Tmem132a, a single-pass type I transmembrane protein, is a crucial regulator in multiple biological processes. It is involved in the Wnt/β-catenin signaling pathway, which is essential for embryonic development and adult tissue homeostasis [2,5]. It also interacts with planar cell polarity (PCP) regulators, indicating its role in PCP-related processes [1].

In Tmem132a mutant mice, various caudal developmental defects are observed. These include skeletal, posterior neural tube closure, genitourinary tract, and hindgut defects. Specifically, in mutant embryos, the visceral endoderm fails to be excluded from the medial region of the early hindgut, leading to malformations of cloaca-derived structures and indirectly causing neural tube and kidney/ureter defects [1]. Tmem132a-null mice also show disrupted spinal neural tube closure and lateral migration of the caudal paraxial mesoderm, as TMEM132A regulates integrins and downstream integrin pathway activation [3]. In addition, mouse embryos lacking Tmem132a display malformations similar to Wnt/β-catenin mutants, and knockdown in cultured cells suppresses canonical Wnt/β-catenin signaling [2]. In gastric cancer cells, knockdown of Tmem132A restrains cell proliferation, migration, and invasion via inhibiting Wnt signaling [4].

In conclusion, Tmem132a plays a vital role in embryonic development, especially in hindgut morphogenesis, caudal development, and neural tube closure, mainly through its regulation of the Wnt/β-catenin signaling pathway and PCP. Studies using Tmem132a KO mouse models have provided valuable insights into the molecular mechanisms underlying these processes and their associated diseases, such as caudal developmental defects and certain cancers [1-4].

References:

1. Zeng, Huiqing, Liu, Aimin. 2023. TMEM132A regulates mouse hindgut morphogenesis and caudal development. In Development (Cambridge, England), 150, . doi:10.1242/dev.201630. https://pubmed.ncbi.nlm.nih.gov/37390294/

2. Oh, Shin Ae, Jeon, Jiyeon, Je, Su-Yeon, Jung, Joohyun, Ko, Hyuk Wan. 2024. TMEM132A regulates Wnt/β-catenin signaling through stabilizing LRP6 during mouse embryonic development. In Cell communication and signaling : CCS, 22, 482. doi:10.1186/s12964-024-01855-9. https://pubmed.ncbi.nlm.nih.gov/39385148/

3. Li, Binbin, Brusman, Liza, Dahlka, Jacob, Niswander, Lee A. 2022. TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration. In Development (Cambridge, England), 149, . doi:10.1242/dev.200442. https://pubmed.ncbi.nlm.nih.gov/35950911/

4. Gao, Qianqian, Chen, Yufang, Yue, Lingping, Li, Ziyan, Wang, Meihua. 2022. Knockdown of TMEM132A restrains the malignant phenotype of gastric cancer cells via inhibiting Wnt signaling. In Nucleosides, nucleotides & nucleic acids, 42, 343-357. doi:10.1080/15257770.2022.2148692. https://pubmed.ncbi.nlm.nih.gov/36441075/

5. Li, Binbin, Niswander, Lee A. 2020. TMEM132A, a Novel Wnt Signaling Pathway Regulator Through Wntless (WLS) Interaction. In Frontiers in cell and developmental biology, 8, 599890. doi:10.3389/fcell.2020.599890. https://pubmed.ncbi.nlm.nih.gov/33324648/