TRANSCRIPTION FACTORS REGULATING PALATOGENESIS

在1000名新生儿中，有超过1名的新生儿存在颅面发育缺陷，导致腭裂和/或唇裂。研究颅面发育的分子机制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在头面部发育中的作用。Zfhep/deltaEF-1基因的靶向破坏在小鼠身上造成继发性腭裂、Meckel‘s软骨肥大和围产儿死亡。然而，目前尚不清楚这些面部缺陷是由于Zfhep直接还是间接参与了发育。确定Zfhep的时空表达是确定它是否在头面部发育中起直接作用的关键一步。该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Zfhep-1和Zfhep-2在小鼠发育过程中间充质和上皮以及Meckel‘s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Meckel‘s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)。这个R03应用的结果将提供Zfhep在头面部发育过程中的时间和空间表达模式的完整图景，并展示Zfhep在哪里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(S)。

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.