Pbx4, a member of the Pre-B cell leukaemia transcription factor family, plays significant roles in diverse biological processes. It acts as a transcriptional cofactor of HOX proteins and is involved in pathways related to development and disease [3]. Its biological importance spans from embryonic development to cancer-related processes [2,3]. Genetic models, especially knockout mouse models, have been crucial in uncovering its functions [1].

In Pbx4 knockout (KO) mice, growth retardation, premature death, shorter hindlimbs, and lower numbers of reticulocytes and lymphocytes were observed, indicating its role in limb development and haematopoiesis [1]. In zebrafish, Pbx4-deficient mutants showed enlarged hearts due to improper specification and proliferation of second heart field progenitors, highlighting its role in heart development [4]. Zebrafish pbx4 mutant embryos also had a delayed onset of myocardial differentiation [5].

In conclusion, Pbx4 is essential for processes such as limb development, haematopoiesis, and heart development as revealed through model-based research. In the context of diseases, it has been associated with colorectal cancer, where its overexpression is related to a worse survival rate, suggesting its potential as an oncopromoter [2]. The study of Pbx4 KO models has provided valuable insights into these specific disease-related roles.

References:

1. Ning, Yan, Duo, Shuguang, Lin, Xiwen, Liu, Xiaowei, Han, Chunsheng. 2024. Transcription factor PBX4 regulates limb development and haematopoiesis in mice. In Cell proliferation, 57, e13580. doi:10.1111/cpr.13580. https://pubmed.ncbi.nlm.nih.gov/38230761/

2. Martinou, Eirini G, Moller-Levet, Carla S, Angelidi, Angeliki M. 2022. PBX4 functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the PBX gene family. In American journal of cancer research, 12, 585-600. doi:. https://pubmed.ncbi.nlm.nih.gov/35261789/

3. Song, Yipeng, Ma, Rongna. 2022. Identifying the Potential Roles of PBX4 in Human Cancers Based on Integrative Analysis. In Biomolecules, 12, . doi:10.3390/biom12060822. https://pubmed.ncbi.nlm.nih.gov/35740947/

4. Holowiecki, Andrew, Linstrum, Kelsey, Ravisankar, Padmapriyadarshini, Salomonis, Nathan, Waxman, Joshua S. 2020. Pbx4 limits heart size and fosters arch artery formation by partitioning second heart field progenitors and restricting proliferation. In Development (Cambridge, England), 147, . doi:10.1242/dev.185652. https://pubmed.ncbi.nlm.nih.gov/32094112/

5. Kao, Robert M, Rurik, Joel G, Farr, Gist H, Majesky, Mark W, Maves, Lisa. . Pbx4 is Required for the Temporal Onset of Zebrafish Myocardial Differentiation. In Journal of developmental biology, 3, 93-111. doi:. https://pubmed.ncbi.nlm.nih.gov/26770887/