Integrin beta-4 signaling plays a key role in mouse embryogenesis.
Integrins, by signaling between extracellular matrix and cell nucleus, serve critical roles in cell proliferation and survival. A knock-in mice was developed by a targeted deletion of the C-terminal segment of the cytoplasmic tail of beta 4-integrin (beta 4-1355T). The beta 4-1355T mice had a longer gestational length, smaller litter sizes, lower fecundity rate, and higher frequency of early pregnancy loss. beta 4-1355T embryos demonstrated a high degree of fragmentation and asymmetry, with fewer surviving to either a morula or blastocyst stage. In wild-type oocytes and embryos, beta1, beta 4, and laminin-5 signals colocalized at the opposing surfaces of blastomeres and between the polar bodies and oocytes. Blastomeres within the beta 4-1355T embryos were less cohesive, with a more diffuse expression of beta 4 and laminin-5 compared with wild type. The alpha 6 beta 4_laminin-5 interaction appears to be vital for maintaining the cohesiveness between the cells of the embryo. Deciphering the role of integrins such as beta 4 in embryogenesis may help explain in vitro fertilization failures.
Roberts
Jeffrey E
JE
Pacific Centre for Reproductive Medicine, Burnaby, British Columbia, Canada.
Nikolopoulos
Sotiris N
SN
Oktem
Ozgur
O
Giancotti
Filippo
F
Oktay
Kutluk
K
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D002970:Cleavage Stage, Ovum / Q000378:metabolism; D046149:Embryo Culture Techniques; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D005298:Fertility; D005307:Fertilization in Vitro; D055879:Gene Knock-In Techniques; D006801:Humans; D039663:Integrin beta4 / Q000235:genetics / Q000378:metabolism*; D008098:Litter Size; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D054315:Oocyte Retrieval; D010062:Ovulation Induction; D011247:Pregnancy; D012098:Reproduction / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
D039663:Integrin beta4