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Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli.

D'Alterio C, Tran DD, Yeung MW, Hwang MS, Li MA, Arana CJ, Mulligan VK, Kubesh M, Sharma P, Chase M, Tepass U, Godt D - J. Cell Biol. (2005)

Bottom Line: Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length.Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length.This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Toronto, Toronto, Ontario, Canada, M5S 3G5.

ABSTRACT
Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

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Expression of Cad99C during oogenesis. (A–F) Distribution of Cad99C mRNA in egg chambers at different stages of oogenesis. Arrows point to centripetal follicle cells in C, micropyle-forming follicle cells in E, and dorsal appendages in F. (G and H) Cad99C protein (red) is found on the apical surface of follicle cells (Fc) and from stage 6 onward is only seen in follicle cells that contact the oocyte (Oc). Armadillo (Arm; green) labels the membranes of germline and follicle cells. Numbers indicate stages of oogenesis. Bars, 100 μm.
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fig1: Expression of Cad99C during oogenesis. (A–F) Distribution of Cad99C mRNA in egg chambers at different stages of oogenesis. Arrows point to centripetal follicle cells in C, micropyle-forming follicle cells in E, and dorsal appendages in F. (G and H) Cad99C protein (red) is found on the apical surface of follicle cells (Fc) and from stage 6 onward is only seen in follicle cells that contact the oocyte (Oc). Armadillo (Arm; green) labels the membranes of germline and follicle cells. Numbers indicate stages of oogenesis. Bars, 100 μm.

Mentions: To identify novel regulators of cell and tissue morphogenesis, we studied the expression patterns of uncharacterized members of the cadherin gene superfamily (for review see Tepass et al., 2000; Hill et al., 2001) during D. melanogaster oogenesis, when follicle cells undergo a series of well-described morphogenetic movements (for review see Horne-Badovinac and Bilder, 2005). Cad99C, a cadherin gene that we named after its chromosomal map position, is transcribed in cells of the follicular epithelium, but not in the germline cyst (Fig. 1, A–F). Changes in the Cad99C expression level largely coincide with morphogenetically active phases of follicle cells. Cad99C mRNA was found in anterior and posterior follicle cells at stages 2–5 but was restricted to posterior follicle cells at late stage 6. Follicle cells that move over the oocyte at stage 9 and form a columnar epithelium at stage 10a expressed very high levels of Cad99C transcript. By stage 10b, high levels of expression were retained only in centripetal follicle cells that migrate inward to envelope the oocyte anteriorly. Expression levels peaked again in all follicle cells when they flattened to accommodate the growth of the oocyte. During late oogenesis, some follicle cells form tubelike structures—the micropyle and dorsal appendages—which is a process accompanied by a local increase of Cad99C expression. This dynamic expression profile suggested that Cad99C makes important contributions to follicle cell development. Consistent with its mRNA distribution, Cad99C protein (Fig. 1, G and H) was first seen during stages 2–5 of oogenesis in anterior and posterior terminal follicle cells. Beginning with stage 6, Cad99C was only detected in follicle cells that are in contact with the oocyte, a distribution that persists for the rest of oogenesis. At all stages, Cad99C was located on the apical plasma membrane of follicle cells, which faces the oocyte.


Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli.

D'Alterio C, Tran DD, Yeung MW, Hwang MS, Li MA, Arana CJ, Mulligan VK, Kubesh M, Sharma P, Chase M, Tepass U, Godt D - J. Cell Biol. (2005)

Expression of Cad99C during oogenesis. (A–F) Distribution of Cad99C mRNA in egg chambers at different stages of oogenesis. Arrows point to centripetal follicle cells in C, micropyle-forming follicle cells in E, and dorsal appendages in F. (G and H) Cad99C protein (red) is found on the apical surface of follicle cells (Fc) and from stage 6 onward is only seen in follicle cells that contact the oocyte (Oc). Armadillo (Arm; green) labels the membranes of germline and follicle cells. Numbers indicate stages of oogenesis. Bars, 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2171266&req=5

fig1: Expression of Cad99C during oogenesis. (A–F) Distribution of Cad99C mRNA in egg chambers at different stages of oogenesis. Arrows point to centripetal follicle cells in C, micropyle-forming follicle cells in E, and dorsal appendages in F. (G and H) Cad99C protein (red) is found on the apical surface of follicle cells (Fc) and from stage 6 onward is only seen in follicle cells that contact the oocyte (Oc). Armadillo (Arm; green) labels the membranes of germline and follicle cells. Numbers indicate stages of oogenesis. Bars, 100 μm.
Mentions: To identify novel regulators of cell and tissue morphogenesis, we studied the expression patterns of uncharacterized members of the cadherin gene superfamily (for review see Tepass et al., 2000; Hill et al., 2001) during D. melanogaster oogenesis, when follicle cells undergo a series of well-described morphogenetic movements (for review see Horne-Badovinac and Bilder, 2005). Cad99C, a cadherin gene that we named after its chromosomal map position, is transcribed in cells of the follicular epithelium, but not in the germline cyst (Fig. 1, A–F). Changes in the Cad99C expression level largely coincide with morphogenetically active phases of follicle cells. Cad99C mRNA was found in anterior and posterior follicle cells at stages 2–5 but was restricted to posterior follicle cells at late stage 6. Follicle cells that move over the oocyte at stage 9 and form a columnar epithelium at stage 10a expressed very high levels of Cad99C transcript. By stage 10b, high levels of expression were retained only in centripetal follicle cells that migrate inward to envelope the oocyte anteriorly. Expression levels peaked again in all follicle cells when they flattened to accommodate the growth of the oocyte. During late oogenesis, some follicle cells form tubelike structures—the micropyle and dorsal appendages—which is a process accompanied by a local increase of Cad99C expression. This dynamic expression profile suggested that Cad99C makes important contributions to follicle cell development. Consistent with its mRNA distribution, Cad99C protein (Fig. 1, G and H) was first seen during stages 2–5 of oogenesis in anterior and posterior terminal follicle cells. Beginning with stage 6, Cad99C was only detected in follicle cells that are in contact with the oocyte, a distribution that persists for the rest of oogenesis. At all stages, Cad99C was located on the apical plasma membrane of follicle cells, which faces the oocyte.

Bottom Line: Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length.Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length.This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Toronto, Toronto, Ontario, Canada, M5S 3G5.

ABSTRACT
Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

Show MeSH
Related in: MedlinePlus