Celsr1-flox Mouse

CELSR1, short for cadherin EGF LAG seven-pass G-type receptor 1, is an atypical cadherin that belongs to the adhesion GPCR family. It plays multiple essential functions in epithelia and the nervous system, with a key role in epithelial planar cell polarity (PCP) [1,3]. It is also involved in neurodevelopment as it is mainly expressed in neural stem cells during the embryonic period [2].

In mouse models, Celsr1 mutants have provided insights into its functions. For instance, in Celsr1-deficient mice, facial branchiomotor neurons inappropriately migrate rostrally, indicating that Celsr1 suppresses Wnt5a-mediated chemoattraction to prevent incorrect neuron migration [4]. Also, knockout of Celsr1 alone abolishes epidermal PCP, showing its major role in this process compared to Celsr2 [5]. In addition, CELSR1 variants identified in human studies are associated with partial epilepsy of childhood, suggesting its potential as a candidate pathogenic gene [2]. In congenital heart disease, CELSR1 is a susceptibility gene for familial bicuspid aortic valve and hypoplastic left heart syndrome, implicating PCP pathway perturbation [6].

In conclusion, CELSR1 is crucial for PCP and neurodevelopment. Mouse knockout models have been instrumental in revealing its role in neuronal migration. Its association with diseases such as epilepsy and congenital heart disease from human genetic studies further emphasizes its importance in understanding disease mechanisms.