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Localized rbp4 expression in the yolk syncytial layer plays a role in yolk cell extension and early liver development.

Li Z, Korzh V, Gong Z - BMC Dev. Biol. (2007)

Bottom Line: Knockdown of Rbp4 in the YSL resulted in shortened yolk extension as well as the formation of two liver buds, which could be due to impaired migration of liver progenitor cells. rbp4 appears also to regulate the extracellular matrix protein Fibronectin1 (Fn1) specifically in the ventro-lateral yolk, indicating a role of Fn1 in liver progenitor migration.The characteristic expression pattern of rbp4 suggests that the YSL is patterned despite its syncytial nature.YSL-expressed Rbp4 plays a role in formation of both yolk extension and liver bud, the latter may also require migration of liver progenitor cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, National University of Singapore, Singapore. g0203805@nus.edu.sg

ABSTRACT

Background: The number of genes characterized in liver development is steadily increasing, but the origin of liver precursor cells and the molecular control of liver formation remain poorly understood. Existing theories about formation of zebrafish visceral organs emphasize either their budding from the endodermal rod or formation of independent anlage followed by their later fusion, but none of these is completely satisfactory in explaining liver organogenesis in zebrafish.

Results: Expression of a gene encoding the retinol binding protein 4 (Rbp4) was analyzed in zebrafish. rbp4, which is expressed mainly in the liver in adults, was shown to be expressed in the yolk syncytial layer (YSL) during early embryogenesis. At 12-16 hpf rbp4 expression was restricted to the ventro-lateral YSL and later expanded to cover the posterior YSL. We demonstrated that rbp4 expression was negatively regulated by Nodal and Hedgehog (Hh) signalling and positively controlled by retinoic acid (RA). Knockdown of Rbp4 in the YSL resulted in shortened yolk extension as well as the formation of two liver buds, which could be due to impaired migration of liver progenitor cells. rbp4 appears also to regulate the extracellular matrix protein Fibronectin1 (Fn1) specifically in the ventro-lateral yolk, indicating a role of Fn1 in liver progenitor migration. Since exocrine pancreas, endocrine pancreas, intestine and heart developed normally in Rbp4 morphants, we suggest that rbp4 expression in the YSL is required only for liver development.

Conclusion: The characteristic expression pattern of rbp4 suggests that the YSL is patterned despite its syncytial nature. YSL-expressed Rbp4 plays a role in formation of both yolk extension and liver bud, the latter may also require migration of liver progenitor cells.

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Analyses of rbp4 expression during late development and its regulation. (A-D) rbp4 expression in 24 hpf, 48 hpf, 4 dpf and 8 dpf wild-type embryos as indicated. A red arrow indicates the liver while a black arrow indicates the pericardium region. (E-H) rbp4 expression in cyc-/-, oep-/-, smu-/- and syu-/- embryos at 48 hpf as indicated. (I – L) rbp4 expression in various heterozygous and homozygous mib mutant embryos as indicated. Red arrows indicate the liver. Note precocious appearance of rbp4 expression in homozygous mutant liver at 48 hpf (J, L) compared to heterozygous mib embryos (I, K). (M, N) rbp4 expression in 48 hpf embryos treated with 10-6 M RA initiated from 12 hpf (M) or 18 hpf (N). (O, P) rbp4 expression in 48 hpf embryos treated with 10-5 M DEAB initiated from 12 hpf (O) and 18 hpf (P).
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Figure 2: Analyses of rbp4 expression during late development and its regulation. (A-D) rbp4 expression in 24 hpf, 48 hpf, 4 dpf and 8 dpf wild-type embryos as indicated. A red arrow indicates the liver while a black arrow indicates the pericardium region. (E-H) rbp4 expression in cyc-/-, oep-/-, smu-/- and syu-/- embryos at 48 hpf as indicated. (I – L) rbp4 expression in various heterozygous and homozygous mib mutant embryos as indicated. Red arrows indicate the liver. Note precocious appearance of rbp4 expression in homozygous mutant liver at 48 hpf (J, L) compared to heterozygous mib embryos (I, K). (M, N) rbp4 expression in 48 hpf embryos treated with 10-6 M RA initiated from 12 hpf (M) or 18 hpf (N). (O, P) rbp4 expression in 48 hpf embryos treated with 10-5 M DEAB initiated from 12 hpf (O) and 18 hpf (P).

Mentions: At 24 hpf, rbp4 expression in the YSL is restricted to its posterior part including that in the YCE (Figure 2A). This expression pattern remained unchanged at least until 48 hpf (Figure 2B). Later the expression spread anteriorly but remained excluded from the pericardium (Figure 2C). By 4 dpf, rbp4 expression was detected in the liver (Figure 2C). By 8 dpf the liver became the only tissue with detectable rbp4 expression (Figure 2D).


Localized rbp4 expression in the yolk syncytial layer plays a role in yolk cell extension and early liver development.

Li Z, Korzh V, Gong Z - BMC Dev. Biol. (2007)

Analyses of rbp4 expression during late development and its regulation. (A-D) rbp4 expression in 24 hpf, 48 hpf, 4 dpf and 8 dpf wild-type embryos as indicated. A red arrow indicates the liver while a black arrow indicates the pericardium region. (E-H) rbp4 expression in cyc-/-, oep-/-, smu-/- and syu-/- embryos at 48 hpf as indicated. (I – L) rbp4 expression in various heterozygous and homozygous mib mutant embryos as indicated. Red arrows indicate the liver. Note precocious appearance of rbp4 expression in homozygous mutant liver at 48 hpf (J, L) compared to heterozygous mib embryos (I, K). (M, N) rbp4 expression in 48 hpf embryos treated with 10-6 M RA initiated from 12 hpf (M) or 18 hpf (N). (O, P) rbp4 expression in 48 hpf embryos treated with 10-5 M DEAB initiated from 12 hpf (O) and 18 hpf (P).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2198918&req=5

Figure 2: Analyses of rbp4 expression during late development and its regulation. (A-D) rbp4 expression in 24 hpf, 48 hpf, 4 dpf and 8 dpf wild-type embryos as indicated. A red arrow indicates the liver while a black arrow indicates the pericardium region. (E-H) rbp4 expression in cyc-/-, oep-/-, smu-/- and syu-/- embryos at 48 hpf as indicated. (I – L) rbp4 expression in various heterozygous and homozygous mib mutant embryos as indicated. Red arrows indicate the liver. Note precocious appearance of rbp4 expression in homozygous mutant liver at 48 hpf (J, L) compared to heterozygous mib embryos (I, K). (M, N) rbp4 expression in 48 hpf embryos treated with 10-6 M RA initiated from 12 hpf (M) or 18 hpf (N). (O, P) rbp4 expression in 48 hpf embryos treated with 10-5 M DEAB initiated from 12 hpf (O) and 18 hpf (P).
Mentions: At 24 hpf, rbp4 expression in the YSL is restricted to its posterior part including that in the YCE (Figure 2A). This expression pattern remained unchanged at least until 48 hpf (Figure 2B). Later the expression spread anteriorly but remained excluded from the pericardium (Figure 2C). By 4 dpf, rbp4 expression was detected in the liver (Figure 2C). By 8 dpf the liver became the only tissue with detectable rbp4 expression (Figure 2D).

Bottom Line: Knockdown of Rbp4 in the YSL resulted in shortened yolk extension as well as the formation of two liver buds, which could be due to impaired migration of liver progenitor cells. rbp4 appears also to regulate the extracellular matrix protein Fibronectin1 (Fn1) specifically in the ventro-lateral yolk, indicating a role of Fn1 in liver progenitor migration.The characteristic expression pattern of rbp4 suggests that the YSL is patterned despite its syncytial nature.YSL-expressed Rbp4 plays a role in formation of both yolk extension and liver bud, the latter may also require migration of liver progenitor cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biological Sciences, National University of Singapore, Singapore. g0203805@nus.edu.sg

ABSTRACT

Background: The number of genes characterized in liver development is steadily increasing, but the origin of liver precursor cells and the molecular control of liver formation remain poorly understood. Existing theories about formation of zebrafish visceral organs emphasize either their budding from the endodermal rod or formation of independent anlage followed by their later fusion, but none of these is completely satisfactory in explaining liver organogenesis in zebrafish.

Results: Expression of a gene encoding the retinol binding protein 4 (Rbp4) was analyzed in zebrafish. rbp4, which is expressed mainly in the liver in adults, was shown to be expressed in the yolk syncytial layer (YSL) during early embryogenesis. At 12-16 hpf rbp4 expression was restricted to the ventro-lateral YSL and later expanded to cover the posterior YSL. We demonstrated that rbp4 expression was negatively regulated by Nodal and Hedgehog (Hh) signalling and positively controlled by retinoic acid (RA). Knockdown of Rbp4 in the YSL resulted in shortened yolk extension as well as the formation of two liver buds, which could be due to impaired migration of liver progenitor cells. rbp4 appears also to regulate the extracellular matrix protein Fibronectin1 (Fn1) specifically in the ventro-lateral yolk, indicating a role of Fn1 in liver progenitor migration. Since exocrine pancreas, endocrine pancreas, intestine and heart developed normally in Rbp4 morphants, we suggest that rbp4 expression in the YSL is required only for liver development.

Conclusion: The characteristic expression pattern of rbp4 suggests that the YSL is patterned despite its syncytial nature. YSL-expressed Rbp4 plays a role in formation of both yolk extension and liver bud, the latter may also require migration of liver progenitor cells.

Show MeSH