En1, short for Engrailed-1, is a homeobox transcription factor. It is involved in multiple biological processes such as neuronal development in the midbrain, cerebellum, hindbrain and spinal cord [5]. It has also been associated with signaling pathways like Wnt and Hedgehog, which play crucial roles in development and disease [2,3,4]. Genetic models, such as mouse models, are valuable tools for studying its functions.

In a mouse model (En1(cre/flox)), conditional loss of En1 led to low bone mass, likely due to high bone turnover, indicating its role in determining bone density and fracture risk [1]. In another study on superior olivary complex (SOC) neurons, En1 deletion caused aberrant neuron positioning and subsequent death, along with failure to express FoxP1, highlighting its importance in the development and maturation of these neurons [5].

In conclusion, En1 is essential for normal development of multiple tissues, including bones and neurons. Mouse models, especially those with gene knockout or conditional knockout, have been instrumental in revealing its functions in bone density regulation and neuron development. These findings may have implications for understanding and treating diseases related to bone density and central auditory neuron disorders.

References:

1. Zheng, Hou-Feng, Forgetta, Vincenzo, Hsu, Yi-Hsiang, Rivadeneira, Fernando, Richards, J Brent. 2015. Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture. In Nature, 526, 112-7. doi:10.1038/nature14878. https://pubmed.ncbi.nlm.nih.gov/26367794/

2. Alves dos Santos, Maria T M, Smidt, Marten P. 2011. En1 and Wnt signaling in midbrain dopaminergic neuronal development. In Neural development, 6, 23. doi:10.1186/1749-8104-6-23. https://pubmed.ncbi.nlm.nih.gov/21569278/

3. Peluffo, Guillermo, Subedee, Ashim, Harper, Nicholas W, Carroll, Jason S, Polyak, Kornelia. 2019. EN1 Is a Transcriptional Dependency in Triple-Negative Breast Cancer Associated with Brain Metastasis. In Cancer research, 79, 4173-4183. doi:10.1158/0008-5472.CAN-18-3264. https://pubmed.ncbi.nlm.nih.gov/31239270/

4. Chang, Jinchun, Guo, Chenjia, Li, Jianyu, Chen, Jian, Huang, Song. 2022. EN1 Regulates Cell Growth and Proliferation in Human Glioma Cells via Hedgehog Signaling. In International journal of molecular sciences, 23, . doi:10.3390/ijms23031123. https://pubmed.ncbi.nlm.nih.gov/35163043/

5. Altieri, Stefanie C, Jalabi, Walid, Zhao, Tianna, Romito-DiGiacomo, Rita R, Maricich, Stephen M. 2015. En1 directs superior olivary complex neuron positioning, survival, and expression of FoxP1. In Developmental biology, 408, 99-108. doi:10.1016/j.ydbio.2015.10.008. https://pubmed.ncbi.nlm.nih.gov/26542008/