成形素是一类分泌性信号分子，它们在形成一定形状和尺寸的器官过程中起着关键作用。现在，辛辛那提儿童医院医学中心的研究人员已经知道这种分子在生物体中的工作方式，即扩散方式。这些新发现公布在10月15日的Cell上。
成形素在器官的形成中其重要作用，但是当这些分子发生功能故障时就可能造成器官缺陷和癌症。目前对成形素的工作方式有多种假说，其中包括细胞外扩散和转细胞理论（transcytosis）。细胞外扩散理论认为成形素在细胞表面移动；转细胞理论则认为细胞通过内吞作用转移成形素分子。成形素有很多种，在新的研究中，研究人员集中研究了TGF beta蛋白家族的工作方式。
儿童医院医学中心的林新华博士和同事在研究中用果蝇作为研究的模型，并且对果蝇的Dpp（Decapentaplegic）蛋白进行了研究。Dpp是一种与人类TGF beta蛋白结果相似的成形素分子。Dpp的作用是指导果蝇翅膀的形成。研究组证明Dpp成形素分子主要分布在细胞表面，这意味着Dpp成形素通过细胞外扩散机制来运动。
研究人员还用抑制内吞作用并检测Dpp成形素的运动的方法对这种推测进行了验证。他们发现抑制内吞作用干扰了细胞转换Dpp信号的能力，但是却不会阻碍Dpp横跨细胞的运动。这个实验也揭示出了内吞作用在Dpp传递信号活动中的作用。
这项研究使我们进一步了解了器官形成的机制，并且还可能促进器官缺陷和癌症的治疗。这些对成形素作用机制的新了解将会促进对相关疾病的新治疗药物的研发。
有关这个基因的详细功能描述：
decapentaplegic
Function
decapentaplegic is responsible for dorsal/ventral polarity in the fly. In a second phase of its activity, as segments appear, dpp functions in the definition of boundaries between segmental compartments. As part of this process, dpp, along with wingless and hedgehog, defines the position of future limbs, including wings, legs and antenna. dpp also has an independent role in the structuring of the mesoderm. Later, during the final process of appendage development, and acting downstream of engrailed and hedgehog, dpp defines boundaries between appendage compartments assuring correct anterior/posterior polarity. dpp has an analogous function in the development of the eye, where it is primarily responsible for the progression of the morphogenetic furrow, the induction site of the Drosophila retina.
The effects on the dorsal-most region of the fly are regulated by Saxophone in conjuction with Thick veins and Punt. Without DPP signals through Saxophone, the amnioserosa, the most dorsal ectodermal tissue, does not develop properly and dorsal closure, the sealing of a dorsal "hole" in the developing embryo does not take place. The dorsal region is ventralized, and it develops characteristics of the ventral neuroectoderm.
The initial effects of DPP on the heart and on visceral mesoderm (gut muscles) are mediated by Thick veins and Punt. An early and important event in the subdivision of the mesoderm is the restriction of tinman expression to dorsal mesodermal cells, the precursors of heart cells.
DPP also induces local differentiation in the endoderm (Manak J. R., 1995). The actions of dpp on gene activation are not always positive. dpp actively suppresses the development of the proventriculus, confining it to the foregut.
Secreted in an anterior to posterior stripe in the trunk, DPP intersects wingless expressing cells under the control of hedgehog in segmentally repeated dorsal/ventral stripes. All three proteins are needed to allocate cells for the formation of imaginal discs, which will ultimately develop into appendages. This process involves induction of distal-less and aristaless, both of which are needed to specify the tips of appendages (Campbell G., 1993 and Diaz-Benjumea F. J., 1994).
Protein
The carboxy-terminal 100 amino acids have 25-40% homology to human and porcine TGFbeta, Inhibin A and Inhibin B. The homologous region is preceeded by three arginine dimers that each function as proleolytic cleavage sites (Padget R. W., 1987).
Subcellular location
Secreted
--------------------------------------------------------------------------------
Expression Patterns
Early dpp expression pattern in the ectoderm is dynamic, consisting of three phases. Phase I, in which dpp is expressed in a broad dorsal domain, depends on elements in the dpp second intron that interact with the Dorsal transcription factor to repress transcription ventrally. In contrast, in phases II and III, dpp is expressed first in broad longitudinal stripes (phase II) and subsequently in narrow longitudinal stripes (phase III) (Schwyter D. H., 1995). dpp is also expressed in the visceral mesodermal midgut, where it regulates formation of caeca. DPP has a major role in compartment formation between visceral segments and is expressed there during the process of segmentation (Manek J. R., 1994).
dpp and Ubx proteins are expressed in overlapping domains in the visceral mesoderm in parasegment 7. The dpp domain extends further anteriorly by half a parasegment. (Reuter R., 1990)
dpp expression in the gut, at least some of which is presumably endodermal, includes the presumptive pharynx, a portion of the presumptive exophagus, the primordia of the gastric caeca, the parasegment 7 region of the midgut, and a portion of the presumptive hindgut. As these expression patterns are generated from promoter fragments, the finding of DPP expression in the endoderm should remain controvertial until confirmed (Jackson P. D., 1994).
dpp protein is present in the visceral mesoderm at and anterior to the second midgut constriction from embryonic stage 14. By stage 16, dpp protein surrounds the adjacent endoderm cells. (Panganiban G., 1990)
Development of the Drosophila retina occurs asynchronously. The leading edge of differentiation, its front marked by the morphogenetic furrow, progresses across the eye disc epithelium over a 2 day period. The mechanism by which this front advances suggest that developing retinal cells behind the furrow drive the progression of morphogenesis utilizing the products of the hedgehog and decapentaplegic genes. Analysis of hh and dpp genetic mosaics indicates that the products of these genes act as diffusible signals in this process. Expression of dpp in the morphogenetic furrow is closely correlated with the progression of the furrow under a variety of conditions. HH, synthesized by differentiating cells, induces the expression of dpp, which appears to be a primary mediator of furrow movement (Heberlein U., 1993).
dpp is expressed during oogenesis in anterior follicle cells. Expression is first detectable at the end of stage 8 in approximately 20 to 30 somatic follicle cells at the anterior tip of the egg chamber. (Twombly V., 1996).
--------------------------------------------------------------------------------
Sequences
GenBank
--------------------------------------------------------------------------------
Regulatory Regions
Manak, J. R., Mathies, L. D. and Scott, M. P. Regulation of a decapentaplegic midgut enhancer by homeotic proteins. Development 120, 3605-3619 (1994):
DMDPPME D.melanogaster dpp midgut enhancer DNA. : regulation by homeotic proteins
Regulatory element Localisation of element Trans-regulatory factor (TRANSFAC links) Reference
negative regulatory element 5'-flanking region ENGRAILED Sanicola et al., 1995
--------------------------------------------------------------------------------
Regulatory Connections
--------------------------------------------------------------------------------
Protein & Transcript Data
FlyBase
--------------------------------------------------------------------------------
Links
FlyBase ID: FBgn0000490
For detailed review about this gene see THE INTERACTIVE FLY Data Base.
相关研究：
Nuclear interpretation of Dpp signaling in Drosophila.
Eyeing hedgehog and decapentaplegic [PDF文件]
The Drosophila decapentaplegic and short gastrulation genes ...[PDF文件]
JNK and decapentaplegic signaling control adhesiveness [PDF文件]
Dynamics of decapentaplegic expression during regeneration of the ...[PDF文件]
miRNA: mir-26a Human predicted target[PDF文件]
TGF- Signaling: The Known and the Unknown[PDF文件]
Roles of the JNK signaling pathway in Drosophila morphogenesis [PDF文件]
Bone morphogenetic proteins: basic concepts[PDF文件]
TGF ß Signal Transduction in Endothelial Cells[PDF文件]
Limb morphogenesis: connections between patterning and growth[PDF文件]
