rat (Leblond and Clermont, 1952; Russell et al., 1990), the axoneme is assembled to full length in step 2-3. Assembly of outer dense fibers (ODFs) around the axoneme begins at the proximal end of the midpiece of step 8 spermatids; the process is completed just before the mature sperm is released into the lumen of the seminiferous tubule. Fibrous sheath (FS) assembly begins at the distal end of the principal piece of step 2 rat spermatids with the formation of fibrous sheath columns along the axonemal doublet microtubules 3 and 8; a similar event is presumed to take place in step 2-3 mouse spermatids. Assembly of fibrous sheath ribs on the columns starts in step 10 spermatids and is complete in step 13 spermatids. The manchette is first seen in step 8 spermatids and disappears by step 14. The annulus slides distally down the axoneme to its final location between the distal end of the midpiece and the proximal end of the principal piece when step 15 is reached (Kwitny et al., 2010). The mitochondria then condense along the length of the midpiece.

Mentions: Previously spermatogenesis was carefully examined in the rat (Leblond and Clermont, 1952; Russell et al., 1990). Although mouse spermatogenesis has not been so thoroughly characterized, Russell et al. (1990) built on the existing literature for both rat and mouse to provide a very useful description of the events during mouse spermiogenesis. To assist in interpreting the effects of the Ift88 mutation on sperm development, we have combined the diagrams of Russell et al. (1990) with our observations to order the key steps of flagellar development during mouse spermiogenesis (Figure 2). Spermatogenesis, or the development of sperm, begins with germ cells dividing and undergoing meiosis to generate spermatids. These develop into spermatozoa through the process of spermiogenesis. Spermiogenesis can be divided into 16 steps (Arabic numerals in Figure 2), which occur in synchronous waves along the seminiferous tubules of the testes. A section through a tubule will reveal germ cells at three or four stages of spermatogenesis, with one or two of these being spermiogenic. The more mature cells are organized in a band near the central lumen, and progressively less mature cells are localized in zones progressively closer to the outer surface or boundary of the tubule. Twelve distinct morphologies of the tubule (called stages and written in Roman numerals) can be distinguished by the steps of development occurring in a given tubule cross-section. For example, a section through a stage IV tubule will reveal step 15 spermatids with their flagella extending into the lumen of the tubule and step 4 spermatids located in a band between the lumen and the outer surface of the tubule. Spermiogenesis begins at step 1 with the appearance of haploid, round spermatids arising from two sequential meiotic divisions of the diplotene spermatocytes. During step 2-3, the 9 + 2 flagellar axoneme begins to elongate from a basal body located just below the plasma membrane and reaches nearly full length (Irons and Clermont, 1982). At this time, the axoneme is tightly surrounded by the flagellar membrane, which is continuous with cellular plasma membrane. Also during step 2-3, the precursors or “anlagen” of the fibrous sheath columns begin to form at the distal end of the flagellum (Sakai et al., 1986). The fibrous sheath columns and ribs subsequently are assembled in a distal-to-proximal direction in what will become the principal piece of the sperm (Irons and Clermont, 1982). Between steps 6 and 7 (Russell et al., 1990), the basal body with attached axoneme migrates inward to the nucleus and pulls the plasma membrane along with it to create an invagination of the plasma membrane that now surrounds the proximal portion of the flagellum. At step 8, the outer dense fibers begin to form at the proximal end of the axoneme. The fibers assemble along the axonemal doublet microtubules in a proximal-to-distal direction, eventually extending the entire length of the midpiece and principal piece but not reaching their full diameter until step 16. At step 9, the nucleus begins to elongate and condense. Also at this step, the annulus—a septin-based ring of dense material—starts to form and surrounds the axoneme at its base (Guan et al., 2009). At step 15, the annulus migrates distally along the axoneme to the future site of the midpiece/principal piece junction (Guan et al., 2009; Kwitny et al., 2010). The axoneme and outer dense fibers proximal to this site are now surrounded by the spermatid’s caudal cytoplasm and will become the midpiece. Beginning at step 15, mitochondria in the developing midpiece migrate to the axoneme and condense around the axoneme and outer dense fibers (Russell et al., 1990). In step 16, the flagellar membrane becomes closely opposed to the mitochondrial sheath in the midpiece and the excess cytoplasm is eliminated as the residual body (O’Donnell et al., 2011). Mature sperm are then released into the lumen and exit the testis.


Intraflagellar transport is essential for mammalian spermiogenesis but is absent in mature sperm.

San Agustin JT, Pazour GJ, Witman GB - Mol. Biol. Cell (2015)

Key steps in the development of the mouse sperm flagellum during spermiogenesis. Adapted from Russell et al. (1990). Boxed events were determined from our experiments unless stated otherwise. Steps 1–8 are round spermatids, before the beginning of nuclear condensation and elongation in step 9. Based on the rat (Leblond and Clermont, 1952; Russell et al., 1990), the axoneme is assembled to full length in step 2-3. Assembly of outer dense fibers (ODFs) around the axoneme begins at the proximal end of the midpiece of step 8 spermatids; the process is completed just before the mature sperm is released into the lumen of the seminiferous tubule. Fibrous sheath (FS) assembly begins at the distal end of the principal piece of step 2 rat spermatids with the formation of fibrous sheath columns along the axonemal doublet microtubules 3 and 8; a similar event is presumed to take place in step 2-3 mouse spermatids. Assembly of fibrous sheath ribs on the columns starts in step 10 spermatids and is complete in step 13 spermatids. The manchette is first seen in step 8 spermatids and disappears by step 14. The annulus slides distally down the axoneme to its final location between the distal end of the midpiece and the proximal end of the principal piece when step 15 is reached (Kwitny et al., 2010). The mitochondria then condense along the length of the midpiece.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4666132&req=5

Figure 2: Key steps in the development of the mouse sperm flagellum during spermiogenesis. Adapted from Russell et al. (1990). Boxed events were determined from our experiments unless stated otherwise. Steps 1–8 are round spermatids, before the beginning of nuclear condensation and elongation in step 9. Based on the rat (Leblond and Clermont, 1952; Russell et al., 1990), the axoneme is assembled to full length in step 2-3. Assembly of outer dense fibers (ODFs) around the axoneme begins at the proximal end of the midpiece of step 8 spermatids; the process is completed just before the mature sperm is released into the lumen of the seminiferous tubule. Fibrous sheath (FS) assembly begins at the distal end of the principal piece of step 2 rat spermatids with the formation of fibrous sheath columns along the axonemal doublet microtubules 3 and 8; a similar event is presumed to take place in step 2-3 mouse spermatids. Assembly of fibrous sheath ribs on the columns starts in step 10 spermatids and is complete in step 13 spermatids. The manchette is first seen in step 8 spermatids and disappears by step 14. The annulus slides distally down the axoneme to its final location between the distal end of the midpiece and the proximal end of the principal piece when step 15 is reached (Kwitny et al., 2010). The mitochondria then condense along the length of the midpiece.
Mentions: Previously spermatogenesis was carefully examined in the rat (Leblond and Clermont, 1952; Russell et al., 1990). Although mouse spermatogenesis has not been so thoroughly characterized, Russell et al. (1990) built on the existing literature for both rat and mouse to provide a very useful description of the events during mouse spermiogenesis. To assist in interpreting the effects of the Ift88 mutation on sperm development, we have combined the diagrams of Russell et al. (1990) with our observations to order the key steps of flagellar development during mouse spermiogenesis (Figure 2). Spermatogenesis, or the development of sperm, begins with germ cells dividing and undergoing meiosis to generate spermatids. These develop into spermatozoa through the process of spermiogenesis. Spermiogenesis can be divided into 16 steps (Arabic numerals in Figure 2), which occur in synchronous waves along the seminiferous tubules of the testes. A section through a tubule will reveal germ cells at three or four stages of spermatogenesis, with one or two of these being spermiogenic. The more mature cells are organized in a band near the central lumen, and progressively less mature cells are localized in zones progressively closer to the outer surface or boundary of the tubule. Twelve distinct morphologies of the tubule (called stages and written in Roman numerals) can be distinguished by the steps of development occurring in a given tubule cross-section. For example, a section through a stage IV tubule will reveal step 15 spermatids with their flagella extending into the lumen of the tubule and step 4 spermatids located in a band between the lumen and the outer surface of the tubule. Spermiogenesis begins at step 1 with the appearance of haploid, round spermatids arising from two sequential meiotic divisions of the diplotene spermatocytes. During step 2-3, the 9 + 2 flagellar axoneme begins to elongate from a basal body located just below the plasma membrane and reaches nearly full length (Irons and Clermont, 1982). At this time, the axoneme is tightly surrounded by the flagellar membrane, which is continuous with cellular plasma membrane. Also during step 2-3, the precursors or “anlagen” of the fibrous sheath columns begin to form at the distal end of the flagellum (Sakai et al., 1986). The fibrous sheath columns and ribs subsequently are assembled in a distal-to-proximal direction in what will become the principal piece of the sperm (Irons and Clermont, 1982). Between steps 6 and 7 (Russell et al., 1990), the basal body with attached axoneme migrates inward to the nucleus and pulls the plasma membrane along with it to create an invagination of the plasma membrane that now surrounds the proximal portion of the flagellum. At step 8, the outer dense fibers begin to form at the proximal end of the axoneme. The fibers assemble along the axonemal doublet microtubules in a proximal-to-distal direction, eventually extending the entire length of the midpiece and principal piece but not reaching their full diameter until step 16. At step 9, the nucleus begins to elongate and condense. Also at this step, the annulus—a septin-based ring of dense material—starts to form and surrounds the axoneme at its base (Guan et al., 2009). At step 15, the annulus migrates distally along the axoneme to the future site of the midpiece/principal piece junction (Guan et al., 2009; Kwitny et al., 2010). The axoneme and outer dense fibers proximal to this site are now surrounded by the spermatid’s caudal cytoplasm and will become the midpiece. Beginning at step 15, mitochondria in the developing midpiece migrate to the axoneme and condense around the axoneme and outer dense fibers (Russell et al., 1990). In step 16, the flagellar membrane becomes closely opposed to the mitochondrial sheath in the midpiece and the excess cytoplasm is eliminated as the residual body (O’Donnell et al., 2011). Mature sperm are then released into the lumen and exit the testis.

Bottom Line: This mutation is highly disruptive to ciliary assembly in other organs.Ift88(-/-) mice are completely sterile.The short flagella rarely have axonemes but assemble ectopic microtubules and outer dense fibers and accumulate improperly assembled fibrous sheath proteins.

View Article: PubMed Central - PubMed

Affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.

No MeSH data available.


Related in: MedlinePlus