TRANSCRIPTION FACTORS REGULATING PALATOGENESIS

颅面发育缺陷导致腭裂和/或唇裂的比例超过千分之一。颅面发育的分子机制的调查将导致改善诊断，治疗和预防这些出生缺陷。该项目的长期目标是了解转录因子Zfhep在颅面发育中的作用。在小鼠中靶向破坏Zfhep/deltaEF-1基因可导致继发性腭裂、Meckel软骨肥大和围产期死亡。然而，目前尚不清楚这些面部缺陷是否是由于Zfhep直接或间接参与发育所致。确定Zfhep的时空表达是确定它是否在颅面发育中具有直接作用的重要一步。该项目的具体目标是确定Zfhep-1和Zfhep-2的表达模式在间充质和上皮的腭，并在Meckel的软骨在小鼠发育过程中使用原位杂交和免疫组化。我们还将研究Zfhep在牙芽发育过程中的表达。我们将确定在Meckel软骨发育过程中表达Zfhep的特定细胞类型（前软骨细胞、软骨细胞或肥大软骨细胞）。该R 03应用的结果将提供颅面发育期间Zfhep的时间和空间表达模式的完整图片，并证明Zfhep可以对发育产生直接影响。后续工作将研究颅面发育过程中Zfhep作用的分子机制。

Defects in craniofacial development to cleft palate and/or cleft lip in more than 1 out of 1,000 births. Investigation of the molecular mechanisms of craniofacial development will lead to improved diagnosis, treatment, and prevention of these birth defects. The long term objective of this project is to understand the role of the transcription factor Zfhep in craniofacial development. Targeted disruption of the Zfhep/deltaEF-1 gene in mice created cleft secondary palate, hypertrophy of Meckel's cartilage, and perinatal death. However, it is unknown whether these facial defects are due to a direct, or indirect involvement of Zfhep in development. Defining the temporal-spacial expression of Zfhep is an essential step towards determining whether it has a direct role in craniofacial development. The specific goals of this project are to determine the expression pattern of both Zfhep-1 and Zfhep-2 in the mesenchyme and epithelium of the palate, and in Meckel's cartilage during mouse development using both in situ hybridization and immunohistochemistry. We will also investigate the expression of Zfhep during development of tooth buds. We will determine the specific cell types (pre-chrondrocytes, chrondrocytes, or hypertrophy chrondrocytes) expressing Zfhep during development of Meckel's cartilage. The results of this R03 application will provide a complete picture of the temporal and spatial expression pattern of Zfhep during craniofacial development, and demonstrate where Zfhep can have direct effects on development. Subsequent work will investigate the molecular mechanism(s) of Zfhep action during craniofacial development.