华人科学家发现生育缺陷基因

　　

生物通报道：来自南加州大学（University of Southern California，USC）的华人科学家柴杨（Yang Chai，音译）利用一种动物模式揭示了导致先天性头骨畸形的遗传分子生物学原因，以及如何阻止这种情况的发生。这一研究结果公布在Development杂志上。

这位早年毕业于北京大学口腔学院，现任南加州大学颅面研究与治疗部（craniofacial sciences and therapeutics in the USC School of Dentistry）主任的科学家带领其它科研人员将导致头骨前额部分（the forehead and frontal part of the skull）畸形的遗传因素定位在了一种称之为转化生长因子β（transforming growth factor-beta，TGF-β）基因上。

TGF-β属于一组新近发现的调节细胞生长和分化的TGF-β超家族。之所以称为转化生长因子，是因为这种细胞因子能使正常的成纤维细胞的表型发生转化，即在表皮生长因子（EGF）同时存在的条件下，改变成纤维细胞巾壁生长特性而获得在琼脂中生长的能力，并失去生长中密度信赖的抑制作用。这一家族除TGF-β外，还有活化素（activins）、抑制素（inhibins）、缪勒氏管抑制质（Mullerian inhibitor substance,MIS）和骨形成蛋白（bone morpho-genetic proteins,BMPs），并且与早先报道的从非洲绿猴肾上皮细胞BSC-1所分泌的生长抑制因子是同一物。

为了研究清楚这一基因的作用，研究人员采用了一种特殊的实验手段，即只敲除了小鼠胚胎用以构建面骨和软骨的头盖骨神经脊细胞（cranial neural crest cells）中的TGF-β基因，这主要是因为如果敲除了体内每一个单细胞中的TGF-β基因，这个胚胎就会过早死亡，这样研究人员就无法跟踪分析头盖骨发育过程中TGF-β基因所起的作用。通过这一系列的实验，研究人员最终确定了TGF-β在前额骨正常发育过程中的重要作用。（生物通记者：张迪）

附：
柴杨（Yang Chai）

教育经历：

INSTITUTION AND LOCATION	DEGREE	YEAR(s)	FIELD OF STUDY
University of Southern California,  Los Angeles, California	D.D.S.	1994-1996	Dentistry
University of Southern California,  Los Angeles, California	Postdoctoral	1991-1994	Craniofacial Molecular Biology
University of Southern California,  Los Angeles, California	Ph.D.	1987-1991	Craniofacial Biology
School of Stomatology,  Peking University, Beijing, China	Residency	1984-1986	Oral-Maxillofacial Surgery
School of Stomatology,  Peking University, Beijing, China	D.M.D. (MB)	1979-1984	Stomato

主要论著：
Sasaki T, Ito Y, Bringas Jr. P, Chou S, Urata M, Slavkin HC, Chai Y. (2005).  TGF-beta-mediated FGF signaling is critical for regulating cranial neural crest cell proliferation during frontal bone development. Development 133, 371-381

Choudhary B, Ito Y, Makita T, Sasaki T, Chai Y, Sucov HM. (2005).  Cardiovascular malformations with normal smooth muscle differentiation in neural crest-specific type II TGFbeta receptor (Tgfbr2) mutant mice. Dev Biol. (In Press)

Ishii M, Han J, Yen HY, Sucov HM, Chai Y, Maxson RE Jr. (2005).  Combined deficiencies of Msx1 and Msx2 cause impaired patterning and survival of the cranial neural crest. Development. 132(22):4937-50.

Hosokawa R, Urata MM, Ito Y, Bringas P Jr., Chai Y. (2005). Functional significance of Smad2 in regulating basal keratinocyte migration during wound healing. J Inves Dermatol. 125: 1302-1309

Zhao H, Bringas P Jr, Chai Y. (2005).  An in vitro model for characterizing the post-migratory cranial neural crest cells of the first branchial arch. Dev Dyn. [Epub ahead of print]

Plikus MV, Zeichner-David M, Mayer JA, Reyna J, Bringas P, Thewissen JGM, Snead ML, Chai Y, Chuong CM. (2005). Morphoregulation of teeth: modulating the number, size, shape and differentiation by tuning Bmp activity. Evolution & Development 7:5, 440 –457

Jamora C, Lee P, Kocieniewski P, Azhar M, Hosokawa R, Chai Y, Fuchs E. (2005). A Signaling Pathway Involving TGF-beta2 and Snail in Hair Follicle Morphogenesis. PLoS Biol. 3(1):e11

Cui XM, Shiomi N, Chen J, Saito T, Yamamoto T, Ito Y, Bringas Jr. P, Chai Y, Shuler CF. (2005) Overexpression of Smad2 in TGF-beta3-null mutant mice rescues cleft palate.  Dev. Biol. 278, 193-202.

Sasaki T, Ito Y, Xu X, Han J, Bringas P Jr, Maeda T, Slavkin HC, Grosschedl R, Chai Y. (2005). LEF1 is a critical epithelial survival factor during tooth morphogenesis. Dev. Biol. 278,130-143.

Xu X, Bringas P Jr, Soriano P, Chai Y. (2005). PDGFR-alpha signaling is critical for tooth cusp and palate morphogenesis. Dev. Dyn. 232(1):75-84

Ito Y, Yeo JY, Chytil A, Han J, Bringas P Jr, Nakajima A, Shuler CF, Moses HL, Chai Y.  (2003). Conditional inactivation of TGF-beta IIR in cranial neural crest causes cleft palate and calvaria defects.  Development 130, 5269-5280.