Developmental mechanisms of evolution: loss of reproductive structures in birds

调控泌尿生殖系统（生殖和泌尿系统）发育的遗传机制是发育生物学中最不为人所知的。矛盾的是，外生殖器的出生缺陷是人类最常见的畸形之一，仅次于心脏缺陷。人类一些最常见的生殖器畸形——比如开放的尿道和持续的泄殖腔（泌尿道和消化道的单一出口）——类似于脊椎动物的自然变异。因此，确定非哺乳脊椎动物泌尿生殖系统发育的直接机制将对我们理解人类泌尿生殖系统异常发育具有重要意义。此外，比较发育研究将确定驱动进化变化的遗传机制。该项目研究了鸟类外生殖器进化的发育基础，鸟类展示了广泛的解剖模式，从几乎像哺乳动物一样的阴茎到完全没有外生殖器。该方法将结合分子、细胞和实验胚胎学方法来确定调节生殖发育的遗传回路在鸟类和哺乳动物之间的保守程度。人们预计，指导哺乳动物生殖器发育的遗传程序也适用于最原始的鸟类，这将表明，一种被认为是哺乳动物独有的特征有着令人惊讶的深层起源。此外，据预测，在一种特定的鸟类（被称为鸟形目）中，由于一种古老的细胞生存机制被破坏，导致外生殖器无法形成，而过度的细胞死亡会导致发育停滞。需要使用非传统模型系统（如鸟类和爬行动物）进行比较研究，以开发新的疾病模型，该项目将为研究界提供这种基础设施。考虑到啮齿动物模型的成本过高，在资源有限的小型学院和国家的许多研究人员，鉴定新的禽（鸟）胚胎模型尤为重要。拟议活动的影响超出了科学发现的范围。通过确定进化变化的实际机制，这项研究将有助于社会对进化如何工作的理解，这将提高我们国家对进化的认识。该项目与涉及从小学到大学生的教育推广活动相配合，并包含具体的行动项目，以增加妇女和其他在科学领域代表性不足的群体的参与。

The genetic mechanisms that regulate development of the genitourinary system (reproductive and urologic organs) are among the least understood in developmental biology. Paradoxically, birth defects of the external genitalia are among the most frequently occurring malformations in humans, ranking second only to heart defects. Some of the most common genital malformations in humans -- such as an open urethral tube and a persistant cloaca (a single outlet for urinary and digestive tracts) -- resemble the natural variation seen across vertebrates. Thus, identification of the mechanisms that direct genitourinary development in non-mammalian vertebrates will have implications for our understanding of abnormal genitourinary development in humans. Moreover, comparative developmental studies will identify the genetic mechanisms that drive evolutionary change. This project investigates the developmental basis of external genital evolution in birds, a group that exhibits a broad spectrum of anatomical patterns that range from an almost mammal-like phallus to complete absence of external genitalia. The approach will combine molecular, cellular, and experimental embryological methods to determine the extent to which the genetic circuits that regulate genital development are conserved between birds and mammals. It is expected that the genetic program that directs genital development in mammals also operates in the most primitive birds, which would point to a surprisingly deep origin of a character that had been thought to be exclusive to mammals. In addition, it is predicted that in a specific group of birds (known as the galliformes), failure to form external genitalia results from disruption of an ancient cell survival mechanism, and excessive cell death causes a developmental arrest. Comparative studies using non-traditional model systems, such as birds and reptiles, are needed to develop new models for disease, and this project will contribute this infrastructure to the research community. Identification of new avian (bird) embryo models is especially important given the prohibitive cost of rodent models for many researchers at small colleges and in countries with limited resources. The impacts of the proposed activities extend beyond scientific discovery. By identifying actual mechanisms of evolutionary change, this research will contribute to society's understanding of how evolution works, which will improve our national literacy in evolution. The project dovetails with educational outreach activities involving students from elementary school to undergraduates, and contains specific action items to increase participation of women and other groups underrepresented in science.