Sonic hedgehog, a morphogen in penile development

描述(由申请人提供)：建议的研究将审查 Sonic Hedgehog(Shh)在阴茎发育中的作用及其调节失调 糖尿病引起的勃起功能障碍的这一途径。嘘是个秘密的人 在间充质-上皮相互作用中起关键作用的糖肽 在组织发育过程中。我们将展示初步证据表明Shh发出信号 该语体在阴茎发育过程中受到神经调节，在成人中， 并建议确定糖尿病神经病变对其表达的影响 和躯体中Shh的活性。糖尿病是一种常见的风险 勃起功能障碍的因素，这是一种毁灭性的病理发展 这影响了1,000-3,000万美国男性，并使 仅住院泌尿外科护理(1985美元)。虽然血管病变和 神经病变是糖尿病自然病程中常见的并发症，准确地说 糖尿病阳萎的原因尚不清楚。我们将检验这一假设 神经Shh信号在建立和维持正常状态中是基本的 糖尿病患者阴茎形态与勃起功能障碍 神经病是由Shh的内稳态功能紊乱引起的 路径。这项提议的力量在于它有可能提供新颖和 对糖尿病导致勃起机制的重要洞察 功能。这可能为预防或治疗的新疗法提供依据。 这一并发症，并可能为其他神经血管提供侧枝洞察 糖尿病的并发症。 建议的实验非常适合于满足本RFA的目标 由于新的和创新的技术被用来推动我们的当前 了解泌尿生殖器官发育的一个方面，特别是如何神经 阴茎出生后形态发生过程中的Shh信号建立下体 勃起所需的海绵体完整性。重新建立该信令 PATH为勃起功能障碍的治疗提供了巨大的希望。知识 在这些研究中获得的结果可用于研究神经输入的作用 在建立组织特性和检查神经病变的功能方面 疾病。

DESCRIPTION (provided by applicant): The proposed research will examine the role of Sonic hedgehog (Shh) in penile development and the dysregulation of this pathway in diabetes induced erectile dysfunction. Shh is a secreted glycopeptide that is critically relevant in mesenchymal-epithelial interaction in developing tissues. We will show preliminary evidence that Shh signaling in the corpora is neurally regulated during penile development and in the adult, and propose to determine the impact of diabetic neuropathy on the expression and activity of Shh in corporal bodies. Diabetes mellitus is a common risk factor for erectile dysfunction, which is a devastating pathologic development that effects 10-30 million American men and costs in excess of $150 million for inpatient urologic care alone (1985 dollars). Although angiopathy and neuropathy are frequent complications in the natural history of DM, the precise cause of diabetic impotence remains unknown. We will examine the hypothesis that neural Shh signaling is elemental in establishing and maintaining normal penile morphology and that erectile dysfunction associated with diabetic neuropathy results from disruption of the homeostatic functions of the Shh pathway. The power of this proposal is its potential to provide novel and critically important insight into the mechanism of diabetes induced erectile function. This may provide the basis for new treatments to prevent or treat this complication and may provide collateral insights into other neurovascular complications of diabetes. The proposed experiments are ideally suited to satisfy the goals of this RFA since novel and innovative technology is utilized to advance our current understanding of one aspect of urogenital development, specifically how neural Shh signaling during postnatal morphogenesis of the penis establishes corporal cavernosal integrity required for erection. Re-establishment of this signaling pathway offers great promise for erectile dysfirnction treatment. Knowledge gained in these studies may be applied to investigate the role of neural input in establishing tissue identity and examining the function of neuropathy in disease.