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Title :Regulation of outgrowth and apoptosis for the terminal appendage: external genitalia: development by concerted actions of BMP signaling
Authors :Suzuki, Kentaro
Bachiller, Daniel
YiPing, P. Chen
Kamikawa, Mami
Ogi, Hidenao
Haraguchi, Ryouma
Ogino, Yukiko
Minami, Yasuhiro
Mishina, Yuji
Ahn, Kyung
Crenshaw III, E.Bryan
Yamada, Gen
Issue Date :Dec-2003
Citation jtitle :Development
vol. :130
no. :25
start page :6209
end page :6220
Abstract :Extra-corporal fertilization depends on the formation of copulatory organs: the external genitalia. Coordinated growth and differentiation of the genital tubercle (GT), an embryonic anlage of external genitalia, generates a proximodistally elongated structure suitable for copulation, erection, uresis and ejaculation. Despite recent progress in molecular embryology, few attempts have been made to elucidate the molecular developmental processes of external genitalia formation. Bone morphogenetic protein genes (Bmp genes) and their antagonists were spatiotemporally expressed during GT development. Exogenously applied BMP increased apoptosis of GT and inhibited its outgrowth. It has been shown that the distal urethral epithelium (DUE), distal epithelia marked by the Fgf8 expression, may control the initial GT outgrowth. Exogenously applied BMP4 downregulated the expression of Fgf8 and Wnt5a, concomitant with increased apoptosis and decreased cell proliferation of the GT mesenchyme. Furthermore, noggin mutants and Bmpr1a conditional mutant mice displayed hypoplasia and hyperplasia of the external genitalia respectively. noggin mutant mice exhibited downregulation of Wnt5a and Fgf8 expression with decreased cell proliferation. Consistent with such findings, Wnt5a mutant mice displayed GT agenesis with decreased cell proliferation. By contrast, Bmpr1a mutant mice displayed decreased apoptosis and augmented Fgf8 expression in the DUE associated with GT hyperplasia. These results suggest that some of the Bmp genes could negatively affect proximodistally oriented outgrowth of GT with regulatory functions on cell proliferation and apoptosis. The DUE region can be marked only until 14.0 dpc (days post coitum) in mouse development, while GT outgrowth continues thereafter. Possible signaling crosstalk among the whole distal GT regions were also investigated.
URL :http://dev.biologists.org/cgi/content/full/130/25/6209
Type Local :雑誌掲載論文
Publisher :Company of Biologists
URI :http://hdl.handle.net/2298/10389
Appears in Collections:Journal Article( Institute of Resource Development and Genetics)
Please use this identifier to cite or link to this item: http://hdl.handle.net/2298/10389