The mouse forkhead gene Foxc1 is required for primordial germ cell migration and antral follicle development.
Foxc1 encodes a forkhead/winged helix transcription factor expressed in many embryonic tissues. Previous studies have investigated defects in the urogenital system of Foxc1 null mutants, but the mechanisms underlying the abnormal development of the gonad have not been explored. From earliest stages, the mutant ovaries are smaller than normal, with fewer germ cells and disorganized somatic issue. No bursa membrane is formed, and the oviduct remains uncoiled. Although germ cells are specified correctly, many of them do not migrate to the gonadal ridge, remaining trapped in the hindgut. Consequently, the number initially reaching the gonad is less than 25% of normal. Once in the ovary, germ cells proliferate normally, but the supporting somatic cells are not organized correctly. Since mutant embryos die at birth, further development was followed in ovaries grafted underneath the kidney capsule of ovariectomized females. Transplanted ovaries display normal folliculogenesis up to preantral stages. However, no follicles develop beyond early antral stages. Mutant follicles are often polyovulatory and have disrupted theca and granulosa cell layers. We conclude that alongside its previously known roles in kidney, cardiovascular and eye development, Foxc1 has essential functions during at least two stages of gonad development-germ cell migration and folliculogenesis.
Mattiske
Deidre
D
Department of Cell Biology, Duke University Medical Center, Box 3709, Durham, NC 27710, USA.
Kume
Tsutomu
T
Hogan
Brigid L M
BL
D000818:Animals; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism / Q000502:physiology*; D005697:Galactosides / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006579:Heterozygote; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007211:Indoles / Q000378:metabolism; D007668:Kidney / Q000196:embryology; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D009154:Mutation; D006080:Ovarian Follicle / Q000196:embryology* / Q000378:metabolism; D010053:Ovary / Q000378:metabolism / Q000637:transplantation; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013799:Theca Cells / Q000378:metabolism; D013997:Time Factors
D051858:Forkhead Transcription Factors; C112890:Foxc1 protein, mouse; D005697:Galactosides; D007211:Indoles; D049452:Green Fluorescent Proteins; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside