Projects
Urogenital/reproductive organ formation is one of the most important and attractive organogenesis plan for mammalian. The system is necessary for reproductive functions in various aspects, such as for copulation, ovulation, ejaculation, implantation and delivery. The male and female reproductive/urogenital organs show a tremendous degree of structural and functional diversity between the sexes. Various growth factors and transcription factors constitute molecular genetic cascades for the development of these structures.
Our laboratory is analyzing the molecular genetic cascade for such urogenital/reproductive organ formation.
We have been working on the role of several growth factor system during urogenital/reproductive organ formation. (Haraguchi et.al., Development 127:
2471-2479,2000, Haraguchi et.al.,Development 128:4241-4250,2001, Suzuki et.al.,Development 131:6209-6220,2003, Haraguchi et.al.,Development 134:525-533,2007, Ohta et al.,Development 24:4315-24,2007, Nishida et al, Endocrinology 149:2090-7,2008, Suzuki et.al., Development 136:367-372,2009.etc etc ).
For several decades, researchers have tackled to analyze the developmental programs for organogenesis. Significant progresses have obtained for organogenetis plant, such as for limb, body, head formation. However, our understanding for urogenital/reproductive organ formation remains virtually very poor. We are analyzing molecular genetic cascade utilizing conditional mouse models to tackle the next series of project.
Our lab is an international lab holding many international students ( basic lab semi is done in English ( students secret talks are also in English....)).
We are proud to comment some our previous colleagues became PIs after getting back home countries.
Lets join gen yamada lab kumamoto Univ (working on Urogenital/reproductive organ formation)
Please also see our PDFs at repository site and search by Yamada,Gen
http://reposit.lib.kumamoto-u.ac.jp/?lang=en
Our lab mail
transg(place @)kumamoto-u.ac.jp
Several on-going projects;
1. Analysis of urogenital/reproductive organ formation; molecular mechanisms of limb and external genitalia formation-its similarity and divergence.
2. Coordination of organogenesis; growth factor cascades necessary for coordinated development of urogenital/reproductive organ formation at caudal embryos.
3. Analysis of epithelial development in several organs; the uniqueness of epithelial differentiation program in urogenital/reproductive tissues as compared with other organs, such as for skin. How reproductive tissues achieve unique nature of epithelial development ? Suzuki et.al., Development 136:367-372,2009.
"Similar" developmental plans; a prologue music.......
It is intriguing and important to note the potential similarities and also divergences of some “shared” devel- opmental plans between “general” organogenesis and reproductive/urogenital organ formation. Figure shows an example of the initial process of reproductive organ development in comparison with that of limb ( arms, legs...) appendages as an example somatic organ development .
Epithelial-mesenchymal interactions play an essen- tial role in regulating a wide variety of developmental processes. Signaling between the epithelium and the mesenchyme governs many aspects of organo- genesis, from the initiation of organ development to dif- ferentiation.
The external genital anlage is the genital tubercle (GT). Pioneering studies have suggested that GT development may have some similarities to limb append- age development, with both structures exhibiting organ outgrowth. We found several landmarking observations that both appendages express "similar" signal genes in the distal epithelia. We gave a name DUE in the case of GT for such epithelia (Fig)
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Developmental "coordination"; too huge and fundamental problem to tackle.....
We have interests on the coordinated developmental programs for urogenital/reproductive organ formation. " Coordination" is sort of common sense in development but virtually no molecular genetic studies have been tried to prove such basic processes at tissue levels.
It has been suggested that the cloaca/urogenital sinus and adjacent tissues differentiate into the urogenital and reproductive organs, including the urinary bladder in both sexes. This is supported by reports on complex congenital malformations such as: exstrophy-epispadias complex (exstrophy of cloaca or bladder and abnormal dorsal external genitalia); defective body wall, bladder and genitalia formation; and limb body wall defects that are probably caused by abnormalities in early development of the cloaca and urogenital sinus. The constellation of defects reported in affected individuals suggests that coordinated developmental programs regulate bladder and external genital morphogenesis. However, the signaling and structural contributions of the transient embryonic cloaca to formation of multiple urogenital and reproductive organs inside and outside the pelvic cavity remain mystery.
By genetically labeling hedgehog-responding tissue lineages adjacent to the cloaca and urogenital sinus, we defined the contribution of these tissues to the bladder and external genitalia. We discovered that development of smooth muscle myosin-positive embryonic bladder mesenchyme requires Shh signaling, and that the bladder mesenchyme and dorsal (upper) external genitalia derive from Shh-responsive peri-cloacal mesenchyme. Thus, the mesenchymal precursors for multiple urogenital structures derive from peri-cloacal mesenchyme and the coordination of urogenital organ formation from these precursors is orchestrated by Shh signals. This is just the beginning and many works are necessary to analyze the mode of coordination in organogenesis.
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