TRANSCRIPTION FACTORS REGULATING PALATOGENESIS

颅面发育缺陷导致腭裂和/或唇裂的几率超过千分之一。颅面发育的分子机制的研究将有助于改善这些出生缺陷的诊断、治疗和预防。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基因会导致继发腭裂、梅克尔软骨肥大和围产期死亡。然而，尚不清楚这些面部缺陷是由于Zfhep在发育过程中的直接或间接参与。确定Zfhep的时空表达是确定其是否在颅面发育中起直接作用的重要一步。本项目的具体目标是利用原位杂交和免疫组织化学方法确定小鼠发育过程中Zfhep-1和Zfhep-2在腭间质和上皮以及Meckel软骨中的表达模式。我们还将研究Zfhep在牙芽发育过程中的表达。我们将确定在梅克尔软骨发育过程中表达Zfhep的特定细胞类型（前时细胞、时细胞或肥大时细胞）。本次R03应用的结果将提供完整的Zfhep在颅面发育过程中的时空表达模式，并证明Zfhep在哪些地方可以对发育产生直接影响。后续工作将研究Zfhep在颅面发育过程中的分子机制。

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.